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CT studies in prostate cancer patients
Physica Medica 30 (2014) 346e351
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Original paper
Radiation dosimetry of cancer patients
18
F-flurocholine PET/CT studies in prostate
Cinzia Fabbri a, *, Riccardo Galassi c, Andrea Moretti c, Emanuele Sintuzzi b, Valentina Mautone b, Graziella Sarti d, Lidia Strigari e, Marcello Benassi a, Federica Matteucci b a
Medical Physics Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, FC, Italy Nuclear Medicine Unit, IRCCS IRST, Meldola, FC, Italy Nuclear Medicine Unit, Pierantoni-Morgagni Hospital, Forlì, FC, Italy d Medical Physics Unit, Bufalini Hospital, Cesena, FC, Italy e Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, IFO, Rome, Italy b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 22 April 2013 Received in revised form 20 October 2013 Accepted 25 October 2013 Available online 13 November 2013
Purpose: We aimed to evaluate the Equivalent Doses (HTs) to highly exposed organs as well as the Effective Dose (ED) for 18F-fluorocholine PET/CT scan in the follow-up of prostate cancer patients. Methods: Fifty patients were administered with 18F-fluorocholine. The activities in organs with the highest uptake were derived by region-of-interest (ROI) analysis. OLINDA/EXM1.0 and Impact software were used to assess ED for the administered 18F-fluorocholine and CT scan, respectively, and the 18Ffluorocholine and CT-scan EDs summed to yield the total ED for the PET/CT procedure. Results: The calculated 18F-fluorocholine and CT scans EDs based on ICRP Publication 103 were 5.2 mSv/ 300 MBq and 6.7 mSv, respectively. The 18F-fluorocholine HTs to the liver, kidneys, spleen and pancreas were about threefold higher than those from the CT, which contributed a greater proportion of the total ED than the 18F-fluorocholine did. Conclusions: For 18F-fluorocholine PET/CT procedures, about 40% of the ED is contributed by administered 18F-fluorocholine and 60% by the CT scan. The kidneys and liver were the highly exposed organs. Considering the large number of diagnostic procedures oncology patients undergo, radiation dosimetry is important in relation to the stochastic risk of such procedures. Ó 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
Keywords: 18 F-Fluorocholine PET/CT imaging Dosimetry Effective dose Equivalent dose Biodistribution
Introduction Administration of radiotracers to human subjects exposes them to a stochastic risk that needs to be carefully evaluated. The International Commission on Radiological Protection (ICRP) Recommendations take into account the detriment from the exposure of different organs to low doses of radiation through tissue weighting factors (wTs) that represent the relative contributions of individual organs and tissues to total detriment. The ICRP103 Recommendations [1] replaced the weighting factors published in ICRP60 [2] with substantially modified values and introduced the official computational models representing the adult Reference Male and
* Corresponding author. Medical Physics Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, FC, Italy. Tel.: þ39 3394899467. E-mail address: [email protected] (C. Fabbri).
Reference Female used in establishing radiation protection guidance [3]. Research protocols involving the clinical use of new radiotracers, such as 18F-fluorocholine, should include estimation of normal organ absorbed doses (particularly for high-uptake organs) and of the ED. In Europe, although there is no dose limit for research purposes, the ED must be evaluated and justified with respect to the calculated risk for the patient. On the other hand, the USA Food and Drug Administration for certain types of clinical research studies places limits per organ per study (generally 50 mSv, with the exception of red marrow, gonads and lens of the eye, for which 30 mSv are recommended). Moreover, while hybrid imaging techniques such as SPECT/CT and PET/CT scans allow a better diagnostic evaluation based on functional and morphological information, they deliver an ED to the patient due to internal energy deposition from radiopharmaceutical administration and external irradiation from CT X-rays. In order to optimally balance the
1120-1797/$ e see front matter Ó 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejmp.2013.10.007
C. Fabbri et al. / Physica Medica 30 (2014) 346e351
stochastic risk of diagnostic procedures [4e6] with the medical information being sought, it is important to optimize such procedures in terms of the CT parameters as well as the administered activity of the radiopharmaceutical. It should be noted that the ED is defined by ICRP for a generic reference individual and in practice it cannot actually be evaluated for individual patients. Our work contributes dosimetric data for 18F-fluorocholine used for the detection of local and distant recurrence of prostate cancer and focuses on the absorbed dose to normal organs with higher uptakes. Materials and methods
347
wherein, a very fast distribution of the radiotracer was reported in organs and lesions (by 10 min p.i.), confirming the imaging acquisition at 50 min as representative of the near-steady state distribution of the radiotracer.
~ðrS ; TD Þ ¼ 1:44*t1=2p * a
OrganðrS Þtotal activity Injected activity
(1)
where rs ¼ source organ t1/2p ¼ physical half time TD ¼ N
Patients The 18F-fluorocholine PET/CT studies were approved by the local Ethics Committee and activated in our institute in October 2011. To date about 200 patients with prostate cancer have been enrolled in the study, of whom 50 were included in the dosimetric evaluations. Patients had previously undergone prostatectomy or radiotherapy with curative intent and a 18F-fluorocholine PET/CT scan was scheduled to screen for local and distant recurrence after an increase in prostate specific antigen (PSA > 1 ng/ml). Patients were injected with about 4 MBq/kg of 18F-fluorocholine (Advanced Accelerator Applications S.A., Saint Genis Pouilly, France). Imaging: acquisition, reconstruction and elaboration Imaging was performed in 2D-mode using a Discovery LS PET/ CT scanner (General Electric Medical System, Milwaukee, WI), with well-counter calibration updated every three months. The fullwidth at half maximum (FWHM) spatial resolution was 5 mm in each direction and 2D-mode sensitivity was 7.1 cps/Bq/cc, determined according to NEMA NU 2-1994 [7]. The volumetric computed tomography dose index (CTDIv) of the clinical protocol visible on the screen of the CT console was compared with the measured CTDIv by specific phantom tests; the agreement was good, with a percentage difference of less than 4%. Whole-body PET images were acquired 50 min post-injection (p.i.) from the nose to the mid-thigh (6e7 bed positions, 3e3.5 min/ bed). CT acquisition parameters were as follows: 120 kV, 90 mA, 0.75e1.5 pitch, 0.8 s/rot, 20 mm collimation, 5 mm slice thickness. PET data were corrected for scatter, randoms, dead time and decay and images were reconstructed using a 2D Ordered-SubsetsExpectation Maximization (OSEM) iterative reconstruction algorithm (2 iterations, 28 subsets). Image analysis was carried out using Xeleris1 GE software. In particular, ROIs of 2 cm in diameter were drawn within each source organ on three/four slices selected at the top, in the middle and at the bottom of the organ and the mean value of the Standard Uptake Value calculated with body weight (SUVbw) on the three/four slices of each organ was calculated. The source regions were bone, fat, kidneys, liver, lungs, muscle, pancreas, salivary glands (parotids and submandibular glands), spleen, small intestine and testes. Moreover, in a group of 18 patients we performed also an early acquisition (within 5 min p.i.) in order to evaluate the uptake kinetics in the highly exposed organs (kidneys, liver and spleen). Biodistribution and dosimetric study The mean activity concentration (kBq/ml) and the percentage of injected activity (%IA) for all 50 patients were obtained for each organ at 50 min p.i. The time integrated-activity coefficients [8], ã(rS, TD), were calculated assuming no biologic removal, tb ¼ N (equation (1)) according to data from a number of studies [9,10]
