44Sc for labeling of DOTA- and NODAGA-functionalized peptides: preclinical in vitro and in vivo investigations

Domnanich, Katharina Anna; Müller, Cristina; Farkas, Renata; Schmid, Raffaella M.; Ponsard, Bernard; Schibli, Roger; Türler, Andreas; van der Meulen, Nicholas P. (2016). 44Sc for labeling of DOTA- and NODAGA-functionalized peptides: preclinical in vitro and in vivo investigations. EJNMMI Radiopharmacy and Chemistry, 1(1), p. 8. Springer 10.1186/s41181-016-0013-5

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Recently, 44Sc (T1/2 = 3.97 h, Eβ+ av = 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 44Sc. Two pairs of DOTA/NODAGA-derivatized peptides were investigated in vitro and in vivo and the results obtained with 44Sc compared with its 68Ga-labeled counterparts.

DOTA-RGD and NODAGA-RGD, as well as DOTA-NOC and NODAGA-NOC, were labeled with 44Sc and 68Ga, respectively. The radiopeptides were investigated with regard to their stability in buffer solution and under metal challenge conditions using Fe3+ and Cu2+. Time-dependent biodistribution studies and PET/CT imaging were performed in U87MG and AR42J tumor-bearing mice.

Both RGD- and NOC-based peptides with a DOTA chelator were readily labeled with 44Sc and 68Ga, respectively, and remained stable over at least 4 half-lives of the corresponding radionuclide. In contrast, the labeling of NODAGA-functionalized peptides with 44Sc was more challenging and the resulting radiopeptides were clearly less stable than the DOTA-derivatized matches. 44Sc-NODAGA peptides were clearly more susceptible to metal challenge than 44Sc-DOTA peptides under the same conditions. Instability of 68Ga-labeled peptides was only observed if they were coordinated with a DOTA in the presence of excess Cu2+. Biodistribution data of the 44Sc-labeled peptides were largely comparable with the data obtained with the 68Ga-labeled counterparts. It was only in the liver tissue that the uptake of 68Ga-labeled DOTA compounds was markedly higher than for the 44Sc-labeled version and this was also visible on PET/CT images. The 44Sc-labeled NODAGA-peptides showed a similar tissue distribution to those of the DOTA peptides without any obvious signs of in vivo instability.

Although DOTA revealed to be the preferred chelator for stable coordination of 44Sc, the data presented in this work indicate the possibility of using NODAGA in combination with 44Sc. 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 44Sc-labeled NODAGA compounds.

Item Type:

Journal Article (Original Article)


08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)
10 Strategic Research Centers > Albert Einstein Center for Fundamental Physics (AEC)
08 Faculty of Science > Physics Institute > Laboratory for High Energy Physics (LHEP)

UniBE Contributor:

Domnanich, Katharina Anna, Schibli, Roger, Türler, Andreas


500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry
500 Science > 530 Physics








Franziska Bornhauser-Rufer

Date Deposited:

24 Jan 2017 09:39

Last Modified:

05 Dec 2022 15:01

Publisher DOI:






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