O.P.D. Noronha

A new 99mTc labeled porphyrin for specific imaging of Sarcoma 120: Synthesis and biological study in a Swiss mouse model

A new porphyrin meso-5,10,15,20-tetrakis(3,4-bis(carboxymethyleneoxyphenyl)porphyrin (T3,4BCPP) was synthesised and efficiently labeled with 99m Tc. on injecting this 99m Tc labeled porphyrin to abdominal Sarcoma 120 bearing Swiss mice it accumulated in the abdominal tumour. This radiolabeled complex can thus be used for tumour detection and diagnosis.

Preparation and biological evaluation of the new chlorin photosensitizer T3,4BCPC for detection and treatment of tumors

The new water-soluble photosensitizer 5,10,15,20-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl]chlorin (T3,4BCPC) has been prepared, characterized and labeled with 99mTc radionuclide. The radiotracer was evaluated for tissue distribution in Wistar rats. Accumulation of administrated activities in the liver, kidney, bladder and large intestine at 4 h post-injection indicated that the labeled ligand was largely eliminated through the renal and partly through the hepatobiliary system. In vivo biodistribution studies of the labeled compound were carried out in rodent and murine tumor models in comparison with other tumor-seeking radiopharmaceuticals such as 99mTc(V)-dimercaptosuccinic acid (DMSA), 201thallous chloride (TlCl) and 99mTc-citrate using a gamma camera computer system. In N-nitrosomethylurea (NMU)-induced rat mammary tumors, the labeled ligand showed a five-fold tumor to muscle (T/M) ratio compared to 99mTc(V)-DMSA (3-fold) and 201TlCl (3-fold). In the case of C(3)H/J virus-induced spontaneous mammary tumors, the differences were not marked. However, in the transplanted rat C(6)-glioma, the T/M ratio of the labeled compound was appreciably higher (four-fold) than that noted with 99mTc(V)-DMSA (two-fold), 201TlCl (three-fold) and 99mTc-citrate (more than three-fold). These findings suggest that the radiolabeled T3,4BCPC may have potential for the detection of cancer. In order to ascertain the efficacy of the compound for photodynamic therapy applications, a preclinical PDT study was carried out in fibrosarcoma-bearing mice after injecting 5.0 mg/kg body weight of the T3,4BCPC. A laser dose of 20 mW for 60 s resulted in 80% destruction of tumors. These data suggest that this molecule could be useful for PDT of cancer. The labeled agent could also be useful in monitoring the progression/regression of tumors before, during, and after chemotherapy, radiation therapy or PDT.

Factors affecting the preparation of 99mTc-sulfur colloid.

Some factors, such as the effect of mannitol as ‘stabilizer’, increased concentration of thiosulfate, autoclaving conditions, etc., that can affect the preparation of 99mTc-sulfur colloid and consequently its biodistribution into different tissues are discussed. Also discussed are parameters, such as distribution with respect to time, effect of storage, preloading dose, etc., that can influence the uptake of the radiopharmaceutical by the RES in animals and humans.

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

SummaryHuman 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.

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.

The phenomenon of ‘tired moly-99Mo’

The phenomenon of ‘tired moly-99Mo’ results in poor yields of 99mTcO4-obtained from 99MoO42-. The solvated electron has been conceived to explain this phenomenon, especially when it occurs in highly alkaline media as obtained in the solvent extraction type of separation system.