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

摘要

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_2TDMPP) and [~(175)Yb]YbCl_3 or [~(153)Sm]SmCl_3 in 12-24 h at 60 °C. 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) (logP = 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.