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Molecular imaging of advanced prostate cancer
Curr Probl Cancer 39 (2015) 29–32
Contents lists available at ScienceDirect
Curr Probl Cancer journal homepage: www.elsevier.com/locate/cpcancer
Molecular imaging of advanced prostate cancer Peter J. Rossi, MD, David M. Schuster, MD
Modern imaging tools for advanced prostate cancer Advanced prostate cancer presents a diagnostic challenge to clinicians. Although prostate cancer prevalence may be declining, it still remains the second highest cause of cancer death.1 The treatment of prostate cancer in advanced stages requires significant intervention, including surgery, chemotherapy, radiotherapy, and supportive care, and remains a major public health problem. Earlier detection and identification of advanced prostate cancer is a diagnostic dilemma. In this summary, we review the status and future direction of molecular imaging for advanced prostate cancer (Figs. 1 and 2). Clinical imaging tools employed in the diagnosis of prostate cancer include transrectal ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and bone scans. Unfortunately, the likelihood of disease detection with these modalities is low. Surgical series have shown that transrectal ultrasound may understage disease 30% of the time.2 Ultrasound is a mainstay of therapy, but the accuracy in cancer diagnosis is between 52% and 62%, suggesting limitations to universalize this technique for many clinical scenarios.3 Transrectal ultrasound may also be used when patients have failed initial therapy and other imaging has not detected disease, but similar limitations persist. MRI is commonly used at diagnosis and on recurrence. The T2 sequence is best suited for evaluating disease in the prostate, with areas of low intensity suggestive of prostate cancer vs benign tissue.4 Overall, MRI is effective in delineating soft tissue and can be an excellent technique for targeted therapy; however, the sensitivity and specificity is variable, especially in the posttherapy and postbiopsy settings. The reported data of diagnostic efficacy are dependent on the study population's methods and the sequencing and programming protocols used.5 Dynamic contrast-enhanced MRI exhibits improved sensitivity and specificity and may be helpful in delineating tumor from scar but may also be confounded by blood product remnants within the prostate.6 When evaluating for metastatic disease, a Technetium-99m bone scan is the mainstay of imaging. Published data indicate that routine whole-body bone scan underestimates disease and has low sensitivity and specificity. Choueiri et al7 reported in the scenario where prostrate-specific antigen (PSA) rises following therapy, and a bone scan, conventional CT, and MRI are used, the chance of detecting disease increases when the PSA is more than 5 ng/mL and the doubling time is http://dx.doi.org/10.1016/j.currproblcancer.2014.11.005 0147-0272/& 2014 Elsevier Inc. All rights reserved.
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P.J. Rossi, D.M. Schuster / Curr Probl Cancer 39 (2015) 29–32
Fig. 1. FACBC (upper row) and ProstaScint (lower row) studies in a 65-year-old male patient with recurrent prostate cancer, a PSA of 14 ng/mL, and imaging demonstrating a common iliac nodal recurrence. FACBC, fluorocyclobutyl-1carboxylic acid. (Color version of figure is available online.)
less than 10 months. In this setting, the concordance index for positive imaging findings increases significantly and approaches 84%. In this report, CT was less likely than bone scan or MR to find the source of recurrent disease.7 At this time, the American Urologic Association recommends routine use of bone scans in the setting of recurrence but questions its efficacy with PSA less than 10 ng/ mL and PSA doubling time greater than 6 months. The American College of Radiology Appropriateness Criteria suggest a bone scan should be used first to rule out metastatic disease in the setting of advanced prostate cancer before other imaging.8 In the setting of advanced disease, CT has low likelihood of detection of local disease, and MRI may be preferred owing to higher sensitivity and specificity. Although MRI sensitivity ranges from 48% to 61% and specificity from 52% to 82%, it remains the most accurate available imaging modality.9 111 In-capromab pendetide (ProstaScint) scan has been proposed as a more accurate imaging modality in these situations. Hinkle et al10 suggested a sensitivity of 75% and specificity of 86% in
Fig. 2. FACBC study in a man with a PSA rise after radiotherapy. CT and MRI showed negative findings. FACBC detected 7-mm aortocaval lymph node (shown), which showed malignancy on laparoscopic biopsy. FACBC, fluorocyclobutyl1-carboxylic acid. (Color version of figure is available online.)
