Comparison of two new angiogenesis PET tracers 68Ga-NODAGA-E[c(RGDyK)]2 and 64Cu-NODAGA-E[c(RGDyK)]2; in vivo imaging studies in human xenograft tumors.

Abstract: Introduction: The aim of this study was to synthesize and perform a side-by-side comparison of two new tumor-angiogenesis PET tracers 68Ga-NODAGA-E[c(RGDyK)]2 and 64Cu-NODAGA-E[c(RGDyK)]2 in vivo using human xenograft tumors in mice. Human radiation burden was estimated to evaluate potential for future use as clinical PET tracers for imaging of neo-angiogenesis. Methods: A 68Ge/68Ga generator was used for the synthesis of 68Ga-NODAGA-E[c(RGDyK)]2. 68Ga and 64Cu labeled NODAGA-E[c(RGDyK)]2 tracers were administrated in nude mice bearing either human glioblastoma (U87MG) or human neuroendocrine (H727) xenograft tumors. PET/CT scans at 3 time points were used for calculating the tracer uptake in tumors (%ID/g), integrin αVβ3 target specificity was shown by blocking with cold NODAGA-E[c(RGDyK)]2, and biodistribution in normal organs were also examined. From biodistribution data in mice human radiation-absorbed doses were estimated using OLINDA/EXM software. Results: 68Ga-NODAGA-E[c(RGDyK)]2 was synthesized with a radiochemical purity of 89%–99% and a specific activity (SA) of 16–153MBq/nmol. 64Cu-NODAGA-E[c(RGDyK)]2 had a purity of 92%–99% and an SA of 64–78MBq/nmol. Both tracers showed similar uptake in xenograft tumors 1h after injection (U87MG: 2.23 vs. 2.31%ID/g; H727: 1.53 vs. 1.48%ID/g). Both RGD dimers showed similar tracer uptake in non-tumoral tissues and a human radiation burden of less than 10mSv with an administered dose of 200MBq was estimated. Conclusion: 68Ga-NODAGA-E[c(RGDyK)]2 and 64Cu-NODAGA-E[c(RGDyK)]2 can be easily synthesized and are both promising candidates for PET imaging of integrin αVβ3 positive tumor cells. 68Ga-NODAGA-E[c(RGDyK)]2 showed slightly more stable tumor retention. With the advantage of in-house commercially 68Ge/68Ga generators, 68Ga-NODAGA-E[c(RGDyK)]2 may be the best choice for future clinical PET imaging in humans. [Copyright &y& Elsevier]