Furthermore, for the 18 patients with acquisitions at 5 and 50 min p.i. the time integrated-activity coefficients were calculated in kidneys, spleen and liver by applying the trapezoidal rule [11] and with physical decay only assumed for integration from 50 min on. The above values were compared in term of percentage difference with those obtained by assuming no biological removal. The calculation of the total organ activity was determined taking into account the organ reference masses and the standard-man total body mass of the reference male and the standard uptake value [12]. We used OLINDA/EXM1.0 software to calculate the equivalent doses, HTs (mSv/MBq), entering the ã(rS, TD) of each source organ (liver, lungs, kidneys, muscle, pancreas, small intestine, spleen, testes, red marrow, urinary content and remainder-of-body) and using the sphere model to obtain the HT for salivary glands. The mass of the parotid glands was assumed equal to 50 g and the mass of the submandibular glands 25 g [13]. The ã(rS, TD) of blood and urinary bladder contents reported in the literature [14,15] was used to calculate the HT for red marrow and urinary bladder wall, respectively, since it was not possible to collect and count samples of blood and urine. A bladder voiding interval of 1 h was assumed [14,15] and because of the absence of specific uptake in the bones and red marrow, red marrow time integrated-activity coefficient was calculated by the blood-based method (which assumes a linear relation between the blood and red marrow time integratedactivity coefficient). The proportionality factor was the ratio between standard-man red marrow mass and standard-man blood mass. ED (mSv/MBq) was calculated by summing the products of the organ equivalent doses HTs and their respective organ weighting factors and adding the remainder-of-body ED contribution according to the different calculation algorithms and wTs proposed in ICRP60 [2] and ICRP103 Recommendations [1]. In particular, to determine the remainder-of-body ED contribution as stated in ICRP103, the remainder tissues mean HT was multiplied for the relative wT equal to 0.12 [2]. Instead, to obtain the remainder-ofbody ED contribution according to the ICRP Publication 60, in those exceptional cases in which one single organ of the remainder (in our specific case the kidney) receives an equivalent dose in excess of the highest dose in any of the twelve organs (or tissues) for which a wT is specified [1], a weighting factor of 0.025 was applied to that organ (kidney) and a weighting factor of 0.025 to the average dose calculated among the other organs of the remainder. The comparison was performed in order to evaluate possible significant differences, in terms of percentage differences, calculated as showed in equation (2), between the ED values based on ICRP Recommendations 103 and 60 [1,2].
%DIFFðEDICRP60 vs EDICRP103 Þ ¼
EDICRP60 EDICRP103 *100 EDICRP103
(2)
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C. Fabbri et al. / Physica Medica 30 (2014) 346e351
Figure 1. 18F-Fluorocholine PET/CT of patient submitted to prostatectomy, 71 years old, 100 kg, PSA 1.92 ng/ml, injected with 253 MBq. A) 5 min p.i., B) 50 min p.i. Although both images show pathological uptake in skeletal and lymph node sites, the early image has higher background activity.
The ED-based on ICRP103 tissue weighting factors was calculated using an EXCEL algorithm, since only ICRP60 weighting factors are used in OLINDA/EXM1.0 software for the calculation of the ED. In addition, the ED of the CT scan was evaluated by inserting the acquisition parameters of a standard examination into Impact software (www.impactscan.org), which gave us the opportunity of analyzing data taking into consideration both ICRP60 and ICRP103 weighting factors. Table 1 SUVbw mean values of organs obtained from 18F-fluorocholine PET/CT images of 50 patients acquired 50 min p.i. Organs
SUVbw SD
Bladder Bone (healthy femur) Subcutaneous fat Kidney parenchyma Liver Lungs Skeletal muscle (gluteus muscle) Pancreas Parotid glands Small intestine Spleen Submandibular glands Testes
15.9 18.5 0.8 0.6 0.3 0.2 13.1 3.6 9.7 2.5 1.0 0.3 1.0 0.4 8.1 2.1 6.4 1.9 2.1 0.9 4.7 0.9 6.9 2.1 0.9 0.3
Results Effective dose from PET scan The mean age of this group of patients was 71 years (range 45e 92) and mean weight was 84 kg (range 58e110). The mean activity injected was 3.3 MBq/kg (range 1.8e4.4). Figure 1 shows two images acquired A) 5 min and B) 50 min p.i. (253 MBq) of a 71-year-old patient who had previously undergone prostatectomy. PSA was 1.92 ng/ml and weight was 100 kg. CTDIv was equal to 7.5 mSv with120 kV and 140 mA as acquisition parameters. Both images demonstrated 18F-fluorocholine pathological uptake in skeletal and lymph node sites, although in the early image (A) a greater background activity and a higher activity concentration in the urinary system were evident. Table 1 shows the mean values and standard deviation (SD) of the SUVbw of the 50 patients at 50 min p.i.; the highest values were found in the bladder, kidneys, liver, pancreas, salivary glands and spleen. Table 2 shows the time-integrated activity coefficients ã(rS, TD) for the source organs relative to IRST patients (column 2) with respect to those reported by Giussani for the Reference Patient (column 3) [16], Janzen (column 4) [14,15], Nosske and Brix (column 5) [17] and DeGrado (column 6) [9]. Table 3 reports the ã(rS, TD) calculated by the trapezoidal rule (column 2) and by assuming no biological removal (column 3) in 18
C. Fabbri et al. / Physica Medica 30 (2014) 346e351 Table 2 Time-integrated activity coefficients ã(rS, TD) (h) (no biological removal, tb ¼ N) relative to IRST pts (column 2) compared with those presented for the reference patient by Giussani [16] (column 3), Janzen [14,15] (column 4), Nosske and Brix [17] (column 5) and DeGrado [9,19] (column 6). Organ
IRST 2012
Giussani Janzen Nosske and DeGrado 2012 2011 Brix 2009 2002
Liver 0.652 0.140 Spleen 0.031 0.006 Pancreas 0.027 0.007 Kidneys 0.142 0.039 Small intestine 0.047 0.019 Lungs 0.038 0.014 Testes 0.0013 0.0006 Parotid glands 0.011 0.0035 Submandibular 0.0064 0.0018 glands Muscle 0.984 0.377 Urinary bladder e contents Blood Remainder-of-body 0.576 a b c
0.422 0.022 e 0.114 e e e e e
0.410 0.024 e 0.120 e e e e e
0.37 0.053 e 0.24 e e e e e
0.142 0.0297 e 0.219 e e e e e
e 0.039a 0.119b 0.270 1.621
e 0.043a
e 0.078b
e 0.048c
0.344 1.569
1.87 e
Bladder voiding interval, 1 h. Bladder voiding interval, 3.5 h. Dynamic bladder voiding was not used.
