ABSTRACT
The radionuclides 43Sc, 44g/mSc, and 47Sc can be produced cost-effectively in sufficient yield for medical research and applications by irradiating natTi and natV target materials with protons. Maximizing the production yield of the therapeutic 47Sc in the highest cross section energy range of 24-70 MeV results in the co-production of long-lived, high-γ-ray-energy 46Sc and 48Sc contaminants if one does not use enriched target materials. Mass separation can be used to obtain high molar activity and isotopically pure Sc radionuclides from natural target materials; however, suitable operational conditions to obtain relevant activity released from irradiated natTi and natV have not yet been established at CERN-MEDICIS and ISOLDE. The objective of this work was to develop target units for the production, release, and purification of Sc radionuclides by mass separation as well as to investigate target materials for the mass separation that are compatible with high-yield Sc radionuclide production in the 9-70 MeV proton energy range. In this study, the in-target production yield obtained at MEDICIS with 1.4 GeV protons is compared with the production yield that can be reached with commercially available cyclotrons. The thick-target materials were irradiated at MEDICIS and comprised of metallic natTi, natV metallic foils, and natTiC pellets. The produced radionuclides were subsequently released, ionized, and extracted from various target and ion source units and mass separated. Mono-atomic Sc laser and molecule ionization with forced-electron-beam-induced arc-discharge ion sources were investigated. Sc radionuclide production in thick natTi and natV targets at MEDICIS is equivalent to low- to medium-energy cyclotron-irradiated targets at medically relevant yields, furthermore benefiting from the mass separation possibility. A two-step laser resonance ionization scheme was used to obtain mono-atomic Sc ion beams. Sc radionuclide release from irradiated target units most effectively could be promoted by volatile scandium fluoride formation. Thus, isotopically pure 44g/mSc, 46Sc, and 47Sc were obtained as mono-atomic and molecular ScF 2+ ion beams and collected for the first time at CERN-MEDICIS. Among all the investigated target materials, natTiC is the most suitable target material for Sc mass separation as molecular halide beams, due to high possible operating temperatures and sustained release.
ABSTRACT
Samarium-153 is a promising theranostic radionuclide, but low molar activities (Am) resulting from its current production route render it unsuitable for targeted radionuclide therapy (TRNT). Recent efforts combining neutron activation of 152Sm in the SCK CEN BR2 reactor with mass separation at CERN/MEDICIS yielded high-Am 153Sm. In this proof-of-concept study, we further evaluated the potential of high-Am 153Sm for TRNT by radiolabeling to DOTA-TATE, a well-established carrier molecule binding the somatostatin receptor 2 (SSTR2) that is highly expressed in gastroenteropancreatic neuroendocrine tumors. DOTA-TATE was labeled with 153Sm and remained stable up to 7 days in relevant media. The binding specificity and high internalization rate were validated on SSTR2-expressing CA20948 cells. In vitro biological evaluation showed that [153Sm]Sm-DOTA-TATE was able to reduce CA20948 cell viability and clonogenic potential in an activity-dependent manner. Biodistribution studies in healthy and CA20948 xenografted mice revealed that [153Sm]Sm-DOTA-TATE was rapidly cleared and profound tumor uptake and retention was observed whilst these were limited in normal tissues. This proof-of-concept study showed the potential of mass-separated 153Sm for TRNT and could open doors towards wider applications of mass separation in medical isotope production.
ABSTRACT
We performed the direct measurement of second harmonic generation and sum frequency generation phase-matching directions in the organic N-benzyl-2-methyl-4-nitroaniline crystal over its visible and near-infrared transparency range. The fit of these data allowed us to refine the Sellmeier equations of the three principal refractive indices in this range. With these equations, we improved the calculated tuning curves of terahertz emission from a phase-matched difference frequency process. We also determined the absolute magnitude of the d24 nonlinear coefficient.
