Aspects and prospects of preclinical theranostic radiopharmaceutical development.

This article provides an overview of preclinical theranostic radiopharmaceutical development, highlighting aspects of the preclinical development stages that can lead towards a clinical trial. The key stages of theranostic radiopharmaceutical development are outlined, including target selection, tracer development, radiopharmaceutical synthesis, automation and quality control, radiopharmaceutical analysis, selecting a suitable model, preclinical imaging and pharmacokinetic analysis, preclinical therapeutic analysis, dosimetry, toxicity, and preparing for clinical translation. Each stage is described and augmented with examples from the literature.

Cu production via the Zn(p,nα)Cu nuclear reaction: An untapped, cost-effective and high energy production route.

Introduction: Copper-64 (Cu, t = 12.7 h) is a positron emitter well suited for theranostic applications with beta-emitting Cu for targeted molecular imaging and radionuclide therapy. The present work aims to evaluate the radionuclidic purity and radiochemistry of Cu produced via the Zn(p,nα)Cu nuclear reaction.

Theranostic Imaging Surrogates for Targeted Alpha Therapy: Progress in Production, Purification, and Applications.

This article highlights recent developments of SPECT and PET diagnostic imaging surrogates for targeted alpha particle therapy (TAT) radiopharmaceuticals. It outlines the rationale for using imaging surrogates to improve diagnostic-scan accuracy and facilitate research, and the properties an imaging-surrogate candidate should possess. It evaluates the strengths and limitations of each potential imaging surrogate.

High-yield cyclotron production of Pb using a sealed Tl solid target.

Introduction: Pb (t = 51.9 h, 279 keV (81 %)) is a diagnostic SPECT imaging radionuclide ideally suited for theranostic applications in combination with Pb for targeted alpha particle therapy. Our objectives were to develop a high-yield solid target Pb cyclotron production route using isotopically enriched Tl target material and the Tl(p,3n)Pb reaction as an alternative to lower energy production via the Tl(p,n)Pb reaction.

Good practices for Ga radiopharmaceutical production.

Background: The radiometal gallium-68 (Ga) is increasingly used in diagnostic positron emission tomography (PET), with Ga-labeled radiopharmaceuticals developed as potential higher-resolution imaging alternatives to traditional Tc agents. In precision medicine, PET applications of Ga are widespread, with Ga radiolabeled to a variety of radiotracers that evaluate perfusion and organ function, and target specific biomarkers found on tumor lesions such as prostate-specific membrane antigen, somatostatin, fibroblast activation protein, bombesin, and melanocortin.

Main Body: These Ga radiopharmaceuticals include agents such as [Ga]Ga-macroaggregated albumin for myocardial perfusion evaluation, [Ga]Ga-PLED for assessing renal function, [Ga]Ga-t-butyl-HBED for assessing liver function, and [Ga]Ga-PSMA for tumor imaging.

Radiolanthanum: Promising theranostic radionuclides for PET, alpha, and Auger-Meitner therapy.

Lanthanum radiometals are well positioned to serve as theranostic PET radiometals for targeted radionuclide therapy. The positron emitters La and La show promise to serve as unique PET imaging agents for Ac targeted alpha-particle therapy, the Ce/La pair has PET imaging potential with both Ac and Th, and La has potential in targeted Auger-Meitner electron therapy. With easily accessible cyclotron production routes, effective and efficient chemical separations, and robust chelation chemistry, these radionuclides are well poised for additional preclinical and clinical PET and targeted radionuclide therapy studies.

First In Vivo and Phantom Imaging of Cyclotron-Produced La as a Theranostic Radionuclide for Ac and La.

Theranostic isotope pairs have gained recent clinical interest because they can be labeled to the same tracer and applied for diagnostic and therapeutic purposes. The goals of this study were to investigate cyclotron production of clinically relevant La activities using natural and isotopically enriched barium target material, compare fundamental PET phantom imaging characteristics of La with those of common PET radionuclides, and demonstrate in vivo preclinical PET tumor imaging using La-PSMA-I&T. La was produced on a 24-MeV cyclotron using an aluminum-indium sealed target with 150-200 mg of isotopically enriched BaCO, BaCO, and Ba metal.

Targeted Alpha Therapy: Progress in Radionuclide Production, Radiochemistry, and Applications.

