Radiolabeling of VEGF165 with 99mTc to evaluate VEGFR expression in tumor angiogenesis

Abstract

Angiogenesis is the main process responsible for tumor growth and metastatization. The principal effector of such mechanism is the vascular endothelial growth factor (VEGF) secreted by cancer cells and other components of tumor microenvironment. Radiolabeled VEGF analogues may provide a useful tool to noninvasively image tumor lesions and evaluate the efficacy of anti-angiogenic drugs that block the VEGFR pathway. Aim of the present study was to radiolabel the human VEGF165 analogue with 99mTechnetium (99mTc) and to evaluate the expression of VEGFR in both cancer and endothelial cells in the tumor microenvironment. 99mTc-VEGF showed in vitro binding to HUVEC cells and in vivo to xenograft tumors in mice (ARO, K1 and HT29). By comparing in vivo data with immunohistochemical analysis of excised tumors we found an inverse correlation between 99mTc-VEGF165 uptake and VEGF histologically detected, but a positive correlation with VEGF receptor expression (VEGFR1). Results of our studies indicate that endogenous VEGF production by cancer cells and other cells of tumor microenvironment should be taken in consideration when performing scintigraphy with radiolabeled VEGF, because of possible false negative results due to saturation of VEGFRs.

Theranostic Designed Near-Infrared Fluorescent Poly (Lactic-co-Glycolic Acid) Nanoparticles and Preliminary Studies with Functionalized VEGF-Nanoparticles

“…Our study, showing high tumor accumulation of PLGA-NPs (with or without VEGF) within 24 h from injection, is preparatory for the development of radiolabeled NPs with diagnostic and/or therapeutic purposes, replacing the NIR-fluorescent probe. The use of radioisotopes, especially alfa or beta- emitters, poses a serious problem of liver and kidneys radiotoxicity and we believe that the added value of VEGF (or other targeting molecules) functionalization might mitigate this issue [ 45 , 46 ]. In this perspective, we selected for targeting studies the time point of 24 h p.i., as it matches with the half-life of most common diagnostic isotopes.…”

The Role of VEGF Receptors as Molecular Target in Nuclear Medicine for Cancer Diagnosis and Combination Therapy

“…[ 99m Tc]Tc-HYNIC-VEGF-A 165 radiocompound with unmodified VEGF-A 165 was evaluated for VEGFR expressions in various xenografts tumours in mice [ 181 ]. The authors admitted that studies with VEGF-based radiocompounds gave false negative results in the case of large tumours due to receptor saturation by in situ secreted VEGF glycoproteins.…”

A Radiolabeling Method for Precise Quantification of Polymers

“…Studies also suggest that this method shows a higher labeling efficiency and a more controllable conjugation ratio 3 compared to other iodine labeling methods like chloramine T, iodogen, and enzymatic methods. 6,7 ICl radiolabeling is achieved using either 125 I or 131 I isotopes through iodination of tyrosine and histidine within the protein structure. The most effective labeling group is the phenol group of tyrosine.…”

“…Radiolabeling has been extensively used in many areas of imaging, nuclear medicine, biomaterials research, and drug development. , Positron emission tomography and single-photon emission computed tomography play a pivotal role in monitoring the location, distribution, and accumulation of radiolabeled medicine and nanomaterials in living subjects. − The technique has also been widely used to provide accurate and precise protein quantification in biochemistry, biomaterials, pharmacology, and drug delivery research. − Since gamma counting can measure solid samples, this technique also allows for the tracking of protein distribution in tissues and other solid materials, both in the matrix and on the surface. For instance, radiolabeled proteins and peptides are frequently utilized as tracer molecules for quantitative determination, such as in the measurement of antigen antibody binding, as well as tracking metabolic movement of drug and protein adsorption on biomaterial surfaces, allowing for sensitive and accurate quantification of very low amounts of peptides or proteins.…”