Evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab as a radioimmunotherapy agent targeting VEGF expressing cancers.
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.
Isotope Production & Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India. Electronic address: kmythili@barc.gov.in.
Mythili
M
Kameswaran
Isotope Production & Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
Usha
U
Pandey
Isotope Production & Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
Naresh
N
Gamre
Isotope Production & Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
K V
KV
Vimalnath
Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
Haladhar Dev
HD
Sarma
Isotope Production & Applications Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
Ashutosh
A
Dash
D000818:Animals; D000068258:Bevacizumab / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D018796:Immunoconjugates / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000627:therapeutic use; D008187:Lutetium / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000378:metabolism / Q000532:radiotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020298:U937 Cells; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000276:immunology
D018796:Immunoconjugates; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D008187:Lutetium; D004369:Pentetic Acid; C000615061:Lutetium-177; C000607322:N-(2-amino-3-(para-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N,N',N',N'-pentaacetic acid
(177)Lu-CHX-A′′-DTPA-Bevacizumab; Bevacizumab; Melanoma; Vascular Endothelial Growth Factor (VEGF)