186Re-1,4,8,11-tetraaza cyclotetradecyl-1,4,8,11-tetramethylene phosphonic acid: a novel agent for possible use in metastatic bone-pain palliation.

In connection with our work on the development of 186Re-tetra-phosphonates with optimum properties for use in bone pain palliation, a novel cyclic tetraphosphonate derivative, has been synthesized, complexed with 186Re and evaluated with promising results. The ligand, which consists of a cyclic array of tetra-aminomethylphosphonate groups, was synthesized using orthophosphorus acid, 1,4,8,11-tetraazacyclotetradecane and formaldehyde. The labeling conditions with 186Re have been standardized under varying reaction conditions to give maximum yield. In a reaction volume of 1 mL, maximum complexation yield of 98% was observed at pH 2 using 0.1 mg Re (37-370 MBq) for a ligand concentration at 9 x 10(-2) M/L, under heating at 100 degrees C for 30 min with 2 mg of stannous chloride. The complex was found to be stable for 6 days with RC purity remaining approximately 97%. The complex was characterized by paper chromatography in saline and acetone, wherein the R(f) exhibited were 0.9 and 0, respectively. Biodistribution studies of the complex were performed in male Wistar rats. Activity in femur which was observed to be 1.8%/g (equivalent to about 23% of the injected activity in skeleton) at 3 h post injection remained almost constant up to 48 h. Minimum activity was observed in blood and other soft tissues. The complex showed major renal clearance. Scintigraphic images in rabbits after injecting 70-100 MBq of 186Re-CTMP and using a dual head gamma camera were observed to be superior to 186Re-HEDP, prepared by a procedure standardized by us. Insignificant activity was observed in other vital organs. The results suggest the suitability of the complex for further evaluation in higher animals for bone pain palliation.

Effect of radioiodine therapy on pulmonary alveolar-capillary membrane integrity.

UNLABELLED: The effects of large doses of radioiodine on the pulmonary alveolar-capillary membrane using 99mTc-DTPA clearance as an index of pulmonary damage in subjects with pulmonary metastases of differentiated thyroid carcinoma were studied. METHODS: Technetium-99m-DTPA radioaerosols were generated by a dry aerosol generator. Data were acquired and analyzed for clearance half-time from the lungs with a scintillation camera. The study was carried out on 35 thyroid cancer patients with pulmonary metastases and on 32 patients without metastases; the results were compared to those of a control group comprising 52 subjects. The radiation dose delivered to the lungs from the therapeutic dose was calculated using MIRD methodology. RESULTS: Cumulative radioiodine doses varied from 5.9 to 44.2 GBq (158-1194 mCi). The half-time clearance of 99mTc-DTPA was comparable in both patient groups and was not related to the total administered radioiodine dosage or to the radiation dose delivered to the lungs. No changes were observed for periods up to 5 yr after receiving the last radioiodine dosage. Seven patients followed at regular intervals from 6 mo to 2 yr did not show abnormal 99mTc-DTPA clearance values. One patient did show low 99mTc-DTPA clearance half-time values, which were symptomatic radiation pneumonitis. She had received a total dose of 34 GBq (922 mCi) over a 4-yr period. CONCLUSION: The incidence of pulmonary damage resulting from radioiodine therapy for lung metastases of differentiated thyroid cancer is negligible, as evidenced by the normal pulmonary clearance half-time of 99mTc-DTPA aerosols.