This review outlines the accomplishments and potential developments of targeted alpha (α) particle therapy (TAT). It discusses the therapeutic advantages of the short and highly ionizing path of α-particle emissions; the ability of TAT to complement and provide superior efficacy over existing forms of radiotherapy; the physical decay properties and radiochemistry of common α-emitters, including Ac, Bi, Ra, Pb, Th, Ra, At, and Tb; the production techniques and proper handling of α-emitters in a radiopharmacy; recent preclinical developments; ongoing and completed clinical trials; and an outlook on the future of TAT.

High yield cyclotron production of a novel La theranostic pair for nuclear medicine.

This study reports the high-yield production of a novel La theranostic pair at a 22 MeV proton beam energy as an attractive alternative to the recently introduced La pair, demonstrating over an order of magnitude production increase of La (231 ± 8 MBq La and 166 ± 5 MBq La at End of Bombardment (EOB)) compared to 11.9 MeV production of La (0.82 ± 0.

Positron emission tomography imaging of the γ-aminobutyric acid system.

In this review, we summarize the recent development of positron emission tomography (PET) radioligands for γ-aminobutyric acid A (GABA) receptors and their potential to measure changes in endogenous GABA levels and highlight the clinical and translational applications of GABA-sensitive PET radioligands. We review the basic physiology of the GABA system with a focus on the importance of GABA receptors in the brain and specifically the benzodiazepine binding site. Challenges for the development of central nervous system radioligands and particularly for radioligands with increased GABA sensitivity are outlined, as well as the status of established benzodiazepine site PET radioligands and agonist GABA radioligands.

PET radioligands targeting the brain GABAA /benzodiazepine receptor complex.

The development of positron emission tomography radioligands for the GABAA /benzodiazepine receptor complex (GABAA receptor) labeled with (11) C and (18) F is examined. The review covers labeling strategies as well as brief biological evaluations of radioligands. In addition, we assess the special considerations that must be taken during a development program for radioligands targeting the GABAA receptor and explore some of the challenges that lie ahead.

Palladium mediated ¹¹C-cyanation and characterization in the non-human primate brain of the novel mGluR5 radioligand [¹¹C]AZD9272.

Introduction: The aims of the present positron emission tomography (PET) study were to set up a system for (11)C-cyanation labeling of the selective mGluR5-antagonist [(11)C]AZD9272 and to perform the first in vivo characterization of [(11)C]AZD9272 binding in cynomolgus monkeys.

Methods: [(11)C]AZD9272 was labeled using palladium mediated (11)C-cyanation. Altogether seven PET measurements were performed in three cynomolgus monkeys including baseline and co-injection experiments with unlabelled AZD9272 (0.

Synthesis and evaluation of 2-chloro N-[(S)-{(S)-1-[11 C]methylpiperidin-2-yl} (phenyl)methyl]3-trifluoromethyl-benzamide ([11 C]N-methyl-SSR504734) as a PET radioligand for glycine transporter 1.

Background: Dysfunction of the glycine transporter 1 (GlyT1) has been suggested to be involved in psychiatric disorders such as schizophrenia. GlyT1 inhibitors have therefore been considered to have antipsychotic therapeutic potential. Positron emission tomography (PET) imaging probes for GlyT1 are, consequently, expected to be useful for investigating the mechanism of such disease conditions and for measuring occupancy of GlyT1 inhibitors in vivo.

Development of a PET radioligand for the central 5-HT1B receptor: radiosynthesis and characterization in cynomolgus monkeys of eight radiolabeled compounds.

Introduction: The serotonin 1B (5-HT(1B)) receptor has been implicated in several psychiatric disorders and is a potential pharmacological target in the treatment of depression. The aim of this study was to develop a radioligand for positron emission tomography (PET) imaging of the 5-HT(1B) receptor in the primate brain in vivo.

Methods: Eight carboxamide radioligands (1-8) from three different core structures were radiolabeled with carbon-11 employing N-methylation with [(11)C]methyl triflate on the piperazine structural moiety.

Radiosynthesis of the candidate beta-amyloid radioligand [(11)C]AZD2184: Positron emission tomography examination and metabolite analysis in cynomolgus monkeys.

Beta-amyloid accumulation is associated with the pathogenesis of Alzheimer's disease (AD). AZD2184, a new radioligand for high-contrast positron emission tomography (PET) imaging of Abeta-deposits, has recently been developed and characterized in vitro and in rodents ex vivo. The objective of this study was to label AZD2184 with carbon-11, to perform in vivo characterization of [(11)C]AZD2184 ([(11)C]5) in the cynomolgus monkey brain as well as whole-body dosimetry, and to examine the metabolism of the labeled radioligand.