Measurement of 75SeSodium selenite in the human body

Work in progress

30

It appears that the distribution pattern of lutetium is similar to that of other rare earths; thus, HOLZER and GENSICKE(‘found ) a similar distribution pattern after administration of promethium-147. Moreover, the incidence of fatty liver was noted by LEHMANN,“’ after administration of stable praseodymium (3 mg/kg body-weight). The author noted a significant decrease of the cytochromes in the endoplasmic reticulum as early as 24hr after i.v. injection of rare earths. The long range effect of the I “Lu retained in the skeleton is being studied. Preliminary results showed an increased incidence of osteosarcoma in animals examined 12 months after administration of the rare earth; the overall absorbed radiation dose was estimated at 2000-8000rad. These results are similar to the production of osteosarcoma induced by “Sr.(”

60

50

50

% Skeleton

30

\

Department of Radiobiology and Biophysics, Department of Experimental

I

20-

W. A. MUELLER U. LINZNER E. H. SCHAFER

Pathology, Institute of Biology, D-8042 Neuherberg, Ingolstadter Landstrasse 1> German Federal Republic

IO-

Ayy ./t 0

0.5

I

mg/kQ

corrter

15

2

FIG. 3. Amount of total injection activity in skeleton and liver (in per cent plus standard errors) as a function of added stable lutetium carrier. Incorporation period: 8 days. The localization of the radionudde in the bone, spleen, kidney and liver was investigated by radioautography in the animals examined at 48 hr after i.p. injection. Figure 4 shows the distribution of “‘Lu in the distal end of the femur. Both endosteum and periosteum show a heavy retention of radionuclide, diffuse as well as in hot spots. Figure 5 shows the distribution of “‘Lu in the vertebra. The radionuclide is present in granules lining up the entire spongy bone; the spleen contains a rather large amount of radioactivity in the red pulp (Fig. 6), while the kidney displays a massive concentration of radioactive material in renal cortex (Fig. 7a) as well as in numerous hot spots in the papillary region of renal medulla (Fig. 7b). Finally, Fig. 8 shows the pattern of hepatic deposition, also in diffuse small grains as well as hot spots. Discussion The results of the experiment are in agreement with the data published by GLAUBITT.‘~) who, however, found a higher retention of “‘Lu in the skeleton (up to 90%). This difference could be ascribed to the chemical compounds used as carriers, chloride instead of citrate and especially the route of administration, intravenous in the experiments of Glaubitt. The retention of “‘Lu by the liver is comparable to that of plutonium which seems to be polymerized before the hepatic uptake. The fact that the hepatic retention of radiolutetium is higher in animals treated with higher amounts of stable carrier seems to sup port this hypothesis.

(In association with Euratom.) References

1. O’MARA R. E., MCAFEEJ. G. and SUBRAMANIAN G. J. nucl. Med. 10, 49 (1969). W. M., BERG 2. KYKER G. C., CHRISTOPHERSON H. F. and BRUCERM. Cancer 9, 1123 (1956). 3. IAEA. A Basic Toxicity ClassiJication of Radionuclides. Tech. Rep. Ser. No. 15, Vienna (1963). 4. HINDRINGERB. and BUSING G. Histochemie 26, 333 (1971). 5. STATHERJ. W. Hlth. Phys. 26, 71 (1974). 6. GLAUBIT? D. M. H., ROEDLERH. D. and MARX R. S. Proc. 5th lnt. Conf: Radiat. Res.. p. 86.

Seattle, WA. (1974). HOLTZERF. and GENSICKEF. Z. Naturf: 21b. 575 (1966). LEHMANNB. V., OBERDI~SE E., GRAJEVSKI0. and ARNTZ H. R. Archs Tox. 34, 89 (1975). VAUGHAN J. M. The EjJects of Irradiation on the

Skeleton, p. 154. Clarendon

Press, Oxford (1973).

International Journal or Nuclear Medwe and 30-34. Pergamon Press. Prmted I” Great Bntaln

Bmlogy.

1978. Vol.

5. pp

Measurement of ’%e-Sodium Selenite in the Human Body (Received 5 April 1977) 75!k-~~~~~ selenite was first used by ESTEBANet al.“’ in the diagnosis of a bone tumour, and its useful-

ness in the diagnosis of malignant tumours has been confirmed by other investigators.“A’ As interest in ‘%e-selenite scintigraphy has increased during the last few years, the investigators undertook a study to examine the accumulation of “Se-selenite in the

FIG. 4. Sagittal section of femur, haemalaun 16 x . (60 mCi/kg ’“Lu and 1 mg/kg stable carrier.) FIG. 5. Sagittal section of lumbar vertebra, haemalaun stable carrier.) FIG. 6. Section of spleen, haemalaun

16x. (20mCi/kg

FIG. 7. (a) kidney cortex and (b) medulla, haemalaun stable carrier.)

