Evaluation of 99m Tc-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.