P.J. Rossi, D.M. Schuster / Curr Probl Cancer 39 (2015) 29–32
31
the detection of patients with prostate carcinoma who are at high risk for metastatic disease; however, subsequent publications have revealed wide variance in efficacy of disease detection. Schuster et al11 reported a sensitivity of 67% for disease detection in the prostate bed but a sensitivity of only 10% for extraprostatic disease detection. 18F-fluorodeoxyglucose (FDG)positron emission tomography (PET)/CT has also been studied in advanced prostate cancer, but sensitivity and specificity rates are disappointing, ranging between 31% and 61%. 18F-FDG-PET, although promising, has the limitation of intense bladder activity that can obscure the prostate bed.12 Owing to the limitations of the common imaging modalities we use in this situation of recurrent or advanced prostate cancer, other modalities have been proposed and are the subjects of ongoing clinical study. 18 F-sodium fluoride (18F-NaF) PET has increasing utility in clinical practice for detection of osseous disease in advanced prostate cancer. This radiotracer was Food and Drug Administration (FDA) approved for use in 1972. The radiotracer mechanism of action is chemisorption with exchange of 18F ion for OH ion to form fluorapatite and then migration into crystal matrix of bone. The tracer also is rapidly cleared. In a review by Even-Sapir et al13 in 2006, NaF showed better sensitivity and specificity, both at 100%, than routine bone scan. The sensitivity and specificity for routine bone scan was 82% and 57%. The authors view this study as a useful tool at this time. There are a number of molecular imaging tools receiving attention at this time, namely 11 C-choline and 11C-acetate PET/CT, 18F-fluorocholine PET/CT, 18F-fluorocyclobutyl-1-carboxylic acid (FACBC) PET/CT, and new prostate-specific membrane antigen (PSMA)–targeting radiotracers. 11C-acetate PET/CT takes advantage of fatty acid synthase upregulation in prostate cancer14 and has little urinary excretion. Mena et al15 reported that the sensitivity and specificity is approximately 62% and 80%, respectively, and shows greatest benefit for detection of recurrence in advanced prostate cancer. In another study by Oyama et al,16 the reported detection rate is 59% with PSA4 3 ng/mL and 4% with o 3 ng/mL. Similarly, the choline radiotracers exploit the overexpression of choline kinase from cell proliferation in prostate cancer. Detection rate for recurrent disease is dependent on PSA level, and although a 44.1% positivity rate has been reported with PSA o1 ng/mL, detection rate increases to 88.5% with PSA 4 5 ng/mL.17 Currently these PET radiotracers are primarily used in the setting of recurrent disease and are under clinical trial at multiple institutions. 11C-choline is now FDA approved in limited settings, but the choline radiotracers are widely used outside of the United States. Another molecular imaging radiotracer 18F-FACBC is transported similar to glutamine, which is an important substrate for tumor metabolism. Schuster et al18 have reported on imaging of 115 patients with suspected recurrent prostate cancer, with a whole-body detection rate of 81.7%, though detection rate is also dependent on PSA level, with 39% detection with PSA between 0 and 1 ng/mL and greater than 90% with a PSA 4 2 ng/mL. Nanni et al19 studied 28 men with biochemical failure after prostatectomy where the mean PSA was 2.9 ng/mL. 11C-choline was compared with FACBC. In 5 patients, the 11C-choline was positive compared with 10 patients with the FACBC study, with better lesion conspicuity on FACBC PET. Turkbey et al reported that the addition of FACBC to MR increased the positive predictive value for detection of recurrent disease from 75% to 82%, suggesting that there may be utility in combining these imaging tools.20 Current clinical investigation includes prospective studies evaluating the role and effect on clinical decision of FACBC in the setting of recurrence after surgery, radiotherapy, and cryotherapy. Finally, new PSMA-targeting radiotracers such as 18F-N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-[18F]fluorobenzyl-L-cysteine, which targets the extracellular domain responsible for enzymatic activity,21 and 68Ga-PSMA22 are showing improved performance compared with 111 In-capromab pendetide and may represent a promising alternative to conventional imaging in the future. In conclusion, the detection of advanced prostate cancer remains a significant clinical challenge. Currently ultrasound, MRI, CT, and bone scans are mainstays of our diagnostic tools. 18F-NaF PET/CT is available today and FDA approved and has substantial data supporting its usage. Molecular imaging techniques, namely, 11C-choline and 11C-acetate PET/CT,
32
P.J. Rossi, D.M. Schuster / Curr Probl Cancer 39 (2015) 29–32
18 F-fluorocholine PET/CT, 18F-FACBC PET/CT, and new PSMA-targeting radiotracers, have shown promise and are an area of intense investigation at this time.
