Studies on the preparation and stability of samarium-153 propylene diamine tetramethylene phosphonate (PDTMP) complex as a bone seeker.

Propylene diamine tetra methylene phosphonate (PDTMP) was synthesised by modifying a method reported for the synthesis of EDTMP. Complexation of the synthesised phosphonate ligand with 153Sm was carried out by varying the experimental parameters and the complex was radiochemically characterized. Biodistribution studies showed that the uptake by bone in rats was 2% per g of bone, which was retained upto 48 h. The uptake by other organs was insignificant, except by the liver which showed a slightly higher absorption.

Preparation of [186Re]Re-DMSA and its bio-distribution studies.

99mTc(V)-DMSA is widely used for imaging medullary carcinoma and hence 186/188Re(V)-DMSA is suggested as a potential agent for treating medullary carcinoma. In the present paper, we report the work carried out for the preparation of [186Re]Re(V)-DMSA and it's bio-distribution studies in Wistar rats. The complex was prepared by reducing 186Re (100 micrograms, 0.54 microM, approximately 150 MBq) in the presence of DMSA (2 mg, 11 microM) with stannous chloride (0.4 mg, 2.2 microM) in acidic medium at pH 2. The reaction was taken to completion by heating the complex in a boiling water bath for 30 min. Bio-distribution studies carried out revealed that pharmacological behaviour of 186Re(V)-DMSA is similar to that of 99mTc(V)-DMSA except that the kidney uptake is marginally higher. The kidney uptake reduced significantly when the pH of the complex was adjusted to 8 prior to injection. The in vitro stability studies of this complex suggest that the product formed is stable and could be used for clinical trials.

Preparation, stability studies and pharmacological behavior of [186Re]Re-HEDP.

99mTc-HEDP is widely used as a bone imaging agent and its Re analog [186Re]Re-HEDP is now well established as a therapeutic radiopharmaceutical for palliation of pain due to bone metastases. In the present paper, we report the work carried out for the preparation of stable 186Re-HEDP which retains RC purity up to 5 days when stored at 4 degrees C. 186Re was prepared by irradiation of natural Re metal at a flux of 3 x 10(13) neutrons/cm2/s for seven days and processed after a cooling period of four days. The specific activity of 186Re formed was approximately 35 mCi/mg. A complex with RC purity > 98% could be prepared by varying the reaction conditions. By carefully optimizing the reaction and storage conditions, a complex which was stable for over 4 days could be synthesized. Bio-distribution studies carried out in rats revealed approximately 30% bone uptake of 186Re-HEDP at 3 h postinjection which remained almost constant for 48 h, at which time there was negligible activity in other organs.

Evaluation of 99Tcm-labelled human immunoglobulin in animal models of experimentally induced inflammatory lesions.

Human immunoglobulin (HIG) was labelled with 99Tcm using different Sn-ligand (methylene diphosphonate, MDP) in high yields. The effect of Sn:ligand ratios and protein (HIG) on the biodistribution pattern of 99Tcm-HIG in an animal model of turpentine-induced inflammatory lesions was studied. 99Tcm-HIG was excreted predominantly via the renal pathway. The use of higher amounts of MDP and HIG resulted in relatively slower blood clearance and increased uptake of 99Tcm-HIG in various organs. Also, higher amounts of ligand [Sn:MDP (1:5)] resulted in significantly greater bone uptake (P < 0.001), while protein caused slower blood clearance and greater liver uptake. Despite the increased uptake of tracer in various organs, the ratio of inflamed:normal muscle uptake did not change significantly. A scintigraphic study was carried out with both 99Tcm-HIG and 99Tcm labelled with human serum albumin (HSA) in turpentine-induced inflammatory lesions produced in rabbits. The study revealed no significant differences in uptake early on, but the target:non-target ratio was higher with 99Tcm-HIG at 24 h. 99Tcm-HIG also had superior characteristics compared with 99Tcm-HSA.

Biokinetics of 99mTc-labelled liver-imaging agents in an animal model of liver cirrhosis.

Comparable degree of liver cirrhosis, as judged by liver function tests and histopathology, was induced in rats by carbon tetrachloride. Comparative organ distribution of 99mTc-sulphur colloid and 99mTc-phytate was studied in the liver, spleen and lungs of these cirrhotic rats. Compared to controls, the biodistribution of 99mTc-sulphur colloid was found to be affected more than that of 99mTc-phytate in cirrhotic rats, especially at early time intervals.

Binding of 99Tcm sulphur colloid to blood components: implications in renal transplant rejection.

The percentage binding of 99Tcm sulphur colloid to blood components (formed elements and plasma proteins) was studied within 1 min of the intravenous injection of the radiopharmaceutical in humans as well as rats. In humans, 68% of the total blood counts were bound to the formed elements (erythrocytes, leucocytes and platelets). The binding pattern (as percentage of plasma counts) among the plasma protein fractions in humans was as follows: albumin, 9.85 +/- 2.06; fibrinogen, 56.70 +/- 7.96; and total proteins, 66.55 +/- 7.32. Activity bound to fibrinogen represented 82.3 +/- 9.1% of the total protein-bound activity in humans. In rats as well fibrinogen was the predominant binding protein (73.8 +/- 5.6). The significant binding of the 99Tcm sulphur colloid to plasma fibrinogen and formed elements of blood may be one of the reasons for the uptake of this radiocolloid in renal transplants before rejection.