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.

A Theranostic Approach to Imaging and Treating Melanoma with Pb/Pb-Labeled Antibody Targeting Melanin.

Metastatic melanoma is a deadly disease that claims thousands of lives each year despite the introduction of several immunotherapeutic agents into the clinic over the past decade, inspiring the development of novel therapeutics and the exploration of combination therapies. Our investigations target melanin pigment with melanin-specific radiolabeled antibodies as a strategy to treat metastatic melanoma. In this study, a theranostic approach was applied by first labeling a chimeric antibody targeting melanin, c8C3, with the SPECT radionuclide Pb for microSPECT/CT imaging of C57Bl6 mice bearing B16-F10 melanoma tumors.

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.

Taking cyclotron Ga production to the next level: Expeditious solid target production of Ga for preparation of radiotracers.

Introduction: Gallium-68 is an important radionuclide for positron emission tomography (PET) with steadily increasing applications of Ga-based radiopharmaceuticals for clinical use. Current Ga sources are primarily Ge/Ga-generators, along with successful attempts of Ga production using a cyclotron. This study evaluated cyclotron Ga production and automated separation using expeditiously manufactured solid targets, demonstrates an order of magnitude improvement in yield compared to Ge/Ga generators, and presents a convenient alternative to existing cyclotron production processes.