Evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab as a radioimmunotherapy agent targeting VEGF expressing cancers

• Published in: Applied radiation and isotopes Vol. 114; pp. 196 - 201
• Main Authors: Kameswaran, Mythili, Pandey, Usha, Gamre, Naresh, Vimalnath, K V, Sarma, Haladhar Dev, Dash, Ashutosh
• Format: Journal Article
• Language: English
• Published: England 01-08-2016
• Subjects: Animals; Bevacizumab - pharmacokinetics; Bevacizumab - therapeutic use; Cell Line, Tumor; Humans; Immunoconjugates - isolation & purification; Immunoconjugates - pharmacokinetics; Immunoconjugates - therapeutic use; Lutetium - pharmacokinetics; Lutetium - therapeutic use; Melanoma, Experimental - metabolism; Melanoma, Experimental - radiotherapy; Mice; Mice, Inbred C57BL; Pentetic Acid - analogs & derivatives; Pentetic Acid - pharmacokinetics; Pentetic Acid - therapeutic use; Radioimmunotherapy - methods; Radioisotopes - pharmacokinetics; Radioisotopes - therapeutic use; Radiopharmaceuticals - isolation & purification; Radiopharmaceuticals - pharmacokinetics; Radiopharmaceuticals - therapeutic use; U937 Cells; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - immunology; Vascular Endothelial Growth Factor (VEGF); Lu-CHX-A′′-DTPA-Bevacizumab; Melanoma; Bevacizumab
• ISSN: 1872-9800
• DOI: 10.1016/j.apradiso.2016.05.025

This study aimed at the preparation and evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab for targeting VEGF over-expressing cancers. Bevacizumab conjugated to p-NCS-Bn-CHX-A''-DTPA was radiolabeled with (177)Lu. The radioimmunoconjugate characterized by SE-HPLC exhibited radiochemical purity of 98.0±0.6%. In vitro stability was retained upto 4 days at 37°C. In vitro cell binding studies showed good uptake by VEGF expressing U937 tumor cells. Biodistribution studies in melanoma model showed significant uptake and retention of (177)Lu-CHX-A''-DTPA-Bevacizumab in tumor with reduction in uptake in presence of cold Bevacizumab confirming its specificity to VEGF.