40 x . (60 mCi/kg “‘Lu

and 1 mg/kg

17’Lu and 5 mg/kg stable carrier.) 40 x

FIG. 8. Section of a central area of liver, haemalaun 100 x stable carrier.)

(60 mCi/kg “‘Lu

and 1 mg/kg

(20mCikg

and 5 mg/kg

“‘Lu

Work in progress

33

TABLE I. Percentage accumulation of “Se-sodium selenite in human tissues 14 days after administration of 75Se

Tissue ___ Muscle Liver Blood Kidneys Skin Brain Spleen Other organs -__

Accumulation (%) 30 17 15 7 6 4 2 19

human body and to estimate the absorbed doses by different organs in six patients with malignant tumours which received 300&i of selenite for scintigraphy. External measurements were made with a conventional thyroid iodine uptake system, collimated scintillation detector. pulse height analyzer and scaler. The activity of blood, urine, faeces and tissue samples was measured by standard dilution technique. The measurements of “Se accumulation in different organs are listed in Table 1. The calculation of the tissue retention curves, the absorbed doses in the target organs and the mean effective half-life was performed with a NOVA 1220 digital computer. The total absorbed doses by different organs evaluated after the schemas proposed by LOEV~NGER and BERMAN’“)and CL~LJ~ERet al.‘“’ are presented in Table 2. Excretion of 75Se-sodium selenite through the kidneys was about 3.3% in the first 24 hr, after which the rate of excretion rapidly decreased (Fig. 1). A small amount of selenite (approx. 0.24.3x) was recovered in the faeces during the first 24 hr, after which the excretion became minimal. Since there are reports in the literature of the elimination of selenite through the lungs in the form of dimethylselenide [Se(CH,)&“*s’ the following experiment was carried out: immediately after the injection. the patient breathed into a solution of 10% HgC12 + 20% HCl (Diginelli’s solution) for a period of 10 min. The exhalation of selenite was slight, certainly less than 0.1%. TABLE:2. Calculated absorbed dose of “Se-sodium selenite in different organs

Tissue Liver Kidney (right) Kidney (left) Spleen Testes Blood (whole) Whole body

Absorbed dose +_ error (mrad/&i “Se) 29& 10 27 _+ 11 25_+ 11 24 + 7 11 f3 8_+2 8+2

FIG. I. Excretion of “Se-sodium time. +. measured; *. calculated;

selenite against x, agreement.

The activity was 5-8 times greater in tumour specimens than in healthy tissue measured from biopsy samples 1 day after the injection of 75Se. The tumour/ subcutaneous tissue ratio was 6.3 +_ 1.2. In the present investigation, the mean effective halflife of “Se in tumour tissue was 80 days, 38 days in the liver and 37 days in the kidneys. The corresponding figures obtained by WENZEL et al.“” were not very different, viz. 71, 50 and 32 days. It would seem that selenite is retained in the tumour longer (80 days) than in healthy tissue (3540 days). This fact is beneficial for tumour imaging after several days. The abundant accumulation of selenite in the liver and kidneys disturbs the scanning of abdominal organs with selenite. The accumulation of selenite in the blood vessels is slight and does not interfere with scintigraphy of the thoracic cage, the extremities and the head and neck. Other radiop&rarmaceuticals used in tumour diagnosis have a better tumour/normal tissue ratio than “Seselenite (6.3 + 1.2) e.g. 67Ga-citrate.“0’ However, it seems that the tumour specificity of “Se selenite is more reliable”’ than that of 67Gacitrate.” ‘.I 2, The relative large radiation dose to the liver and the kidneys due to the long half-life of “Se prevents the use of “Se-sodium selenite in routine examination of young patients. Department of Radiotherapy, Central Hospital of Central Finland, SF-40620Jyviiskylii 62. Finland

J. KUIKKA E. NORDMAN

References

1. ESTEBAN J., LANA D. and PEREZ-M•DREC~;O S. Radiology 85, 149 (1965). 2. CAVALIERIR. R. and SCOTT K. G. In Proc. Int. Nucl. Med. Symp., London, p. 74 (1967). 3. FREDERIKSEN P. B. and MUNK J. Nord. Med. 80, 905 (1968). 4. NORDMANE. Acta Radial. Suppl. 340 (1974).

34

Work

in progress

5. LOEVINGER R. and BERMAN M. MIRD Pamphlet No. 1. J. nucl. Med. SuppL 1, (1968). 6. CLOUTIER R. J., WATSON E. E., ROHRER R. H. and

SMITH E. M. J. nucl. Mrd. 14, 53 (1973). 7. IMBACH A. and STERNBERGJ. Int. J. appl. Radiar.