References 1. DeSantis CE, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin 2014;64(4):252–271. 2. Freedland SJ, et al. Upgrading and downgrading of prostate needle biopsy specimens: risk factors and clinical implications. Urology 2007;69(3):495–499. 3. Heijmink SW, et al. State-of-the-art uroradiologic imaging in the diagnosis of prostate cancer. Acta Oncol 2011; 50(suppl 1):25–38. 4. Turkbey B, et al. Imaging localized prostate cancer: current approaches and new developments. Am J Roentgenol 2009;192(6):1471–1480. 5. Murphy G, et al. The expanding role of MRI in prostate cancer. Am J Roentgenol 2013;201(6):1229–1238. 6. Turkbey B, Pinto PA, Choyke PL. Imaging techniques for prostate cancer: implications for focal therapy. Nat Rev Urol 2009;6(4):191–203. 7. Choueiri TK, et al. A model that predicts the probability of positive imaging in prostate cancer cases with biochemical failure after initial definitive local therapy. J Urol 2008;179(3):906–910. [discussion 910]. 8. Eberhardt SC, et al. ACR Appropriateness Criteria prostate cancer—pretreatment detection, staging, and surveillance. J Am Coll Radiol 2013;10(2):83–92. 9. Casalino DD, et al. ACR Appropriateness Criteria(R) posttreatment follow-up of prostate cancer. J Am Coll Radiol 2011;8(12):863–871. 10. Hinkle GH, et al. Multicenter radioimmunoscintigraphic evaluation of patients with prostate carcinoma using indium-111 capromab pendetide. Cancer 1998;83(4):739–747. 11. Schuster DM, et al. Characterization of primary prostate carcinoma by anti-1-amino-2-[(18)F] -fluorocyclobutane-1carboxylic acid (anti-3-[(18)F] FACBC) uptake. Am J Nucl Med Mol Imaging 2013;3(1):85–96. 12. Pfluger T, et al. Diagnostic value of combined 18F-FDG PET/MRI for staging and restaging in paediatric oncology. Eur J Nucl Med Mol Imaging 2012;39(11):1745–1755. 13. Even-Sapir E, et al. The detection of bone metastases in patients with high-risk prostate cancer: 99mTc-MDP Planar bone scintigraphy, single- and multi-field-of-view SPECT, 18F-fluoride PET, and 18F-fluoride PET/CT. J Nucl Med 2006;47(2):287–297. 14. Pfluger T, et al. Integrated imaging using MRI and 123I metaiodobenzylguanidine scintigraphy to improve sensitivity and specificity in the diagnosis of pediatric neuroblastoma. Am J Roentgenol 2003;181(4):1115–1124. 15. Mena E, et al. 11C-Acetate PET/CT in localized prostate cancer: a study with MRI and histopathologic correlation. J Nucl Med 2012;53(4):538–545. 16. Oyama N, et al. 11C-acetate PET imaging of prostate cancer: detection of recurrent disease at PSA relapse. J Nucl Med 2003;44(4):549–555. 17. Mitchell CR, et al. Operational characteristics of (11)C-choline positron emission tomography/computerized tomography for prostate cancer with biochemical recurrence after initial treatment. J Urol 2013;189(4):1308–1313. 18. Schuster DM, et al. Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography and (111)Incapromab pendetide single photon emission computerized tomography-computerized tomography for recurrent prostate carcinoma: results of a prospective clinical trial. J Urol 2014;191(5):1446–1453. 19. Nanni C, et al. 18F-FACBC compared with 11C-choline PET/CT in patients with biochemical relapse after radical prostatectomy: a prospective study in 28 patients. Clin Genitourin Cancer 2014;12(2):106–110. 20. Turkbey B, Mena E, Shih J, et al. Localized prostate cancer detection with 18F FACBC PET/CT: comparison with MR imaging and histopathologic analysis. Radiology 2014;270(3):849–856. doi: 10.1148/radiol.13130240. Epub 2013 Nov 8. 21. Cho SY, Gage KL, Mease RC, et al. Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a lowmolecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer. J Nucl Med 2012;53:1883. 22. Afshar-Oromieh A, et al. Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2013;40:486.