patients with acquisitions at 5 and 50 min p.i. The percentage difference (%DIFF ¼ (ã(rS, TD)trap ã(rS, TD)tb¼N)/ã(rS, TD)tb¼N) was within 2% for kidneys and spleen and 3% for liver. Table 4 shows the mean values of HT for our patients (column 2) together with the HT values published by Giussani for a Reference Patient (column 3) [16], Janzen (column 4) [14,15], Nosske and Brix (column 5) [17] and DeGrado (column 6) [9,19]. Table 5 shows the wT for organs and their contribution (wT*HT) to the EDPET. As not all target organs were included in our evaluation, the sum of wT was 0.95 for ICRP103 and 0.94 for ICRP60 [18]. Therefore, we multiplied the mean value of equivalent dose, HT, relative to the total body and provided by OLINDA/EXM1.0 software (Table 4), by the wT of the organs not included in our analysis in order to obtain the final estimate of EDPET. The total contribution of the organs listed in Table 6 to the EDPET was 14.2 mSv/MBq and 12.7 mSv/MBq calculated by ICRP60 and ICRP103, respectively, while the contribution of the remainder of body was 3.6 mSv/MBq (ICRP60) and 4.6 mSv/MBq (ICRP103), respectively. The highest percentage differences (ICRP60 vs ICRP103) were 22% for the contribution of the Remainder of body to the EDPET and þ12% for the contribution of the organs (Table 6). Finally, the impact on the total EDPET of the different wTs was about þ3%. It is noteworthy that the liver was the organ that contributed the highest percentage (24%) to the EDPET. Effective dose from CT scan Figure 2 shows the distribution of the CTDIv (mSv) values vs patient mass (kg). The dashed line is the median CTDIv value (5.4 mSv). The mean value of CTDIv was 6.3 mSv (range 3.2e15 mSv). Table 3 Time-integrated activity coefficients ã(rS, TD) (h) relative to kidneys, spleen and liver in a group of 18 patients calculated by the trapezoidal rule (column 2) and by assuming no biological removal (tb ¼ N) (column 3). Organ
kidneys Spleen Liver
Time-integrated activity coefficients ã(rS, TD), (h)
Time-integrated activity coefficients ã(rS, TD), (h)
Trapezoidal rule
No biological removal (tb ¼ N)
0.175 0.056 0.035 0.008 0.602 0.175
0.171 0.055 0.035 0.009 0.620 0.184
349
Table 4 Mean values of equivalent doses, HTs, calculated for our cohort of 50 patients (column 2) compared to the reference patient from Giussani (column 3) [16], Janzen (column 4) [14,15], Nosske and Brix (column 5) [17] and DeGrado (column 6) [9,19]. HT [mSv/MBq 102] Organs
IRST
Giussani
Janzen
NosskeeBrix
DeGrado
Liver Spleen Pancreas Kidneys Small intestine Lungs Testes Muscle Urinary bladder wall Adrenal glands Brain Breast Gallbladder wall Colon wall Stomach wall ULI wall Heart wall Osteogenic cells Skin Thymus Thyroid Red marrow Salivary glands Total body
8.49 4.07 6.29 9.66 1.92 1.42 1.02 1.18 2.77 1.76 0.42 0.58 2.27 0.91 1.15 1.23 1.07 1.23 0.52 0.74 0.65 1.42 4.2 1.25
5.6 3.0 1.6 7.8 1.3 1.1 0.93 1.0 2.9 1.7 0.82 0.85 e 1.3 1.3 e e e 0.78 1.0 0.95 1.0 e
6.2 4.2 e 8.3 e e e e 1.7 e e e e e e e e e e e e e e e
5.1 6.3 e 15 e e e e 4.7 e e e e e e e e e e e e e e e
5.16 4.73 e 14.8 2.1 1.03 1.05 1.0 3.32 e e e e e e e e e e e 1.32 1.54 e e
It must be pointed out that the highest values belong to the first enrolled patients when CT acquisition parameters, in particular mA, were set at a higher level. Subsequently, as the most frequent site of recurrence is the bone or lymph nodes, the physicians decided that it was feasible to accept a slight reduction in the quality of images, resulting in dose-sparing for patients. The ED of the CT scan was 6.8 mSv and 6.7 mSv based on ICRP60 and ICRP103 wTs, respectively. Table 7 shows the mean values of HT PET, HT CT and their sum (HT 18 F-fluoPETþCT) for the organs showing the highest uptake of rocholine. Interestingly, the dose equivalent values for the kidneys, liver and pancreas from the PET scan were about threefold higher than those from the CT scan. Discussion and conclusion The present study investigated the organ equivalent doses, HTs and the effective dose, ED, based on a ROI analysis of images obtained in a large cohort of patients who underwent 18F-fluorocholine PET/CT diagnostic procedures to screen for local and distance recurrence after increase of PSA. Table 5 wT*HT of the organs calculated by applying wT from ICRP60 [1] and ICRP103 [2]. Organs Testes Red bone marrow Colon Lungs Stomach Bladder Breast Liver Thyroid Skin Salivary glands Brain
wT ICRP60
wT ICRP103
wT*HT ICRP60 [mSv/MBq]
wT*HT ICRP103 [mSv/MBq]
0.20 0.12 0.12 0.12 0.12 0.05 0.05 0.05 0.05 0.01 e e
0.08 0.12 0.12 0.12 0.12 0.04 0.12 0.04 0.04 0.01 0.01 0.01
2.04 1.70 1.09 1.70 1.38 1.39 0.29 4.30 0.33 0.05 e e
0.82 1.70 1.09 1.70 1.38 1.11 0.70 3.40 0.26 0.05 0.42 0.04
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C. Fabbri et al. / Physica Medica 30 (2014) 346e351
Table 6 wTHT and EDPET assessed by ICRP60 [1] and ICRP103 [2]. SwTHT SwTHT EDPET [mSv/MBq 102] [mSv/MBq 102] [mSv/MBq 102]
ICRP60 ICRP103 ICRP60 vs ICRP103
Organs
Remainder of body
1.42 1.27 þ12%
0.36 0.46 22%
1.78 1.73 þ3%
