ORIGINAL ARTICLES   

The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2014 June;58(2):224-33

Copyright © 2014 EDIZIONI MINERVA MEDICA

language: English

Synthesis and biological evaluation of 177Lu-DOTA-porphyrin conjugate: a potential agent for targeted tumor radiotherapy

Bhadwal M. ¹, Mittal S. ¹, Das T. ¹, Sarma H. D. ², Chakraborty S. ¹, Banerjee S. ¹, Pillai M. R. ¹ ✉

¹ Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai India; ² Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai India

A novel unsymmetrically substituted water soluble porphyrin derivative namely, 5-(p-amino­propylene­­oxyphenyl)-10,15,20-tris-(p-carboxy­methyl­ene­oxyphenyl)porphyrin was synthesized and coupled with a bifunctional chelating agent, viz. p-NCS-benzyl-DOTA (p-isothiocyanatobenzyl-1,4,7,10-tetra­aza­cyclodo­decane-1,4,7,10-tetra­acetic acid) for developing a suitable conjugate for use in targeted tumor therapy. The porphyrin-p-NCS-benzyl-DOTA conjugate was radiolabeled with 177Lu in good radiolabeling yield. Biodistribution studies performed in Swiss mice bearing fibrosarcoma tumors revealed high tumor uptake (5.33±1.11% injected activity per gm of tumor) within 30 min post-injection. The complex exhibited favorable tumor to blood and tumor to muscle ratios at various post-administration time points. Fast clearance of the non-accumulated activity was observed mostly through the renal pathway. Scintigraphic imaging studies performed in Swiss mice bearing fibrosarcoma tumors also exhibited selective accumulation of activity in the tumor.