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

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. ¹⁷⁵Yb and ¹⁵³Sm labeled 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrins ([¹⁷⁵Yb]-TDMPP/[¹⁵³Sm]-TDMPP) were prepared using 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrin (H₂TDMPP) and [¹⁷⁵Yb]YbCl₃ or [¹⁵³Sm]SmCl₃ 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 [¹⁷⁵Yb]-TDMPP and > 97% (paper chromatography) and >98% (HPLC) for [¹⁵³Sm]-TDMPP) with specific activities of 12–15 GBq/mmol and 278 GBq/mmol at the end of bombardment for [¹⁷⁵Yb]-TDMPP and [¹⁵³Sm]-TDMPP respectively. The partition coefficients were determined for [¹⁷⁵Yb]-TDMPP and [¹⁵³Sm]-TDMPP) (log P = 0.63 and log P = 0.96 respectively). The [¹⁷⁵Yb]-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 [¹⁵³Sm]-TDMPP, is mostly washed out from the circulation through kidneys, however lungs are the major accumulation sites. The [¹⁵³Sm]-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. ¹⁵³Sm-TDMPP properties suggest an efficient tumor targeting agent with high tumor-avidity. Further investigation on the therapeutic properties must be conducted.