Based on our standard clinical protocol, 18F-fluorocholine PET/ CT imaging was acquired at 50 min p.i. Moreover, 18F-fluorocholine PET/CT scans of 18 patients were performed also at 5 min p.i. to evaluate the uptake kinetics in kidneys, spleen and liver (Fig. 1). The uptake variation coefficient, CV ¼ SDSUV/meanSUV, for the organs with higher uptake (kidney, liver, pancreas, spleen) compared with the mean activity distribution in the body did not exceed 30%. In our patient population, the SUVmax values were 20e 25% higher than the SUVmean values for large organs such as the liver. A recent study by Giussani et al. [16] focused on a new compartmental model for biokinetics and dosimetry of 18F-fluorocholine in 10 prostate cancer patients. They reported the maximum values of percentage of injected activity (IA%) for liver (11%), kidneys (5%) and spleen (1%), obtained by imaging immediately after administration of radiotracer. They also pointed out that there was essentially no biological clearance in liver and spleen and therefore the clearance was by physical decay only, while urinary excretion was rapid and most of the bloodeborne activity was eliminated in the first hour p.i. Our IA% values were similar to those of Giussani [16] for the kidneys (5%) and spleen (1%), whereas a higher value was found for the liver (25%). Moreover, ã(rS, TD) and HT values (Tables 2 and 4) showed non-negligible differences with respect to those reported by Giussani [16], probably because we only considered the physical half-time of the radioisotope. Values of ã(rS, TD) for the kidneys, liver and spleen in our patients sample were also compared with those reported by Janzen’s study [14]; good agreement was observed, especially for the kidneys and spleen. However, large variability was evident among the other studies we have considered [9,10,14e17]. Furthermore, the ã(rS, TD) value was calculated by the trapezoidal rule and by assuming tb ¼ N in a group of 18 patients (Table 3). The differences with and without the 5-min time point data were 2% for kidneys and spleen and within 3% for liver; these results support our assumption of tb ¼ N relative to the calculation
Figure 2. CTDIv recorded from the PET/CT console vs patient mass (kg). The dashed line shows the median value of the CTDIv.
Table 7 Mean equivalent dose, HT, delivered to the highest exposed organs by18F-fluorocholine PET/CT scan. Organs
HT
Kidneys Liver Pancreas Salivary glands Spleen
PET
(300 MBq) mSv 29.0 25.5 18.9 12.0 12.2
HT
CT,
mSv
7.2 6.8 6.5 2.6 6.6
HT
PETþCT,
mSv
36.2 32.3 25.4 14.6 18.8
of the ã(rS, TD). The SUVbw data of the images showed that the spleen and kidneys maximum uptake values occurred within 5 min p.i., while nearly equal activity concentrations were present at 5 and 50 min p.i. in the liver. The comparison between the ED values based on ICRP Publication 60 and ICRP Publication 103 (Table 6) showed a percentage difference of less than 2% (EDPETICRP60 ¼ 1.78 mSv/100 MBq and EDPETICRP103 ¼ 1.73 mSv/100 MBq). Concerning the remainder-ofbody and organ contributions, the percent differences were 22% and þ12%, respectively. Our estimation of EDPET was very comparable with that published by Giussani [16] and Nosske and Brix [17], who reported values of 0.018 and 0.017 mSv/MBq, respectively (assuming bladder voiding every hour). Conflict of interest The authors declare that they have no conflict of interest. Acknowledgements We thank Gráine Tierney and Valia della Valle for the editorial revision of the manuscript. References [1] ICRP. The 2007 Recommendations of the International Commission on Radiological Protection. ICRP Publication 103 Ann ICRP 2007;37(2e4). [2] ICRP. 1990 Recommendations of the International Commission on Radiological Protection. ICRP Publication 60 Ann ICRP 1991;21(1e3). [3] ICRP. Adult reference computational phantoms. ICRP Publication 110 Ann ICRP 2009;39(2). [4] Erberline U, Bröer JH, Vandervoorde C, Santos P, Bardies M, Bacher K, et al. Biokinetics and dosimetry of commonly used radiopharmaceuticals in diagnostic nuclear medicine e a review. Eur J Nucl Med Mol Imaging 2011;38: 2269e81. [5] Van der Aart J, Hallet WA, Rabiner EA, Passchier J, Comley RA. Radiation dose estimates for carbon-11 labelled PET tracers. Nucl Med Biol 2012;39:305e14. [6] Hoeschen C, Mattsson S, Cantone MC, Mikuz M, Lacasta C, Ebel G, et al. Minimising activity and dose with enhanced image quality by radiopharmaceuticals administrations. Radiat Prot Dosimetry 2010;139(1e3):250e3. [7] National Electrical Manufacturers Association. NEMA standards Publication NU2-1994: performance measurements of positron emission tomographs. Washington, DC: National Electrical Manufactures Association; 1994. [8] Bolch WE, Eckerman KF, Sgouros G, Thomas SR. MIRD Pamphlet No. 21: a generalized schema for radiopharmaceutical dosimetry-standardization of nomenclature. J Nucl Med 2009;50:477e84. [9] DeGrado TR, Reiman RE, Price DT, Wang S, Coleman RE. Pharmacokinetics and radiation dosimetry of 18F-fluorocholine. J Nucl Med 2002;43(1):92e6. [10] Uusijärvi H, Nilsson LE, Bjartell A, Mattsson S. Biokinetics of 18F-choline studied in four prostate cancer patients. Radiat Prot Dosimetry 2010;139(1e3):240e4. [11] Siegel JA, Thomas SR, Stubbs JB, Stabin MG, Hays MT, Koral KF, et al. MIRD Pamphlet No 16: techniques for quantitative radiopharmaceutical biodistribution data acquisitions and analysis for use in human radiation dose estimates. J Nucl Med 1999;40:37Se61S. [12] Zanzonico PB, Finn R, Pentlow KS, Erdi Y, Beattie B, Akhurst T, et al. PET-based radiation dosimetry in man of 18F-fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer. J Nucl Med 2004;45(11):1966e71. [13] ICRP. Basic anatomical and physiological data for use in radiological protection: reference values. ICRP Publication 89 Ann ICRP 2002;32:3e4. [14] Janzen T, Tavola F, Giussani A, Cantone MC, Uusijärvi H, Mattsson S. Compartmental model of 18F-choline. Proc SPIE Int Soc Opt Eng 2010;7626: 76261e70.