Contents lists available at ScienceDirect
Curr Probl Cancer journal homepage: www.elsevier.com/locate/cpcancer
Molecular imaging of advanced prostate cancer Peter J. Rossi, MD, David M. Schuster, MD
Modern imaging tools for advanced prostate cancer Advanced prostate cancer presents a diagnostic challenge to clinicians. Although prostate cancer prevalence may be declining, it still remains the second highest cause of cancer death.1 The treatment of prostate cancer in advanced stages requires significant intervention, including surgery, chemotherapy, radiotherapy, and supportive care, and remains a major public health problem. Earlier detection and identification of advanced prostate cancer is a diagnostic dilemma. In this summary, we review the status and future direction of molecular imaging for advanced prostate cancer (Figs. 1 and 2). Clinical imaging tools employed in the diagnosis of prostate cancer include transrectal ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and bone scans. Unfortunately, the likelihood of disease detection with these modalities is low. Surgical series have shown that transrectal ultrasound may understage disease 30% of the time.2 Ultrasound is a mainstay of therapy, but the accuracy in cancer diagnosis is between 52% and 62%, suggesting limitations to universalize this technique for many clinical scenarios.3 Transrectal ultrasound may also be used when patients have failed initial therapy and other imaging has not detected disease, but similar limitations persist. MRI is commonly used at diagnosis and on recurrence. The T2 sequence is best suited for evaluating disease in the prostate, with areas of low intensity suggestive of prostate cancer vs benign tissue.4 Overall, MRI is effective in delineating soft tissue and can be an excellent technique for targeted therapy; however, the sensitivity and specificity is variable, especially in the posttherapy and postbiopsy settings. The reported data of diagnostic efficacy are dependent on the study population's methods and the sequencing and programming protocols used.5 Dynamic contrast-enhanced MRI exhibits improved sensitivity and specificity and may be helpful in delineating tumor from scar but may also be confounded by blood product remnants within the prostate.6 When evaluating for metastatic disease, a Technetium-99m bone scan is the mainstay of imaging. Published data indicate that routine whole-body bone scan underestimates disease and has low sensitivity and specificity. Choueiri et al7 reported in the scenario where prostrate-specific antigen (PSA) rises following therapy, and a bone scan, conventional CT, and MRI are used, the chance of detecting disease increases when the PSA is more than 5 ng/mL and the doubling time is http://dx.doi.org/10.1016/j.currproblcancer.2014.11.005 0147-0272/& 2014 Elsevier Inc. All rights reserved.
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P.J. Rossi, D.M. Schuster / Curr Probl Cancer 39 (2015) 29–32
Fig. 1. FACBC (upper row) and ProstaScint (lower row) studies in a 65-year-old male patient with recurrent prostate cancer, a PSA of 14 ng/mL, and imaging demonstrating a common iliac nodal recurrence. FACBC, fluorocyclobutyl-1carboxylic acid. (Color version of figure is available online.)
less than 10 months. In this setting, the concordance index for positive imaging findings increases significantly and approaches 84%. In this report, CT was less likely than bone scan or MR to find the source of recurrent disease.7 At this time, the American Urologic Association recommends routine use of bone scans in the setting of recurrence but questions its efficacy with PSA less than 10 ng/ mL and PSA doubling time greater than 6 months. The American College of Radiology Appropriateness Criteria suggest a bone scan should be used first to rule out metastatic disease in the setting of advanced prostate cancer before other imaging.8 In the setting of advanced disease, CT has low likelihood of detection of local disease, and MRI may be preferred owing to higher sensitivity and specificity. Although MRI sensitivity ranges from 48% to 61% and specificity from 52% to 82%, it remains the most accurate available imaging modality.9 111 In-capromab pendetide (ProstaScint) scan has been proposed as a more accurate imaging modality in these situations. Hinkle et al10 suggested a sensitivity of 75% and specificity of 86% in
Fig. 2. FACBC study in a man with a PSA rise after radiotherapy. CT and MRI showed negative findings. FACBC detected 7-mm aortocaval lymph node (shown), which showed malignancy on laparoscopic biopsy. FACBC, fluorocyclobutyl1-carboxylic acid. (Color version of figure is available online.)
