44Sc-DOTA-BN[2-14]NH2 in comparison to 68Ga-DOTA-BN[2-14]NH2 in pre-clinical investigation. Is 44Sc a potential radionuclide for PET?

In the present study we demonstrate the in vitro and in vivo comparison of the 44Sc and 68Ga labeled DOTA-BN[2-14]NH2. 44Sc is a positron emitter with a half life of 3.92h. Hence it could be used for PET imaging with ligands requiring longer observation time than in the case of 68Ga. The binding affinity of natSc-DOTA-BN[2-14]NH2 and natGa-DOTA-BN[2-14]NH2 to GRP receptors was studied in competition to [125I-Tyr4]-Bombesin in the human prostate cancer cell line PC-3. A preliminary biodistribution in normal rats was performed, while first microPET images were assessed in male Copenhagen rats bearing the androgen-independent Dunning R-3327-AT-1 prostate cancer tumor. The affinity to GRP receptors in the PC-3 cell line was higher for natGa-DOTA-BN[2-14]NH2 (IC50(nM)=0.85±0.06) than that of natSc-DOTA-BN[2-14]NH2 (IC50 (nM)=6.49±0.13). The internalization rate of 68Ga labeled DOTA-BN[2-14]NH2 was slower than that of 44Sc, but their final internalization percents were comparable. 68Ga-DOTA-BN[2-14]NH2 was externalized faster than 44Sc-DOTA-BN[2-14]NH2. The biodistribution of 44Sc-DOTA-BN[2-14]NH2 and 68Ga-DOTA-BN[2-14]NH2 in normal rats revealed a higher uptake in target organs and tissues of the first one while both excreted mainly through urinary tract. In microPET images both tracers were accumulated in the tumor with similar uptake patterns. Despite the differences in the receptor affinity both the 68Ga- and the 44Sc-labeled DOTA-BN[2-14]NH2 tracers showed comparable distribution and similar time constants of uptake and elimination. Moreover no differences in tumor accumulation (neither in the overall uptake nor in the dynamics) were observed from the microPet imaging. From that perspective the use of either 44Sc or 68Ga for detecting tumors with GRP receptors is equivalent. ► In vitro and in vivo evaluation of 44Sc- and 68Ga-DOTA-BN[2-14]NH2 in reference to published data. ► Higher in vitro affinity to GRP receptors (PC-3 cells) for natGa-DOTA-BN[2-14]NH2. ► Both showed similar internalization rates, however the efflux rate of the 44Sc analog was lower. ► 68Ga- and 44Sc-DOTA-BN[2-14]NH2 showed no differences in tumor accumulation. ► Hence the use of either 44Sc or 68Ga for detecting tumors with GRPR is equivalent.