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Original paper
Radiation dosimetry of cancer patients
18
F-flurocholine PET/CT studies in prostate
Cinzia Fabbri a, *, Riccardo Galassi c, Andrea Moretti c, Emanuele Sintuzzi b, Valentina Mautone b, Graziella Sarti d, Lidia Strigari e, Marcello Benassi a, Federica Matteucci b a
Medical Physics Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, FC, Italy Nuclear Medicine Unit, IRCCS IRST, Meldola, FC, Italy Nuclear Medicine Unit, Pierantoni-Morgagni Hospital, Forlì, FC, Italy d Medical Physics Unit, Bufalini Hospital, Cesena, FC, Italy e Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, IFO, Rome, Italy b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 22 April 2013 Received in revised form 20 October 2013 Accepted 25 October 2013 Available online 13 November 2013
Purpose: We aimed to evaluate the Equivalent Doses (HTs) to highly exposed organs as well as the Effective Dose (ED) for 18F-fluorocholine PET/CT scan in the follow-up of prostate cancer patients. Methods: Fifty patients were administered with 18F-fluorocholine. The activities in organs with the highest uptake were derived by region-of-interest (ROI) analysis. OLINDA/EXM1.0 and Impact software were used to assess ED for the administered 18F-fluorocholine and CT scan, respectively, and the 18Ffluorocholine and CT-scan EDs summed to yield the total ED for the PET/CT procedure. Results: The calculated 18F-fluorocholine and CT scans EDs based on ICRP Publication 103 were 5.2 mSv/ 300 MBq and 6.7 mSv, respectively. The 18F-fluorocholine HTs to the liver, kidneys, spleen and pancreas were about threefold higher than those from the CT, which contributed a greater proportion of the total ED than the 18F-fluorocholine did. Conclusions: For 18F-fluorocholine PET/CT procedures, about 40% of the ED is contributed by administered 18F-fluorocholine and 60% by the CT scan. The kidneys and liver were the highly exposed organs. Considering the large number of diagnostic procedures oncology patients undergo, radiation dosimetry is important in relation to the stochastic risk of such procedures. Ó 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
Keywords: 18 F-Fluorocholine PET/CT imaging Dosimetry Effective dose Equivalent dose Biodistribution
Introduction Administration of radiotracers to human subjects exposes them to a stochastic risk that needs to be carefully evaluated. The International Commission on Radiological Protection (ICRP) Recommendations take into account the detriment from the exposure of different organs to low doses of radiation through tissue weighting factors (wTs) that represent the relative contributions of individual organs and tissues to total detriment. The ICRP103 Recommendations [1] replaced the weighting factors published in ICRP60 [2] with substantially modified values and introduced the official computational models representing the adult Reference Male and
* Corresponding author. Medical Physics Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, FC, Italy. Tel.: þ39 3394899467. E-mail address: [email protected] (C. Fabbri).
Reference Female used in establishing radiation protection guidance [3]. Research protocols involving the clinical use of new radiotracers, such as 18F-fluorocholine, should include estimation of normal organ absorbed doses (particularly for high-uptake organs) and of the ED. In Europe, although there is no dose limit for research purposes, the ED must be evaluated and justified with respect to the calculated risk for the patient. On the other hand, the USA Food and Drug Administration for certain types of clinical research studies places limits per organ per study (generally 50 mSv, with the exception of red marrow, gonads and lens of the eye, for which 30 mSv are recommended). Moreover, while hybrid imaging techniques such as SPECT/CT and PET/CT scans allow a better diagnostic evaluation based on functional and morphological information, they deliver an ED to the patient due to internal energy deposition from radiopharmaceutical administration and external irradiation from CT X-rays. In order to optimally balance the
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C. Fabbri et al. / Physica Medica 30 (2014) 346e351
stochastic risk of diagnostic procedures [4e6] with the medical information being sought, it is important to optimize such procedures in terms of the CT parameters as well as the administered activity of the radiopharmaceutical. It should be noted that the ED is defined by ICRP for a generic reference individual and in practice it cannot actually be evaluated for individual patients. Our work contributes dosimetric data for 18F-fluorocholine used for the detection of local and distant recurrence of prostate cancer and focuses on the absorbed dose to normal organs with higher uptakes. Materials and methods
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wherein, a very fast distribution of the radiotracer was reported in organs and lesions (by 10 min p.i.), confirming the imaging acquisition at 50 min as representative of the near-steady state distribution of the radiotracer.
~ðrS ; TD Þ ¼ 1:44*t1=2p * a
OrganðrS Þtotal activity Injected activity
(1)
where rs ¼ source organ t1/2p ¼ physical half time TD ¼ N
Patients The 18F-fluorocholine PET/CT studies were approved by the local Ethics Committee and activated in our institute in October 2011. To date about 200 patients with prostate cancer have been enrolled in the study, of whom 50 were included in the dosimetric evaluations. Patients had previously undergone prostatectomy or radiotherapy with curative intent and a 18F-fluorocholine PET/CT scan was scheduled to screen for local and distant recurrence after an increase in prostate specific antigen (PSA > 1 ng/ml). Patients were injected with about 4 MBq/kg of 18F-fluorocholine (Advanced Accelerator Applications S.A., Saint Genis Pouilly, France). Imaging: acquisition, reconstruction and elaboration Imaging was performed in 2D-mode using a Discovery LS PET/ CT scanner (General Electric Medical System, Milwaukee, WI), with well-counter calibration updated every three months. The fullwidth at half maximum (FWHM) spatial resolution was 5 mm in each direction and 2D-mode sensitivity was 7.1 cps/Bq/cc, determined according to NEMA NU 2-1994 [7]. The volumetric computed tomography dose index (CTDIv) of the clinical protocol visible on the screen of the CT console was compared with the measured CTDIv by specific phantom tests; the agreement was good, with a percentage difference of less than 4%. Whole-body PET images were acquired 50 min post-injection (p.i.) from the nose to the mid-thigh (6e7 bed positions, 3e3.5 min/ bed). CT acquisition parameters were as follows: 120 kV, 90 mA, 0.75e1.5 pitch, 0.8 s/rot, 20 mm collimation, 5 mm slice thickness. PET data were corrected for scatter, randoms, dead time and decay and images were reconstructed using a 2D Ordered-SubsetsExpectation Maximization (OSEM) iterative reconstruction algorithm (2 iterations, 28 subsets). Image analysis was carried out using Xeleris1 GE software. In particular, ROIs of 2 cm in diameter were drawn within each source organ on three/four slices selected at the top, in the middle and at the bottom of the organ and the mean value of the Standard Uptake Value calculated with body weight (SUVbw) on the three/four slices of each organ was calculated. The source regions were bone, fat, kidneys, liver, lungs, muscle, pancreas, salivary glands (parotids and submandibular glands), spleen, small intestine and testes. Moreover, in a group of 18 patients we performed also an early acquisition (within 5 min p.i.) in order to evaluate the uptake kinetics in the highly exposed organs (kidneys, liver and spleen). Biodistribution and dosimetric study The mean activity concentration (kBq/ml) and the percentage of injected activity (%IA) for all 50 patients were obtained for each organ at 50 min p.i. The time integrated-activity coefficients [8], ã(rS, TD), were calculated assuming no biologic removal, tb ¼ N (equation (1)) according to data from a number of studies [9,10]
