First-in-Human PET/CT Imaging of Metastatic Neuroendocrine Neoplasms with Cyclotron-Produced 44Sc-DOTATOC: A Proof-of-Concept Study

⁴⁴Sc is a promising positron emission tomography (PET) radionuclide (T_1/2 = 4.04 hours, E_β+average = 632 keV) and can be made available, using a cyclotron production route, in substantial quantities as a highly pure product. Herein, the authors report on a first-in-human PET/CT study using ⁴⁴Sc-DOTATOC prepared with cyclotron-produced ⁴⁴Sc. The production of ⁴⁴Sc was carried out through the ⁴⁴Ca(p,n)⁴⁴Sc nuclear reaction at Paul Scherrer Institut, Switzerland. After separation, ⁴⁴Sc was shipped to Zentralklinik Bad Berka, Germany, where radiolabeling was performed, yielding radiochemically pure ⁴⁴Sc-DOTATOC. Two patients, currently followed up after peptide receptor radionuclide therapy of metastatic neuroendocrine neoplasms, participated in this proof-of-concept study. Blood sampling was performed before and after application of ⁴⁴Sc-DOTATOC. PET/CT acquisitions, performed at different time points after injection of ⁴⁴Sc-DOTATOC, allowed detection of even very small lesions on delayed scans. No clinical adverse effects were observed and the laboratory hematological, renal, and hepatic profiles remained unchanged. In this study, cyclotron-produced ⁴⁴Sc was used in the clinic for the first time. It is attractive for theranostic application with ¹⁷⁷Lu, ⁹⁰Y, or ⁴⁷Sc as therapeutic counterparts. ⁴⁴Sc-based radiopharmaceuticals will be of particular value for PET facilities without radiopharmacy, to which they can be shipped from a centralized production site.