Sc for labeling of DOTA- and NODAGA-functionalized peptides: preclinical in vitro and in vivo investigations.

BACKGROUND

Recently, Sc (T = 3.97 h, Eβ = 632 keV, I = 94.3 %) has emerged as an attractive radiometal candidate for PET imaging using DOTA-functionalized biomolecules. The aim of this study was to investigate the potential of using NODAGA for the coordination of Sc. Two pairs of DOTA/NODAGA-derivatized peptides were investigated in vitro and in vivo and the results obtained with Sc compared with its Ga-labeled counterparts.DOTA-RGD and NODAGA-RGD, as well as DOTA-NOC and NODAGA-NOC, were labeled with Sc and Ga, respectively. The radiopeptides were investigated with regard to their stability in buffer solution and under metal challenge conditions using Fe and Cu. Time-dependent biodistribution studies and PET/CT imaging were performed in U87MG and AR42J tumor-bearing mice.

RESULTS

Both RGD- and NOC-based peptides with a DOTA chelator were readily labeled with Sc and Ga, respectively, and remained stable over at least 4 half-lives of the corresponding radionuclide. In contrast, the labeling of NODAGA-functionalized peptides with Sc was more challenging and the resulting radiopeptides were clearly less stable than the DOTA-derivatized matches. Sc-NODAGA peptides were clearly more susceptible to metal challenge than Sc-DOTA peptides under the same conditions. Instability of Ga-labeled peptides was only observed if they were coordinated with a DOTA in the presence of excess Cu. Biodistribution data of the Sc-labeled peptides were largely comparable with the data obtained with the Ga-labeled counterparts. It was only in the liver tissue that the uptake of Ga-labeled DOTA compounds was markedly higher than for the Sc-labeled version and this was also visible on PET/CT images. The Sc-labeled NODAGA-peptides showed a similar tissue distribution to those of the DOTA peptides without any obvious signs of in vivo instability.

CONCLUSIONS

Although DOTA revealed to be the preferred chelator for stable coordination of Sc, the data presented in this work indicate the possibility of using NODAGA in combination with Sc. In view of a clinical study, thorough investigations will be necessary regarding the labeling conditions and storage solutions in order to guarantee sufficient stability of Sc-labeled NODAGA compounds.