Furthermore, for the 18 patients with acquisitions at 5 and 50 min p.i. the time integrated-activity coefficients were calculated in kidneys, spleen and liver by applying the trapezoidal rule [11] and with physical decay only assumed for integration from 50 min on. The above values were compared in term of percentage difference with those obtained by assuming no biological removal. The calculation of the total organ activity was determined taking into account the organ reference masses and the standard-man total body mass of the reference male and the standard uptake value [12]. We used OLINDA/EXM1.0 software to calculate the equivalent doses, HTs (mSv/MBq), entering the ã(rS, TD) of each source organ (liver, lungs, kidneys, muscle, pancreas, small intestine, spleen, testes, red marrow, urinary content and remainder-of-body) and using the sphere model to obtain the HT for salivary glands. The mass of the parotid glands was assumed equal to 50 g and the mass of the submandibular glands 25 g [13]. The ã(rS, TD) of blood and urinary bladder contents reported in the literature [14,15] was used to calculate the HT for red marrow and urinary bladder wall, respectively, since it was not possible to collect and count samples of blood and urine. A bladder voiding interval of 1 h was assumed [14,15] and because of the absence of specific uptake in the bones and red marrow, red marrow time integrated-activity coefficient was calculated by the blood-based method (which assumes a linear relation between the blood and red marrow time integratedactivity coefficient). The proportionality factor was the ratio between standard-man red marrow mass and standard-man blood mass. ED (mSv/MBq) was calculated by summing the products of the organ equivalent doses HTs and their respective organ weighting factors and adding the remainder-of-body ED contribution according to the different calculation algorithms and wTs proposed in ICRP60 [2] and ICRP103 Recommendations [1]. In particular, to determine the remainder-of-body ED contribution as stated in ICRP103, the remainder tissues mean HT was multiplied for the relative wT equal to 0.12 [2]. Instead, to obtain the remainder-ofbody ED contribution according to the ICRP Publication 60, in those exceptional cases in which one single organ of the remainder (in our specific case the kidney) receives an equivalent dose in excess of the highest dose in any of the twelve organs (or tissues) for which a wT is specified [1], a weighting factor of 0.025 was applied to that organ (kidney) and a weighting factor of 0.025 to the average dose calculated among the other organs of the remainder. The comparison was performed in order to evaluate possible significant differences, in terms of percentage differences, calculated as showed in equation (2), between the ED values based on ICRP Recommendations 103 and 60 [1,2].
%DIFFðEDICRP60 vs EDICRP103 Þ ¼
EDICRP60 EDICRP103 *100 EDICRP103
(2)
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Figure 1. 18F-Fluorocholine PET/CT of patient submitted to prostatectomy, 71 years old, 100 kg, PSA 1.92 ng/ml, injected with 253 MBq. A) 5 min p.i., B) 50 min p.i. Although both images show pathological uptake in skeletal and lymph node sites, the early image has higher background activity.
The ED-based on ICRP103 tissue weighting factors was calculated using an EXCEL algorithm, since only ICRP60 weighting factors are used in OLINDA/EXM1.0 software for the calculation of the ED. In addition, the ED of the CT scan was evaluated by inserting the acquisition parameters of a standard examination into Impact software (www.impactscan.org), which gave us the opportunity of analyzing data taking into consideration both ICRP60 and ICRP103 weighting factors. Table 1 SUVbw mean values of organs obtained from 18F-fluorocholine PET/CT images of 50 patients acquired 50 min p.i. Organs
SUVbw SD
Bladder Bone (healthy femur) Subcutaneous fat Kidney parenchyma Liver Lungs Skeletal muscle (gluteus muscle) Pancreas Parotid glands Small intestine Spleen Submandibular glands Testes
15.9 18.5 0.8 0.6 0.3 0.2 13.1 3.6 9.7 2.5 1.0 0.3 1.0 0.4 8.1 2.1 6.4 1.9 2.1 0.9 4.7 0.9 6.9 2.1 0.9 0.3
Results Effective dose from PET scan The mean age of this group of patients was 71 years (range 45e 92) and mean weight was 84 kg (range 58e110). The mean activity injected was 3.3 MBq/kg (range 1.8e4.4). Figure 1 shows two images acquired A) 5 min and B) 50 min p.i. (253 MBq) of a 71-year-old patient who had previously undergone prostatectomy. PSA was 1.92 ng/ml and weight was 100 kg. CTDIv was equal to 7.5 mSv with120 kV and 140 mA as acquisition parameters. Both images demonstrated 18F-fluorocholine pathological uptake in skeletal and lymph node sites, although in the early image (A) a greater background activity and a higher activity concentration in the urinary system were evident. Table 1 shows the mean values and standard deviation (SD) of the SUVbw of the 50 patients at 50 min p.i.; the highest values were found in the bladder, kidneys, liver, pancreas, salivary glands and spleen. Table 2 shows the time-integrated activity coefficients ã(rS, TD) for the source organs relative to IRST patients (column 2) with respect to those reported by Giussani for the Reference Patient (column 3) [16], Janzen (column 4) [14,15], Nosske and Brix (column 5) [17] and DeGrado (column 6) [9]. Table 3 reports the ã(rS, TD) calculated by the trapezoidal rule (column 2) and by assuming no biological removal (column 3) in 18
C. Fabbri et al. / Physica Medica 30 (2014) 346e351 Table 2 Time-integrated activity coefficients ã(rS, TD) (h) (no biological removal, tb ¼ N) relative to IRST pts (column 2) compared with those presented for the reference patient by Giussani [16] (column 3), Janzen [14,15] (column 4), Nosske and Brix [17] (column 5) and DeGrado [9,19] (column 6). Organ
IRST 2012
Giussani Janzen Nosske and DeGrado 2012 2011 Brix 2009 2002
Liver 0.652 0.140 Spleen 0.031 0.006 Pancreas 0.027 0.007 Kidneys 0.142 0.039 Small intestine 0.047 0.019 Lungs 0.038 0.014 Testes 0.0013 0.0006 Parotid glands 0.011 0.0035 Submandibular 0.0064 0.0018 glands Muscle 0.984 0.377 Urinary bladder e contents Blood Remainder-of-body 0.576 a b c
0.422 0.022 e 0.114 e e e e e
0.410 0.024 e 0.120 e e e e e
0.37 0.053 e 0.24 e e e e e
0.142 0.0297 e 0.219 e e e e e
e 0.039a 0.119b 0.270 1.621
e 0.043a
e 0.078b
e 0.048c
0.344 1.569
1.87 e
Bladder voiding interval, 1 h. Bladder voiding interval, 3.5 h. Dynamic bladder voiding was not used.