P.J. Rossi, D.M. Schuster / Curr Probl Cancer 39 (2015) 29–32
31
the detection of patients with prostate carcinoma who are at high risk for metastatic disease; however, subsequent publications have revealed wide variance in efficacy of disease detection. Schuster et al11 reported a sensitivity of 67% for disease detection in the prostate bed but a sensitivity of only 10% for extraprostatic disease detection. 18F-fluorodeoxyglucose (FDG)positron emission tomography (PET)/CT has also been studied in advanced prostate cancer, but sensitivity and specificity rates are disappointing, ranging between 31% and 61%. 18F-FDG-PET, although promising, has the limitation of intense bladder activity that can obscure the prostate bed.12 Owing to the limitations of the common imaging modalities we use in this situation of recurrent or advanced prostate cancer, other modalities have been proposed and are the subjects of ongoing clinical study. 18 F-sodium fluoride (18F-NaF) PET has increasing utility in clinical practice for detection of osseous disease in advanced prostate cancer. This radiotracer was Food and Drug Administration (FDA) approved for use in 1972. The radiotracer mechanism of action is chemisorption with exchange of 18F ion for OH ion to form fluorapatite and then migration into crystal matrix of bone. The tracer also is rapidly cleared. In a review by Even-Sapir et al13 in 2006, NaF showed better sensitivity and specificity, both at 100%, than routine bone scan. The sensitivity and specificity for routine bone scan was 82% and 57%. The authors view this study as a useful tool at this time. There are a number of molecular imaging tools receiving attention at this time, namely 11 C-choline and 11C-acetate PET/CT, 18F-fluorocholine PET/CT, 18F-fluorocyclobutyl-1-carboxylic acid (FACBC) PET/CT, and new prostate-specific membrane antigen (PSMA)–targeting radiotracers. 11C-acetate PET/CT takes advantage of fatty acid synthase upregulation in prostate cancer14 and has little urinary excretion. Mena et al15 reported that the sensitivity and specificity is approximately 62% and 80%, respectively, and shows greatest benefit for detection of recurrence in advanced prostate cancer. In another study by Oyama et al,16 the reported detection rate is 59% with PSA4 3 ng/mL and 4% with o 3 ng/mL. Similarly, the choline radiotracers exploit the overexpression of choline kinase from cell proliferation in prostate cancer. Detection rate for recurrent disease is dependent on PSA level, and although a 44.1% positivity rate has been reported with PSA o1 ng/mL, detection rate increases to 88.5% with PSA 4 5 ng/mL.17 Currently these PET radiotracers are primarily used in the setting of recurrent disease and are under clinical trial at multiple institutions. 11C-choline is now FDA approved in limited settings, but the choline radiotracers are widely used outside of the United States. Another molecular imaging radiotracer 18F-FACBC is transported similar to glutamine, which is an important substrate for tumor metabolism. Schuster et al18 have reported on imaging of 115 patients with suspected recurrent prostate cancer, with a whole-body detection rate of 81.7%, though detection rate is also dependent on PSA level, with 39% detection with PSA between 0 and 1 ng/mL and greater than 90% with a PSA 4 2 ng/mL. Nanni et al19 studied 28 men with biochemical failure after prostatectomy where the mean PSA was 2.9 ng/mL. 11C-choline was compared with FACBC. In 5 patients, the 11C-choline was positive compared with 10 patients with the FACBC study, with better lesion conspicuity on FACBC PET. Turkbey et al reported that the addition of FACBC to MR increased the positive predictive value for detection of recurrent disease from 75% to 82%, suggesting that there may be utility in combining these imaging tools.20 Current clinical investigation includes prospective studies evaluating the role and effect on clinical decision of FACBC in the setting of recurrence after surgery, radiotherapy, and cryotherapy. Finally, new PSMA-targeting radiotracers such as 18F-N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-[18F]fluorobenzyl-L-cysteine, which targets the extracellular domain responsible for enzymatic activity,21 and 68Ga-PSMA22 are showing improved performance compared with 111 In-capromab pendetide and may represent a promising alternative to conventional imaging in the future. In conclusion, the detection of advanced prostate cancer remains a significant clinical challenge. Currently ultrasound, MRI, CT, and bone scans are mainstays of our diagnostic tools. 18F-NaF PET/CT is available today and FDA approved and has substantial data supporting its usage. Molecular imaging techniques, namely, 11C-choline and 11C-acetate PET/CT,
32
P.J. Rossi, D.M. Schuster / Curr Probl Cancer 39 (2015) 29–32
18 F-fluorocholine PET/CT, 18F-FACBC PET/CT, and new PSMA-targeting radiotracers, have shown promise and are an area of intense investigation at this time.
