Biodistribution and imaging of [99mTc]-HYNIC-RGD in MDA-MB-231 and NTERA-2 cancer cell xenografts.

Purpose: Increased expression of αvβ3 integrins is involved in tumour angiogenesis. Targeting these receptors with a dedicated peptide containing the RGD sequence may provide information about the receptor status in and around the tumour and about the angiogenesis process involved. The aim of this study was to compare the uptake of [Tc]-HYNIC-RGD in two types of tumours that either express or do not express the αvβ3 receptor (NTERA-2 and MDA-MB-231, respectively) and discuss the use of this tracer in experimental models of angiogenesis.
Procedures: Uptake of intravenously injected [Tc]-HYNIC-RGD was studied ex vivo and in vivo. Histological analysis of excised tumours was carried out. Percentages of the injected dose uptake per gram of tissue were compared between the two types of tumours and in the periphery and centre of each tumour.
Results: [Tc]-HYNIC-RGD was rapidly cleared from blood circulation and excreted through the kidneys. Residual activity was retained in the intestine. Tumour uptake of [Tc]-HYNIC-RGD was high and homogeneous for αvβ3-positive cell lines (1.94±0.26%ID/g). Tumour uptake was weak and distributed only in the tumour periphery for αvβ3-negative cell lines (0.10±0.02%ID/g, tumour periphery; 0.06±0.01%ID/g, tumour core; P=0.01). These results correlated with vessel distribution.
Conclusion: Uptake of [Tc]-HYNIC-RGD was more intense in αvβ3-positive cell lines than in αvβ3-negative cell lines, but tracer distribution was more representative of angiogenic locations in αvβ3-negative cell lines. Further clinical and preclinical studies are needed on the use of RGD-related tracers.