Development of radiolanthanide labeled porphyrin complexes as possible therapeutic agents in beast carcinoma xenografts

Abstract

Abstract Radiolabeled porphyrins are potential tumor avid radiopharmaceuticals because of their behaviour in the human body, ability to complex various radionuclides, water solubility, low toxicity etc. , in this work radio ytterbium/samarium porphyrin complexes have been developed. 175 Yb and 153 Sm labeled 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrins ([ 175 Yb]-TDMPP/[ 153 Sm]-TDMPP) were prepared using 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrin (H 2 TDMPP) and [ 175 Yb]YbCl 3 or [ 153 Sm]SmCl 3 in 12–24 h at 60 ℃. Stability of the complexes were checked in final formulation and human serum for 24 h, followed by partition coefficient determination and biodistribution studies in wild type and breast carcinoma-bearing mice. The radiocomplexes were obtained with acceptable radiochemical purity (> 95% (paper chromatography) and > 96% (HPLC) for [ 175 Yb]-TDMPP and > 97% (paper chromatography) and >98% (HPLC) for [ 153 Sm]-TDMPP) with specific activities of 12–15 GBq/mmol and 278 GBq/mmol at the end of bombardment for [ 175 Yb]-TDMPP and [ 153 Sm]-TDMPP respectively. The partition coefficients were determined for [ 175 Yb]-TDMPP and [ 153 Sm]-TDMPP) (log P = 0.63 and log P = 0.96 respectively). The [ 175 Yb]-TDMPP complex is mostly washed out from the circulation through kidneys. Liver and spleen also demonstrated significant activity uptake in 72 h post injection. Also [ 153 Sm]-TDMPP, is mostly washed out from the circulation through kidneys, however lungs are the major accumulation sites. The [ 153 Sm]-TDMPP complex demonstrated significant targeted uptake in breast carcinoma xenografts with tumor: blood ratios of 10.67, 10.47 and 19.01 in 24, 48 and 72 h respectively. Also interesting tumor: kidney/liver ratios were obtained. 153 Sm-TDMPP properties suggest an efficient tumor targeting agent with high tumor-avidity. Further investigation on the therapeutic properties must be conducted.