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


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.


CONCLUSIONS
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.
Jia
Zhi-yun
ZY
Department of Nuclear Medicine, West China Hospital, Sichuan University, Wuhou District, Chengdu, Sichuan Province 610041, China. zhiyunjia@hotmail.com
Deng
Hou-fu
HF
Pu
Man-fei
MF
Luo
Shun-zhong
SZ
D000818:Animals; D004195:Disease Models, Animal; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008113:Liver Neoplasms / Q000532:radiotherapy; D008114:Liver Neoplasms, Experimental / Q000532:radiotherapy; D008545:Melanoma / Q000532:radiotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011166:Porphyrins / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D012211:Rhenium / Q000627:therapeutic use*; D014018:Tissue Distribution
D009942:Organometallic Compounds; D011166:Porphyrins; D019275:Radiopharmaceuticals; C442104:rhenium meso-tetrakis(3,4-bis(carboxymethyleneoxy)phenyl)porphyrin; D012211:Rhenium