title: Biologic evaluation of a novel 188Re-labeled porphyrin in mice tumor model.
abstract: The aim of this study was to develop a (188)Re-labeled porphyrin-based tumor-specific agent and to evaluate its biologic behavior, including tumor-regressing effectiveness, in mouse tumor models for possible use in achieving targeted cancer radiotherapy. (188)Re was obtained from an alumina-column-based (188)W-(188)Re generator constructed in-house. The compound, 5,10,15,20-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl]porphyrin, was synthesized and labeled with (188)ReO(4)(-). (188)Re-labeled porphyrin complex was produced with a radiochemical purity of approximately 98% with reasonably good in vitro stability (>24 hours at 4 degrees C). Swiss mice bearing thymic lymphoma and fibrosarcoma were used as tumor models. The biodistribution studies revealed satisfactory tumor retention (2.07% +/- 0.80% injected activity per g) with insignificant activities in blood (0.53%), liver (0.26%) and kidney (0.04%) at 24 hours. The radiolabeled conjugate treatment increased the average tumor-doubling time and decreased the average specific growth rate substantially in thymic lymphoma, compared to fibrosarcoma tumor. (188)Re-labeled 5,10,15,20-tetrakis[3,4 bis(carboxymethyleneoxy)phenyl] porphyrin has specific affinity toward the fibrosarcoma and thymic lymphoma tumors in mice. Thymic lymphoma was found to be more sensitive to the radionuclide complex, compared to fibrosarcoma. The (188)Re-labeled porphyrin complex showed promising results and warrants further investigations.
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India.
authors.forename: Haladhar D
authors.initials: HD
authors.lastname: Sarma
authors.forename: Tapas
authors.initials: T
authors.lastname: Das
authors.forename: Sharmila
authors.initials: S
authors.lastname: Banerjee
authors.forename: Meera
authors.initials: M
authors.lastname: Venkatesh
authors.forename: Pandit B
authors.initials: PB
authors.lastname: Vidyasagar
authors.forename: Kaushala P
authors.initials: KP
authors.lastname: Mishra
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D007553:Isotope Labeling / Q000379:methods; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011868:Radioisotopes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013953:Thymus Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D014018:Tissue Distribution
chemical_list: D009942:Organometallic Compounds; D011166:Porphyrins; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C442104:rhenium meso-tetrakis(3,4-bis(carboxymethyleneoxy)phenyl)porphyrin