Accelerator-Based Production of Scandium Radioisotopes for Applications in Prostate Cancer: Toward Building a Pipeline for Rapid Development of Novel Theranostics.

In the field of nuclear medicine, the ß+ -emitting 43Sc and ß- -emitting 47Sc are promising candidates in cancer diagnosis and targeted radionuclide therapy (TRT) due to their favorable decay schema and shared pharmacokinetics as a true theranostic pair. Additionally, scandium is a group-3 transition metal (like 177Lu) and exhibits affinity for DOTA-based chelators, which have been studied in depth, making the barrier to implementation lower for 43/47Sc than for other proposed true theranostics. Before 43/47Sc can see widespread pre-clinical evaluation, however, an accessible production methodology must be established and each isotope's radiolabeling and animal imaging capabilities studied with a widely utilized tracer. As such, a simple means of converting an 18 MeV biomedical cyclotron to support solid targets and produce 43Sc via the 42Ca(d,n)43Sc reaction has been devised, exhibiting reasonable yields. The NatTi(γ,p)47Sc reaction is also investigated along with the successful implementation of chemical separation and purification methods for 43/47Sc. The conjugation of 43/47Sc with PSMA-617 at specific activities of up to 8.94 MBq/nmol and the subsequent imaging of LNCaP-ENZaR tumor xenografts in mouse models with both 43/47Sc-PSMA-617 are also presented.

Imaging and dosimetric characteristics of 67 Cu.

In recent years the use of beta-emitting radiopharmaceuticals for cancer therapy has expanded rapidly following development of therapeutics for neuroendocrine tumors, prostate cancer, and other oncologic malignancies. One emerging beta-emitting radioisotope of interest for therapy is 67Cu (t1/2: 2.6 d) due to its chemical equivalency with the widely-established positron-emitting isotope 64Cu (t1/2: 12.7 h). In this work we evaluate both the imaging and dosimetric characteristics of 67Cu, as well as producing the first report of SPECT/CT imaging using 67Cu. To this end, 67Cu was produced by photon-induced reactions on isotopically-enriched 68Zn at the Low-Energy Accelerator Facility (LEAF) of Argonne National Laboratory, followed by bulk separation of metallic 68Zn by sublimation and radiochemical purification by column chromatography. Gamma spectrometry was performed by efficiency-calibrated high-purity germanium (HPGe) analysis to verify absolute activity calibration and establish radionuclidic purity. Absolute activity measurements corroborated manufacturer-recommended dose-calibrator settings and no radionuclidic impurities were observed. Using the Clinical Trials Network anthropomorphic chest phantom, SPECT/CT images were acquired. Medium energy (ME) SPECT collimation was found to provide the best image quality from the primary 185 keV gamma emission of 67Cu. Reconstructed images of 67Cu were similar in quality to images acquired using 177Lu. Recovery coefficients were calculated and compared against quantitative images of 99mTc, 177Lu, and 64Cu within the same anthropomorphic chest phantom. Production and clinical imaging of 67Cu appears feasible, and future studies investigating the therapeutic efficacy of 67Cu-based radiopharmaceuticals are warranted.