patients with acquisitions at 5 and 50 min p.i. The percentage difference (%DIFF ¼ (ã(rS, TD)trap ã(rS, TD)tb¼N)/ã(rS, TD)tb¼N) was within 2% for kidneys and spleen and 3% for liver. Table 4 shows the mean values of HT for our patients (column 2) together with the HT values published by Giussani for a Reference Patient (column 3) [16], Janzen (column 4) [14,15], Nosske and Brix (column 5) [17] and DeGrado (column 6) [9,19]. Table 5 shows the wT for organs and their contribution (wT*HT) to the EDPET. As not all target organs were included in our evaluation, the sum of wT was 0.95 for ICRP103 and 0.94 for ICRP60 [18]. Therefore, we multiplied the mean value of equivalent dose, HT, relative to the total body and provided by OLINDA/EXM1.0 software (Table 4), by the wT of the organs not included in our analysis in order to obtain the final estimate of EDPET. The total contribution of the organs listed in Table 6 to the EDPET was 14.2 mSv/MBq and 12.7 mSv/MBq calculated by ICRP60 and ICRP103, respectively, while the contribution of the remainder of body was 3.6 mSv/MBq (ICRP60) and 4.6 mSv/MBq (ICRP103), respectively. The highest percentage differences (ICRP60 vs ICRP103) were 22% for the contribution of the Remainder of body to the EDPET and þ12% for the contribution of the organs (Table 6). Finally, the impact on the total EDPET of the different wTs was about þ3%. It is noteworthy that the liver was the organ that contributed the highest percentage (24%) to the EDPET. Effective dose from CT scan Figure 2 shows the distribution of the CTDIv (mSv) values vs patient mass (kg). The dashed line is the median CTDIv value (5.4 mSv). The mean value of CTDIv was 6.3 mSv (range 3.2e15 mSv). Table 3 Time-integrated activity coefficients ã(rS, TD) (h) relative to kidneys, spleen and liver in a group of 18 patients calculated by the trapezoidal rule (column 2) and by assuming no biological removal (tb ¼ N) (column 3). Organ
kidneys Spleen Liver
Time-integrated activity coefficients ã(rS, TD), (h)
Time-integrated activity coefficients ã(rS, TD), (h)
Trapezoidal rule
No biological removal (tb ¼ N)
0.175 0.056 0.035 0.008 0.602 0.175
0.171 0.055 0.035 0.009 0.620 0.184
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Table 4 Mean values of equivalent doses, HTs, calculated for our cohort of 50 patients (column 2) compared to the reference patient from Giussani (column 3) [16], Janzen (column 4) [14,15], Nosske and Brix (column 5) [17] and DeGrado (column 6) [9,19]. HT [mSv/MBq 102] Organs
IRST
Giussani
Janzen
NosskeeBrix
DeGrado
Liver Spleen Pancreas Kidneys Small intestine Lungs Testes Muscle Urinary bladder wall Adrenal glands Brain Breast Gallbladder wall Colon wall Stomach wall ULI wall Heart wall Osteogenic cells Skin Thymus Thyroid Red marrow Salivary glands Total body
8.49 4.07 6.29 9.66 1.92 1.42 1.02 1.18 2.77 1.76 0.42 0.58 2.27 0.91 1.15 1.23 1.07 1.23 0.52 0.74 0.65 1.42 4.2 1.25
5.6 3.0 1.6 7.8 1.3 1.1 0.93 1.0 2.9 1.7 0.82 0.85 e 1.3 1.3 e e e 0.78 1.0 0.95 1.0 e
6.2 4.2 e 8.3 e e e e 1.7 e e e e e e e e e e e e e e e
5.1 6.3 e 15 e e e e 4.7 e e e e e e e e e e e e e e e
5.16 4.73 e 14.8 2.1 1.03 1.05 1.0 3.32 e e e e e e e e e e e 1.32 1.54 e e
It must be pointed out that the highest values belong to the first enrolled patients when CT acquisition parameters, in particular mA, were set at a higher level. Subsequently, as the most frequent site of recurrence is the bone or lymph nodes, the physicians decided that it was feasible to accept a slight reduction in the quality of images, resulting in dose-sparing for patients. The ED of the CT scan was 6.8 mSv and 6.7 mSv based on ICRP60 and ICRP103 wTs, respectively. Table 7 shows the mean values of HT PET, HT CT and their sum (HT 18 F-fluoPETþCT) for the organs showing the highest uptake of rocholine. Interestingly, the dose equivalent values for the kidneys, liver and pancreas from the PET scan were about threefold higher than those from the CT scan. Discussion and conclusion The present study investigated the organ equivalent doses, HTs and the effective dose, ED, based on a ROI analysis of images obtained in a large cohort of patients who underwent 18F-fluorocholine PET/CT diagnostic procedures to screen for local and distance recurrence after increase of PSA. Table 5 wT*HT of the organs calculated by applying wT from ICRP60 [1] and ICRP103 [2]. Organs Testes Red bone marrow Colon Lungs Stomach Bladder Breast Liver Thyroid Skin Salivary glands Brain
wT ICRP60
wT ICRP103
wT*HT ICRP60 [mSv/MBq]
wT*HT ICRP103 [mSv/MBq]
0.20 0.12 0.12 0.12 0.12 0.05 0.05 0.05 0.05 0.01 e e
0.08 0.12 0.12 0.12 0.12 0.04 0.12 0.04 0.04 0.01 0.01 0.01
2.04 1.70 1.09 1.70 1.38 1.39 0.29 4.30 0.33 0.05 e e
0.82 1.70 1.09 1.70 1.38 1.11 0.70 3.40 0.26 0.05 0.42 0.04
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Table 6 wTHT and EDPET assessed by ICRP60 [1] and ICRP103 [2]. SwTHT SwTHT EDPET [mSv/MBq 102] [mSv/MBq 102] [mSv/MBq 102]
ICRP60 ICRP103 ICRP60 vs ICRP103
Organs
Remainder of body
1.42 1.27 þ12%
0.36 0.46 22%
1.78 1.73 þ3%
