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|Title: ||Preparation and biological evaluation of the new chlorin photosensitizer T3,4BCPC for detection and treatment of tumors|
|Authors: ||MURUGESAN, S|
|Keywords: ||photodynamic therapy|
|Issue Date: ||2002|
|Publisher: ||ELSEVIER SCIENCE SA|
|Citation: ||JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 68(1), 33-38|
|Abstract: ||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 Tc-99m 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 Tc-99m(V)-dimercaptosuccinic acid (DMSA), (201)thallous chloride (TlCl) and Tc-99m-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 Tc-99m(V)-DMSA (3-fold) and (TlCl)-Tl-201 (3-fold). In the case of C3H/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 Tc-99m(V)-DMSA (two-fold), (TlCl)-Tl-201 (three-fold) and Tc-99m-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. (C) 2002 .|
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