References 1. DeSantis CE, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin 2014;64(4):252–271. 2. Freedland SJ, et al. Upgrading and downgrading of prostate needle biopsy specimens: risk factors and clinical implications. Urology 2007;69(3):495–499. 3. Heijmink SW, et al. State-of-the-art uroradiologic imaging in the diagnosis of prostate cancer. Acta Oncol 2011; 50(suppl 1):25–38. 4. Turkbey B, et al. Imaging localized prostate cancer: current approaches and new developments. Am J Roentgenol 2009;192(6):1471–1480. 5. Murphy G, et al. The expanding role of MRI in prostate cancer. Am J Roentgenol 2013;201(6):1229–1238. 6. Turkbey B, Pinto PA, Choyke PL. Imaging techniques for prostate cancer: implications for focal therapy. Nat Rev Urol 2009;6(4):191–203. 7. Choueiri TK, et al. A model that predicts the probability of positive imaging in prostate cancer cases with biochemical failure after initial definitive local therapy. J Urol 2008;179(3):906–910. [discussion 910]. 8. Eberhardt SC, et al. ACR Appropriateness Criteria prostate cancer—pretreatment detection, staging, and surveillance. J Am Coll Radiol 2013;10(2):83–92. 9. Casalino DD, et al. ACR Appropriateness Criteria(R) posttreatment follow-up of prostate cancer. J Am Coll Radiol 2011;8(12):863–871. 10. Hinkle GH, et al. Multicenter radioimmunoscintigraphic evaluation of patients with prostate carcinoma using indium-111 capromab pendetide. Cancer 1998;83(4):739–747. 11. Schuster DM, et al. Characterization of primary prostate carcinoma by anti-1-amino-2-[(18)F] -fluorocyclobutane-1carboxylic acid (anti-3-[(18)F] FACBC) uptake. Am J Nucl Med Mol Imaging 2013;3(1):85–96. 12. Pfluger T, et al. Diagnostic value of combined 18F-FDG PET/MRI for staging and restaging in paediatric oncology. Eur J Nucl Med Mol Imaging 2012;39(11):1745–1755. 13. Even-Sapir E, et al. The detection of bone metastases in patients with high-risk prostate cancer: 99mTc-MDP Planar bone scintigraphy, single- and multi-field-of-view SPECT, 18F-fluoride PET, and 18F-fluoride PET/CT. J Nucl Med 2006;47(2):287–297. 14. Pfluger T, et al. Integrated imaging using MRI and 123I metaiodobenzylguanidine scintigraphy to improve sensitivity and specificity in the diagnosis of pediatric neuroblastoma. Am J Roentgenol 2003;181(4):1115–1124. 15. Mena E, et al. 11C-Acetate PET/CT in localized prostate cancer: a study with MRI and histopathologic correlation. J Nucl Med 2012;53(4):538–545. 16. Oyama N, et al. 11C-acetate PET imaging of prostate cancer: detection of recurrent disease at PSA relapse. J Nucl Med 2003;44(4):549–555. 17. Mitchell CR, et al. Operational characteristics of (11)C-choline positron emission tomography/computerized tomography for prostate cancer with biochemical recurrence after initial treatment. J Urol 2013;189(4):1308–1313. 18. Schuster DM, et al. Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography and (111)Incapromab pendetide single photon emission computerized tomography-computerized tomography for recurrent prostate carcinoma: results of a prospective clinical trial. J Urol 2014;191(5):1446–1453. 19. Nanni C, et al. 18F-FACBC compared with 11C-choline PET/CT in patients with biochemical relapse after radical prostatectomy: a prospective study in 28 patients. Clin Genitourin Cancer 2014;12(2):106–110. 20. Turkbey B, Mena E, Shih J, et al. Localized prostate cancer detection with 18F FACBC PET/CT: comparison with MR imaging and histopathologic analysis. Radiology 2014;270(3):849–856. doi: 10.1148/radiol.13130240. Epub 2013 Nov 8. 21. Cho SY, Gage KL, Mease RC, et al. Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a lowmolecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer. J Nucl Med 2012;53:1883. 22. Afshar-Oromieh A, et al. Comparison of PET imaging with a 68Ga-labelled PSMA ligand and 18F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2013;40:486.