Rhenium-188 labelled meso-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl] porphyrin for targeted radiotherapy: preliminary biological evaluation in mice.

PURPOSE: This study focusses on a promising carrier system for therapeutic and imaging purposes using meso-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl] porphyrin (T(3,4)CPP). To assess its potential for clinical use, we labelled T(3,4)CPP with (188)Re and analysed some kinetic biodistribution parameters after intravenous injection in mice. MATERIALS AND METHODS: T(3,4)CPP was synthesized and labelled with (188)Re. Normal Kunming (KM) mice and melanoma- or hepatoma-bearing BALB/c nude mice were injected intravenously with 5.55 MBq (188)Re-labelled T(3,4)CPP and sacrificed at 0.5, 2, 4, and 24 h and 8, and 24 h, respectively. RESULTS: The (188)Re-T(3,4)CPP yield was more than 95% with specific activity 16.9 GBq (mol)(-1), and Vitamin C (VC) could increase its stability in vitro. In normal KM mice, (188)Re-T(3,4)CPP had fast blood clearance (approximately 99%, 24 h postinjection), low retention in the vital organs and hepatotropic characteristics. In nude mice, more than 4.4 and 6.1% uptake per gram of tumour (%ID g(-1)) at 8 h postinjection was in melanoma and hepatoma, respectively; this remained as high levels after 24 h as 4.6 and 6.5%, respectively. At 8 h, the tumour/blood and tumour/muscle (T/M) ratios in melanomas and hepatoma bearing mice were 7.3, 13,and 7.0, 20, respectively. Twenty-four hours later, these high ratios still continued in existence which were 9.6, 19 and 10, 25, respectively. CONCLUSION: The results obtained in this study indicate that (188)Re-T(3,4)CPP has better tumour affinity and retainable accumulation characteristics in carcinoma which can potentially be used for tumour-targeted radiotherapy.

Synthesis and preliminary biological studies of the novel conjugate 188Re-labeled meso-tetrakis(4-sulfophenyl)porphyrin in mice.

OBJECTIVE: The objective of this study was to evaluate the biological behaviors of a novel (188)Re-labeled meso-tetrakis(4-sulfophenyl)porphyrin (TPPS(4)) in normal mice and tumor-bearing mice. METHODS: TPPS(4) was synthesized and labeled by (188)ReO(4)(-). Normal KM mice and BALB/c nude mice bearing melanoma or hepatoma were prepared for distribution studies. RESULTS: The [(188)Re]TPPS(4) yield was >98% with a specific activity of 11.2 GBq/mol, and vitamin C could increase its stability in vitro. In normal KM mice, [(188)Re]TPPS(4) had a fast blood clearance ( approximately 90%, 24 h postinjection), low retention in vital organs and hepatotropic characteristics. In nude mice, uptakes of >4.1% and 6.5% ID/g tumor at 8 h postinjection were observed in melanoma and hepatoma, respectively; this remained at high levels of 4.7% and 5.7%, respectively, after 24 h. At 8 h, the tumor/blood and tumor/muscle ratios in melanoma-bearing and hepatoma-bearing mice were 6.2-15.2 and 6.1-24.2, respectively. Twenty-four hours later, these high ratios still continued at 8.6-22.1 and 12-26.1, respectively. CONCLUSION: The results obtained in this study indicate that [(188)Re]TPPS(4) has a high tumor affinity and retainable accumulation characteristics in carcinoma, which can potentially be used for tumor-targeted therapy.

Labeling conditions, in vitro properties and biodistributions of various Sn-labeled complexes.

Conditions for preparing Sn-EDTMP, Sn-DTPMP, Sn-TTHMP, Sn-HEDTMP and Sn-DTPA in aqueous solution in open air environments, and their in vitro properties including adsorption on hydroxyapatite (HA) and collagen (I) and binding to bovine serum albumin (BSA) were studied using (117m)Sn and 113Sn as tracers. Biodistributions of SnO2.xH2O.yEDTMP, SnO2.xH2O.yDTPMP, SnO2.xH2O.yTTHMP, SnO2.xH2O.yHEDTMP, SnO2.xH2O.yDTPA in normal mice were also tested. Based on the above experiments, the relationship between in vitro biochemical properties and biodistributions of these SnO2.xH2O.yLigands was investigated. The results show that Sn(IV)-Ligands are prone to hydrolysis into SnO2.xH2O.yLigands in aqueous solutions in open air environments, especially when the ligand is DTPA, when the molar ratio of metal to ligand is higher than 1:200, or when the pH of the solution is higher than 10. The in vitro experiments show that all of the SnO2.xH2O.yLigands bind strongly to BSA, and the binding percentages of SnO2.xH2O.yLigands to BSA are much higher than those of the corresponding Sn(IV)-Ligands. The biodistribution data indicate that all of the SnO2.xH2O.yLigands locate mainly in bone with little uptake in liver. When the binding percentages of SnO2.xH2O.yLigands to BSA are similar, those SnO2.xH2O.yLigands with higher adsorption on HA and collagen (I) undergo lower liver uptake.