Production of high purity Sc from proton irradiation of natural vanadium targets.

Background: Scandium-47 is the therapeutic counterpart to the diagnostic radionuclides, Sc and Sc. Together, these form elementally matched theranostic nuclide pairs, but their incorporation into radiopharmaceuticals requires developing production techniques leading to radioscandium isotopes with high chemical and radionuclidic purity. Previous Sc production methods involved expensive, enriched titanium targets that require additional procedures for target recovery.

Cross section measurements for the production of Cr and Sc from proton irradiation of natural vanadium up to 24 MeV.

Scandium-47 is a promising radionuclide for targeted radiotherapy and is also an elementally matched therapeutic partner to Sc and Sc, which are suitable for Positron Emission Tomography. The predominantly reported routes for the production of Sc employ expensive enriched titanium or calcium targets to achieve high radionuclidic purity. This study reports measurements of the excitation function of the V(p,x)Sc reaction at proton energies of 18-24 MeV to optimize bombardment parameters for the production of Sc using this promising approach.

Production and separation of Be for use in an ion source.

Beryllium-7 (Be) was created by proton irradiation of natural (B) and enriched (B) boron targets. The targets were dissolved in nitric acid, and the Be was separated from the bulk boron target material by cation-exchange chromatography. An average recovery of (99.

Construction of the Bioconjugate Py-Macrodipa-PSMA and Its In Vivo Investigations with Large La and Small Sc Radiometal Ions.

To harness radiometals in clinical settings, a chelator forming a stable complex with the metal of interest and targets the desired pathological site is needed. Toward this goal, we previously reported a unique set of chelators that can stably bind to both large and small metal ions, via a conformational switch. Within this chelator class, py-macrodipa is particularly promising based on its ability to stably bind several medicinally valuable radiometals including large La, Bi, and small Sc.

Evaluation of a novel hexadentate 1,2-hydroxypyridinone-based acyclic chelate, HOPO-O-C4, for Sc/Sc, Ga, and Ti radiopharmaceuticals.

Introduction: Chelators play a crucial role in the development of metal-based radiopharmaceuticals, and with the continued interest in Ga and increasing availability of new radiometals such as Sc/Sc and Ti, there is a growing demand for tailored chelators that can form stable complexes with these metals. This work reports the synthesis and characterization of a hexadentate tris-1,2-hydroxypyridonone chelator HOPO-O-C4 and its in vitro and in vivo evaluation with the above mentioned radiometals.

Methods: To investigate the affinity of HOPO-O-C4, macroscopic studies were performed with Sc, and Ga followed by DFT structural optimization of the Sc, Ga and Ti complexes.

Production and purification of Sc and Sc from enriched [Ti]TiO and [Ti]TiO targets.

The radioscandium isotopes, Sc and Sc, compose a promising elementally matched theranostic pair that can be used for the development of imaging and therapeutic radiopharmaceuticals with identical structures. This study aimed to investigate the production of high radionuclidic purity Sc from enriched [Ti]TiO targets and Sc from enriched [Ti]TiO targets and establish a target recycling technique. Enriched [Ti]TiO targets were irradiated with 18 MeV protons, and enriched [Ti]TiO targets were bombarded with 24 MeV protons.

Evaluation of [Zr]Zr-DFO-2Rs15d Nanobody for Imaging of HER2-Positive Breast Cancer.

One of the most aggressive forms of breast cancer involves the overexpression of human epidermal growth factor receptor 2 (HER2). HER2 is overexpressed in ∼25% of all breast cancers and is associated with increased proliferation, increased rates of metastasis, and poor prognosis. Treatment for HER2-positive breast cancer has vastly improved since the development of the monoclonal antibody trastuzumab (Herceptin) as well as other biological constructs.

Sc-HOPO: A Potential Construct for Use in Radioscandium-Based Radiopharmaceuticals.

Three isotopes of scandium─Sc, Sc, and Sc─have attracted increasing attention as potential candidates for use in imaging and therapy, respectively, as well as for possible theranostic use as an elementally matched pair. Here, we present the octadentate chelator 3,4,3-(LI-1,2-HOPO) (or HOPO), an effective chelator for hard cations, as a potential ligand for use in radioscandium constructs with simple radiolabeling under mild conditions. HOPO forms a 1:1 Sc-HOPO complex that was fully characterized, both experimentally and theoretically.

Evaluation of Lu and Sc Picaga-Linked, Prostate-Specific Membrane Antigen-Targeting Constructs for Their Radiotherapeutic Efficacy and Dosimetry.

Lu-177-based, targeted radiotherapeutics/endoradiotherapies are an emerging clinical tool for the management of various cancers. The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) remains the workhorse for such applications but can limit apparent molar activity or efficient charge modulation, which can impact target binding and, as a consequence, target efficacy. Previously, our lab had developed the small, rare earth selective bifunctional chelator, picaga, as an efficient bifunctional chelator for scandium and lutetium isotopes.

Accelerator Production of Scandium Radioisotopes: Sc-43, Sc-44, and Sc-47.

Scandium radioisotopes are increasingly considered viable radiolabels for targeted molecular imaging (Sc-43, Sc-44) and therapy (Sc-47). Significant technological advances have increased the quantity and quality of available radioscandium in the past decade, motivated in part by the chemical similarity of scandium to therapeutic radionuclides like Lu-177. The production and radiochemical isolation techniques applied to scandium radioisotopes are reviewed, focusing on charged particle and electron linac initiated reactions and using calcium and titanium as starting materials.

Homologous Structural, Chemical, and Biological Behavior of Sc and Lu Complexes of the Picaga Bifunctional Chelator: Toward Development of Matched Theranostic Pairs for Radiopharmaceutical Applications.

The radioactive isotopes scandium-44/47 and lutetium-177 are gaining relevance for radioimaging and radiotherapy, resulting in a surge of studies on their coordination chemistry and subsequent applications. Although the trivalent ions of these elements are considered close homologues, dissimilar chemical behavior is observed when they are complexed by large ligand architectures due to discrepancies between Lu(III) and Sc(III) ions with respect to size, chemical hardness, and Lewis acidity. Here, we demonstrate that Lu and Sc complexes of 1,4-bis(methoxycarbonyl)-7-[(6-carboxypyridin-2-yl)methyl]-1,4,7-triazacyclononane (Hmpatcn) and its corresponding bioconjugate picaga-DUPA can be employed to promote analogous structural features and, subsequently, biological properties for coordination complexes of these ions.