Evaluation of 99mTc-Labeled Bevacizumab-N-HYNIC Conjugate in Human Ovarian Tumor Xenografts.

Abstract

Aim: The aim of the present investigation was to examine the suitability of 99mTc-N-HYNIC-BZMB as a specific vascular endothelial growth factor (VEGF)-targeting agent. Bevacizumab is a recombinant humanized monoclonal antibody that inhibits VEGF. Methods: N-hydroxysuccinimide-2-hydrazinonicotinic acid (N-HYNIC) was conjugated to BZMB, followed by labeling with 99mTc using N-[Tris(hydroxymethyl)methyl] glycine (tricine), ethylenediamine-N,N'-diacetic acid (EDDA), and nicotinic acid as coligands. 99mTc-labeled BZMB was characterized in terms of 99mTcO4, radiocolloids, and labeled N-HYNIC-BZMB using thin-layer chromatography and HPLC. Poor metastatic SKOV-3 and high metastatic SKOV-3.ip1 human ovarian cancer cell lines were used for in vitro binding uptake of 99mTc-N-HYNIC-BZMB. Biodistribution and scintigraphy accuracy were examined in human ovarian tumor xenografts in rats and rabbits. Results: 99mTc-N-HYNIC-BZMB prepared by using a mixture of tricine and EDDA demonstrated relatively high radiochemical purity (more than 98%). In L-cysteine and serum, it exhibited a stable behavior up to 16 h. In vitro binding uptake indicated that it targets high metastatic SKOV-3.ip1 tumors. Biodistribution in human ovarian tumor xenografts in rats confirmed a significant uptake in SKOV-3.ip1 tumors (5.69% ± 1.86%, 4 h). Scintigraphic accuracy in human ovarian tumor xenografts in rabbits validated its suitability as a high metastatic SKOV-3.ip1 radiotracer. Conclusion: High radiochemical purity, stability in saline and serum, biodistribution, and scintigraphy of 99mTc-N-HYNIC-BZMB in human ovarian tumor xenografts in rats and rabbits confirmed its suitability as a potential radiotracer for imaging high metastatic SKOV-3.ip1 sites.