Activity standard and calibrations for 227Th with ingrowing progeny.

Thorium-227 was separated from its progeny and standardized for activity by the triple-to-double coincidence ratio (TDCR) method of liquid scintillation counting. Confirmatory liquid scintillation-based measurements were made using efficiency tracing with 3H and live-timed anticoincidence counting (LTAC). The separation time and the efficiency of the separation were confirmed by gamma-ray spectrometry. Calibrations for reentrant pressurized ionization chambers, including commercial radionuclide calibrators, and a well-type NaI(Tl) detector are discussed.

Efficient Synthesis and HPLC-Based Characterization for Developing Vanadium-48-Labeled Vanadyl Acetylacetonate as a Novel Cancer Radiotracer for PET Imaging.

Bis(acetylacetonato)oxidovanadium(IV) [(VO(acac)2], generally known as vanadyl acetylacetonate, has been shown to be preferentially sequestered in malignant tissue. Vanadium-48 (48V) generated with a compact medical cyclotron has been used to label VO(acac)2 as a potential radiotracer in positron emission tomography (PET) imaging for the detection of cancer, but requires lengthy synthesis. Current literature protocols for the characterization of VO(acac)2 require macroscale quantities of reactants and solvents to identify products by color and to enable crystallization that are not readily adaptable to the needs of radiotracer synthesis. We present an improved method to produce vanadium-48-labeled VO(acac)2, [48V]VO(acac)2, and characterize it using high-performance liquid chromatography (HPLC) with radiation detection in combination with UV detection. The approach is suitable for radiotracer-level quantities of material. These methods are readily applicable for production of [48V]VO(acac)2. Preliminary results of preclinical, small-animal PET studies are presented.

A TOPAS model for lens-based proton radiography.

Objective.Proton Radiography can be used in conjunction with proton therapy for patient positioning, real-time estimates of stopping power, and adaptive therapy in regions with motion. The modeling capability shown here can be used to evaluate lens-based radiography as an instantaneous proton-based radiographic technique. The utilization of user-friendly Monte Carlo program TOPAS enables collaborators and other users to easily conduct medical- and therapy- based simulations of the Los Alamos Neutron Science Center (LANSCE). The resulting transport model is an open-source Monte Carlo package for simulations of proton and heavy ion therapy treatments and concurrent particle imaging.Approach.The four-quadrupole, magnetic lens system of the 800-MeV proton beamline at LANSCE is modeled in TOPAS. Several imaging and contrast objects were modelled to assess transmission at energies from 230-930 MeV and different levels of particle collimation. At different proton energies, the strength of the magnetic field was scaled according toßγ,the inverse product of particle relativistic velocity and particle momentum.Main results.Materials with high atomic number, Z, (gold, gallium, bone-equivalent) generated more contrast than materials with low-Z (water, lung-equivalent, adipose-equivalent). A 5-mrad collimator was beneficial for tissue-to-contrast agent contrast, while a 10-mrad collimator was best to distinguish between different high-Z materials. Assessment with a step-wedge phantom showed water-equivalent path length did not scale directly according to predicted values but could be mapped more accurately with calibration. Poor image quality was observed at low energies (230 MeV), but improved as proton energy increased, with sub-mm resolution at 630 MeV.Significance.Proton radiography becomes viable for shallow bone structures at 330 MeV, and for deeper structures at 630 MeV. Visibility improves with use of high-Z contrast agents. This modality may be particularly viable at carbon therapy centers with accelerators capable of delivering high energy protons and could be performed with carbon therapy.

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.

Modelling cyclotron-based production of radioisotopes via TOPAS.

Objective. In this work, the irradiation of natural titanium foils in the beam-stop of a compact medical cyclotron, an IBA CYCLONE 18/9, is simulated to assess the efficacy of using a beam-stop as a target holder, and using two different target geometries, in the production of vanadium-48, a positron-emitting radioisotope with potential utility as a cancer imaging agent in positron emission tomography.Approach. TOPAS, the TOol for PArticle Simulation, a Geant4-based Monte Carlo program, was used to model the cyclotron beam parameters, choose an appropriate physics list, and simulate the irradiation of targets made from foils of 12 or 12.5µm thickness. These simulation yields were compared to theoretical yields calculated using cross section data from the literature, as well as assayed yields from experimental irradiations.Main results.We found that most physics lists in TOPAS overestimate the cross section in the desired energy range (16-20 MeV) by at least 136%, with the exception of those using the Bertini Cascade Model. Compared to assayed yields, TOPAS provided a minimum of 0.4% error for cup-shaped targets and at least a 12% overestimation for sphere-shaped targets.Significance.These simulations provide a tool to help explain irregularities in radioisotope production yield and motivate modifications to increase target yield.

Preliminary investigation of 48V-labeled VO(acac)2 for cancer imaging: An initial proof-of-concept study.

In this preliminary study, a procedure for synthesizing novel PET radiotracer vanadium-48-labeled-vanadyl acetylacetonate was developed, including radioisotope production via cyclotron, separation of 48V, chelation as 48VO(acac)2, and assessment through in vitro cellular studies. We employed the beam-stop setup in a cyclotron as the target holder to irradiate titanium foils in the reaction of natTi (p,n)48V. The radioisotope production rate was 4.84 ± 0.67 µCi/µA-h. Overall radiochemical yield was 12.86 ± 0.51% with gamma-ray spectroscopy showing no detectable contaminant peaks. HPLC of 48VO(acac)2 showed a retention time (1:48) corresponding closely to that (1:50) of commercial VO(acac)2, verifying the successful synthesis of 48VO(acac)2. In vitro cellular studies demonstrated radiotracer uptake and saturation around 0.48 nM. These studies pave the way for improving methodologies and in vivo experiments, including imaging studies, in future investigations.

Contrast-enhanced proton radiographic sensitivity limits for tumor detection.

Purpose: Proton radiography may guide proton therapy cancer treatments with beam's-eye-view anatomical images and a proton-based estimation of proton stopping power. However, without contrast enhancement, proton radiography will not be able to distinguish tumor from tissue. To provide this contrast, functionalized, high- Z nanoparticles that specifically target a tumor could be injected into a patient before imaging. We conducted this study to understand the ability of gold, as a high- Z , biologically compatible tracer, to differentiate tumors from surrounding tissue. Approach: Acrylic and gold phantoms simulate a tumor tagged with gold nanoparticles (AuNPs). Calculations correlate a given thickness of gold to levels of tumor AuNP uptake reported in the literature. An identity, × 3 , and × 7 proton magnifying lens acquired lens-refocused proton radiographs at the 800-MeV LANSCE proton beam. The effects of gold in the phantoms, in terms of percent density change, were observed as changes in measured transmission. Variable areal densities of acrylic modeled the thickness of the human body. Results: A 1 - µ m -thick gold strip was discernible within 1 cm of acrylic, an areal density change of 0.2%. Behind 20 cm of acrylic, a 40 - µ m gold strip was visible. A 1-cm-diameter tumor tagged with 1 × 10 5 50-nm AuNPs per cell has an amount of contrast agent embedded within it that is equivalent to a 65 - µ m thickness of gold, an areal density change of 0.63% in a tissue thickness of 20 cm, which is expected to be visible in a typical proton radiograph. Conclusions: We indicate that AuNP-enhanced proton radiography might be a feasible technology to provide image-guidance to proton therapy, potentially reducing off-target effects and sparing nearby tissue. These data can be used to develop treatment plans and clinical applications can be derived from the simulations.