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Establishing Radiolanthanum Chemistry for Targeted Nuclear Medicine Applications.

ABSTRACT: We report the first targeted nuclear medicine application of the lanthanum radionuclides ^132/135 La. These isotopes represent a matched pair for diagnosis via the positron emissions of ¹³² La and therapy mediated by the Auger electron emissions of ¹³⁵ La. We identify two effective chelators, known as DO3Apic and macropa, for these radionuclides. The 18-membered macrocycle, macropa, bound ^132/135 La with better molar activity than DO3Apic under similar conditions. These chelators were conjugated to the prostate-specific membrane antigen (PSMA)-targeting agent DUPA to assess the use of radiolanthanum for in vivo imaging. The ^132/135 La-labeled targeted constructs showed high uptake in tumor xenografts expressing PSMA. This study validates the use of these radioactive lanthanum isotopes for imaging applications and motivates future work to assess the therapeutic effects of the Auger electron emissions of ¹³⁵ La.

SUBMITTER: Aluicio-Sarduy E

PROVIDER: S-EPMC7261199 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Establishing Radiolanthanum Chemistry for Targeted Nuclear Medicine Applications.

Aluicio-Sarduy Eduardo E Thiele Nikki A NA Martin Kirsten E KE Vaughn Brett A BA Devaraj Justin J Olson Aeli P AP Barnhart Todd E TE Wilson Justin J JJ Boros Eszter E Engle Jonathan W JW

Chemistry (Weinheim an der Bergstrasse, Germany) 20200109 6

We report the first targeted nuclear medicine application of the lanthanum radionuclides 132/135 La. These isotopes represent a matched pair for diagnosis via the positron emissions of 132 La and therapy mediated by the Auger electron emissions of 135 La. We identify two effective chelators, known as DO3Apic and macropa, for these radionuclides. The 18-membered macrocycle, macropa, bound 132/135 La with better molar activity than DO3Apic under similar ...[more]

PMID: 31743504

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Project description:Immunotherapy by using immune checkpoint inhibitors is a revolutionary development in oncology. Medical imaging is also impacted by this new therapy, particularly nuclear medicine imaging (also called radionuclide imaging), which uses radioactive tracers to visualize metabolic functions. Our aim was to review the current applications of nuclear medicine imaging in immunotherapy, along with their limitations, and the perspectives offered by this imaging modality. Method: Articles describing the use of radionuclide imaging in immunotherapy were researched using PubMed by April 2019 and analyzed. Results: More than 5000 articles were analyzed, and nearly 100 of them were retained. Radionuclide imaging, notably 18F-FDG PET/CT, already has a major role in many cancers for pre-therapeutic and therapeutic evaluation, diagnoses of adverse effects, called immune-related adverse events (IrAE), and end-of-treatment evaluations. However, these current applications can be hindered by immunotherapy, notably due to atypical response patterns such as pseudoprogression, which is defined as an increase in the size of lesions, or the visualization of new lesions, followed by a response, and hyperprogression, which is an accelerated tumor growth rate after starting treatment. To overcome these difficulties, new opportunities are offered, particularly therapeutic evaluation criteria adapted to immunotherapy and immuno-PET allowing us to predict responses to immunotherapy. Moreover, some new technological solutions are also promising, such as radiomic analyses and body composition on associated anatomical images. However, more research has to be done, notably for the diagnosis of hyperprogression and pseudoprogression. Conclusion: Immunotherapy, by its major impact on cancer and by the new patterns generated on images, is revolutionary in the field of medical images. Nuclear medicine imaging is already established and will be able to help meet new challenges through its plasticity.

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Establishing Radiolanthanum Chemistry for Targeted Nuclear Medicine Applications.

Publications

Establishing Radiolanthanum Chemistry for Targeted Nuclear Medicine Applications.

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