Optimized production, purification, and radiolabeling of the Pb/Pb theranostic pair for nuclear medicine.

TRIUMF is one of the only laboratories in the world able to produce both lead-203 (Pb, t = 51.9 h) and Pb (t = 10.6 h) onsite via its 13 and 500 MeV cyclotrons, respectively.

Determination of distribution coefficients of mercury and gold on selected extraction chromatographic resins - towards an improved separation method of mercury-197 from proton-irradiated gold targets.

Radioisotope mercury-197g (Hg, half-life: 64.14 h) along with its metastable isomer (Hg, half-life: 23.8 h) are potential candidates for targeted Meitner-Auger electron therapy due to their suitable decay properties.

Synthesis of DOTA-pyridine chelates for Cu coordination and radiolabeling of αMSH peptide.

Background: Cu is one of the few radioisotopes that can be used for both imaging and therapy, enabling theranostics with identical chemical composition. Development of stable chelators is essential to harness the potential of this isotope, challenged by the presence of endogenous copper chelators. Pyridyl type chelators show good coordination ability with copper, prompting the present study of a series of chelates DOTA-xPy (x = 1-4) that sequentially substitute carboxyl moieties with pyridyl moieties on a DOTA backbone.

Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE.

Background: With increasing clinical demand for gallium-68, commercial germanium-68/gallium-68 ([Ge]Ge/[Ga]Ga) generators are incapable of supplying sufficient amounts of the short-lived daughter isotope. In this study, we demonstrate a high-yield, automated method for producing multi-Curie levels of [Ga]GaCl from solid zinc-68 targets and subsequent labelling to produce clinical-grade [Ga]Ga-PSMA-11 and [Ga]Ga-DOTATATE.

Results: Enriched zinc-68 targets were irradiated at up to 80 µA with 13 MeV protons for 120 min; repeatedly producing up to 194 GBq (5.

Th-Spallation-Produced Ac with Reduced Ac Content.

Recent clinical results have demonstrated remarkable treatment responses of late-stage cancer patients when treated with alpha-emitting radionuclides such as actinium-225 (Ac). The resulting intense global effort to produce greater quantities of Ac has triggered a number of emerging technologies to produce this rare, yet important, radionuclide. Accelerator-based methods for increasing global Ac production capacity have focused on the high energy (>100 MeV) proton irradiation of thorium, despite the coproduction of the undesirable Ac byproduct at 0.

Toward F-Labeled Theranostics: A Single Agent that Can Be Labeled with F, Cu, or Lu.

We report a single-molecule radiotracer that can be labeled independently with F-fluoride or radiometals ( Cu, Lu) in a single step. A prostate-specific membrane antigen (PSMA)-targeting ligand, armed with both an organotrifluoroborate and a metal-chelator (DOTA), was designed to optionally afford F-, Cu- or Lu-labeled products that were injected into mice bearing prostate cancer (LNCaP) xenografts. PET/CT images and ex vivo biodistribution data show high, specific tumor uptake irrespective of which radionuclide is used, thereby demonstrating a new approach to combining, in a single molecule, F-labeling capabilities for PET imaging with radiometalation for potential imaging and therapeutic applications.

Evaluation of H2CHXdedpa, H2dedpa- and H2CHXdedpa-N,N'-propyl-2-NI ligands for (64)Cu(ii) radiopharmaceuticals.

The chiral acyclic "pa" ligand (pa = picolinic acid) H2CHXdedpa (N4O2) and two NI-containing dedpa analogues (H2CHXdedpa-N,N'-propyl-2-NI, H2dedpa-N,N'-propyl-2-NI, NI = nitroimidazole) were studied as chelators for copper radiopharmaceuticals (CHX = cyclohexyl, H2dedpa = 1,2-[[carboxypyridin-2-yl]methylamino]ethane). The hexadentate ligand H2CHXdedpa was previously established as a superb system for (67/68)Ga radiochemistry. The solid state X-ray crystal structures of [Cu(CHXdedpa-N,N'-propyl-2-NI)] and [Cu(dedpa-N,N'-propyl-2-NI)] reveal the predicted hexadentate, distorted octahedral binding of the copper(ii) ion.

Production of Y-86 and other radiometals for research purposes using a solution target system.

Introduction: Diagnostic radiometals are typically obtained from cyclotrons by irradiating solid targets or from radioisotope generators. These methods have the advantage of high production yields, but require additional solid target handling infrastructure that is not readily available to many cyclotron facilities. Herein, we provide an overview of our results regarding the production of various positron-emitting radiometals using a liquid target system installed on a 13 MeV cyclotron at TRIUMF.

Cross-linked polyethylene glycol beads to separate 99mTc-pertechnetate from low-specific-activity molybdenum.

Unlabelled: We report a kit-based approach for the purification of sodium pertechnetate ((99m)TcO4 (-)) from solutions with high MoO4 (2-) content.

Methods: Cross-linked polyethylene glycol resins (ChemMatrix) were used to separate (99m)Tc and molybdenum in 4N NaOH. The resins were loaded at various flow rates and eluted with water to release (99m)Tc.

Implementation of Multi-Curie Production of (99m)Tc by Conventional Medical Cyclotrons.

Unlabelled: (99m)Tc is currently produced by an aging fleet of nuclear reactors, which require enriched uranium and generate nuclear waste. We report the development of a comprehensive solution to produce (99m)Tc in sufficient quantities to supply a large urban area using a single medical cyclotron.

Methods: A new target system was designed for (99m)Tc production.

(44g)Sc production using a water target on a 13MeV cyclotron.

Introduction: Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in development of less common isotopes. Herein, we describe the production of ⁴⁴Sc (t1/2=3.

PET imaging of apoptosis with (64)Cu-labeled streptavidin following pretargeting of phosphatidylserine with biotinylated annexin-V.

Purpose: In vivo detection of apoptosis is a diagnostic tool with potential clinical applications in cardiology and oncology. Radiolabeled annexin-V (anxV) is an ideal probe for in vivo apoptosis detection owing to its strong affinity for phosphatidylserine (PS), the molecular flag on the surface of apoptotic cells. Most clinical studies performed to visualize apoptosis have used (99m)Tc-anxV; however, its poor distribution profile often compromises image quality.