Based on our standard clinical protocol, 18F-fluorocholine PET/ CT imaging was acquired at 50 min p.i. Moreover, 18F-fluorocholine PET/CT scans of 18 patients were performed also at 5 min p.i. to evaluate the uptake kinetics in kidneys, spleen and liver (Fig. 1). The uptake variation coefficient, CV ¼ SDSUV/meanSUV, for the organs with higher uptake (kidney, liver, pancreas, spleen) compared with the mean activity distribution in the body did not exceed 30%. In our patient population, the SUVmax values were 20e 25% higher than the SUVmean values for large organs such as the liver. A recent study by Giussani et al. [16] focused on a new compartmental model for biokinetics and dosimetry of 18F-fluorocholine in 10 prostate cancer patients. They reported the maximum values of percentage of injected activity (IA%) for liver (11%), kidneys (5%) and spleen (1%), obtained by imaging immediately after administration of radiotracer. They also pointed out that there was essentially no biological clearance in liver and spleen and therefore the clearance was by physical decay only, while urinary excretion was rapid and most of the bloodeborne activity was eliminated in the first hour p.i. Our IA% values were similar to those of Giussani [16] for the kidneys (5%) and spleen (1%), whereas a higher value was found for the liver (25%). Moreover, ã(rS, TD) and HT values (Tables 2 and 4) showed non-negligible differences with respect to those reported by Giussani [16], probably because we only considered the physical half-time of the radioisotope. Values of ã(rS, TD) for the kidneys, liver and spleen in our patients sample were also compared with those reported by Janzen’s study [14]; good agreement was observed, especially for the kidneys and spleen. However, large variability was evident among the other studies we have considered [9,10,14e17]. Furthermore, the ã(rS, TD) value was calculated by the trapezoidal rule and by assuming tb ¼ N in a group of 18 patients (Table 3). The differences with and without the 5-min time point data were 2% for kidneys and spleen and within 3% for liver; these results support our assumption of tb ¼ N relative to the calculation
Figure 2. CTDIv recorded from the PET/CT console vs patient mass (kg). The dashed line shows the median value of the CTDIv.
Table 7 Mean equivalent dose, HT, delivered to the highest exposed organs by18F-fluorocholine PET/CT scan. Organs
HT
Kidneys Liver Pancreas Salivary glands Spleen
PET
(300 MBq) mSv 29.0 25.5 18.9 12.0 12.2
HT
CT,
mSv
7.2 6.8 6.5 2.6 6.6
HT
PETþCT,
mSv
36.2 32.3 25.4 14.6 18.8
of the ã(rS, TD). The SUVbw data of the images showed that the spleen and kidneys maximum uptake values occurred within 5 min p.i., while nearly equal activity concentrations were present at 5 and 50 min p.i. in the liver. The comparison between the ED values based on ICRP Publication 60 and ICRP Publication 103 (Table 6) showed a percentage difference of less than 2% (EDPETICRP60 ¼ 1.78 mSv/100 MBq and EDPETICRP103 ¼ 1.73 mSv/100 MBq). Concerning the remainder-ofbody and organ contributions, the percent differences were 22% and þ12%, respectively. Our estimation of EDPET was very comparable with that published by Giussani [16] and Nosske and Brix [17], who reported values of 0.018 and 0.017 mSv/MBq, respectively (assuming bladder voiding every hour). Conflict of interest The authors declare that they have no conflict of interest. Acknowledgements We thank Gráine Tierney and Valia della Valle for the editorial revision of the manuscript. References [1] ICRP. The 2007 Recommendations of the International Commission on Radiological Protection. ICRP Publication 103 Ann ICRP 2007;37(2e4). [2] ICRP. 1990 Recommendations of the International Commission on Radiological Protection. ICRP Publication 60 Ann ICRP 1991;21(1e3). [3] ICRP. Adult reference computational phantoms. ICRP Publication 110 Ann ICRP 2009;39(2). [4] Erberline U, Bröer JH, Vandervoorde C, Santos P, Bardies M, Bacher K, et al. Biokinetics and dosimetry of commonly used radiopharmaceuticals in diagnostic nuclear medicine e a review. Eur J Nucl Med Mol Imaging 2011;38: 2269e81. [5] Van der Aart J, Hallet WA, Rabiner EA, Passchier J, Comley RA. Radiation dose estimates for carbon-11 labelled PET tracers. Nucl Med Biol 2012;39:305e14. [6] Hoeschen C, Mattsson S, Cantone MC, Mikuz M, Lacasta C, Ebel G, et al. Minimising activity and dose with enhanced image quality by radiopharmaceuticals administrations. Radiat Prot Dosimetry 2010;139(1e3):250e3. [7] National Electrical Manufacturers Association. NEMA standards Publication NU2-1994: performance measurements of positron emission tomographs. Washington, DC: National Electrical Manufactures Association; 1994. [8] Bolch WE, Eckerman KF, Sgouros G, Thomas SR. MIRD Pamphlet No. 21: a generalized schema for radiopharmaceutical dosimetry-standardization of nomenclature. J Nucl Med 2009;50:477e84. [9] DeGrado TR, Reiman RE, Price DT, Wang S, Coleman RE. Pharmacokinetics and radiation dosimetry of 18F-fluorocholine. J Nucl Med 2002;43(1):92e6. [10] Uusijärvi H, Nilsson LE, Bjartell A, Mattsson S. Biokinetics of 18F-choline studied in four prostate cancer patients. Radiat Prot Dosimetry 2010;139(1e3):240e4. [11] Siegel JA, Thomas SR, Stubbs JB, Stabin MG, Hays MT, Koral KF, et al. MIRD Pamphlet No 16: techniques for quantitative radiopharmaceutical biodistribution data acquisitions and analysis for use in human radiation dose estimates. J Nucl Med 1999;40:37Se61S. [12] Zanzonico PB, Finn R, Pentlow KS, Erdi Y, Beattie B, Akhurst T, et al. PET-based radiation dosimetry in man of 18F-fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer. J Nucl Med 2004;45(11):1966e71. [13] ICRP. Basic anatomical and physiological data for use in radiological protection: reference values. ICRP Publication 89 Ann ICRP 2002;32:3e4. [14] Janzen T, Tavola F, Giussani A, Cantone MC, Uusijärvi H, Mattsson S. Compartmental model of 18F-choline. Proc SPIE Int Soc Opt Eng 2010;7626: 76261e70.
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