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

• Published in: European journal of nuclear medicine and molecular imaging 2008-04, Vol.35 (4), p.734-742
• Main Authors: Jia, Zhi-yun, Deng, Hou-fu, Pu, Man-fei, Luo, Shun-zhong
• Format: Article
• Language: English
• Subjects: Animals; Cancer; Cardiology; Disease Models, Animal; Drug Stability; Hydrogen-Ion Concentration; Imaging; Kinetics; Liver Neoplasms - radiotherapy; Liver Neoplasms, Experimental - radiotherapy; Medicine; Medicine & Public Health; Melanoma - radiotherapy; Mice; Mice, Inbred BALB C; Mice, Nude; Nuclear Medicine; Oncology; Organometallic Compounds - blood; Organometallic Compounds - pharmacokinetics; Organometallic Compounds - therapeutic use; Original Article; Orthopedics; Pharmaceuticals; Porphyrins - blood; Porphyrins - pharmacokinetics; Porphyrins - therapeutic use; Radiation therapy; Radiology; Radiopharmaceuticals - therapeutic use; Rhenium - therapeutic use; Rodents; Tissue Distribution
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-007-0682-0

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 (~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.