“Cr- in vitro labelled erythrocytes. ment of red cell volume. “SI-albumin. for the measurement partment.

for the measureof plasma com-

isotopes 18, 545 (1967). 8. MELDOLESI U. and MOMBELLI L. J. nucl. Med. 15,

Material and Methods

30 (1971). 9. WENZEL M., Oreo R. and RIEHLE I. lnt. J. appl. Radial. Isotopes 22, 361 (1971). 10. EMRICH D.. M~HLEN A. VON ZUR, WILLGEROTH F. and LAMMICH A. Acta Radiol. ther. Phys. Biol. 11. 566 (1972). 11. LANGHAMMER H.. GLAUBITT G., GREBE S. F.. HAMPE J. E., HAUBOLD U., HER G., KAUL A.. KOEPPE P., KOPPENHAGENJ.. ROEDLER H. D. and VAN DER SCHIST J. B.. J. nucl. Med. 13, 25 (1972).

12. BLAIR W. H., CARROLL M., CARR E. A. JR. and FEKETY F. R. J. nucl. Med. 14, 99 (1973).

Metabolic

Fate of

” ‘Indium

in the Rat

(Recrivrd 15 June 1977)

Introduction

Male Wistar rats weighing between 200 and 300g and fed on a standard diet were used. The following products were injected intravenously: I’ ‘InCl, (10 pCi/lOO g) together with s9FeC1, (2 &i/l00 g) or 9’Tc”‘-colloids’7’ (2 @i/l00 g; Kit TCK 1, CEA Saclay. France; dia. of colloidal micelles = 400 A). “Cr in vitro labelled erythrocytes(*) and ‘251-a1bumin (0.1 pCi/lOO g; Centre National de Transfusion Sanguine, Orsay. France). Tissue distrihcrtion

qf ” ‘In in normal rats

At 6, 18. 48, 72 and 16@hr after isotope injection the rats were anaesthetized and tissue and organ samples obtained: liver. spleen. skin, muscle. lungs. small and large intestines. heart, stomach, kidneys and one femur. Six to 9 ml of blood were obtained by cardiac puncture. The samples were washed and weighed and their radioactivities were expressed as a percentage of the total radioactivity found in all organs and tissue samples. Comparison

between tissue concentration that of orher radioactive markers

’’‘In and

of

PREVIOUSstudies suggested that indium could be used as an irl Guo marker in the investigation of the erythropoietic bone marrow. This was mainly based upon clinical data”.” as well as the in uiuo and in vitro uptake by transferrin. ‘3.4’ However. there are some conflicting data against this possibility. such as the lack of incorporation of “‘In into haem or haemoglobin”) as well as the small proportion of the label found in the circulating erythrocytes of the rat. Five days after injection of ” ‘indium chloride, only 1.2% of the label remained in the circulating red cells.‘h’ In the present study. we tried to define the metabolic fate of ” ‘indium and to compare its tissular distribution to that of ‘9Fe chloride; additional tracers were used. such as: 99Tcm-colloids, marking the reticula-endothelial system,

Rats given “‘InC& and ‘9FeC1, were sacrificed 48 hr after injection and rats given ‘ICr labelled erythrocytes. 99Tc”‘-colloids and L251-albumin were sacrificed 1. 2 and 48 hr after isotope injection. Animals were anaesthetized with ether and the carotid artery was cannulated. A blood sample was taken and the thoracic aorta was then perfused with 500 ml of Tyrode solution containing 12,500 units of heparin. using a peristaltic pump adjusted to a flow rate of lOOml/min. Slight oedema occurred at the outflow site of the perfusate from the carotid artery, and this technique gave most organs free of visible blood. The tissue radioactivity was expressed as the number of counts remaining after subtraction of the residual vascular radioactivity as measured by “Cr

TABLE 1. Distribution

of normal

of ” ’InCl,

Time (hr) Skeleton Spleen Liver Skin Muscle Lungs (2) Heart Stomach Large and small intestines Kidneys (2) Blood

in the main organs

6 5.9 0.4 8.8 11.2 19.8 2.5 1.3 0.8

+ * * + k _t + k

18 2.4 0.2 3.1 3.0 3.9 0.2 0.3 0.2

7.3 + 3.0 I .o & 0.5 14.7 + 4.9 22.1 * 2.1 27.5 + 3.8 2.6 + 0.3 0.5 f 0.2 0.6 5 0.2

6.6 + 0.3 5.3 * 0.3 37.4 _t 6.0

9.4 + 0.4 1.5 + 0.4 12.8 f 2.5

rats as a function

48 7.8 0.8 18.1 17.5 20.4 1.0 0.4 0.9

_t + + + + _t * f

of time after infusion

72 3.2 0.5 6.6 1.5 4.2 0.2 0.1 0.2

8.1 + 0.4 6.5 f 0.2 8.5 + 2.0

8.6 1.8 16.5 25.4 27.4 1.3 0.3 1.6

+ + + * + * + )

160 3.4 0.7 5.4 1.3 3.6 0.1 0.1 0.3

7.7 ) 0.3 6.1 + 0.2 3.3 f 1.5

8.3 1.4 14.5 35.7 24.0 1.0 0.4 0.6

+ * f + f * + t_

3.2 0.7 5.2 5.8 2.0 0.2 0.1 0.2

4.2 + 0.2 9.0 + 0.2 0.9 + 0.4