Recent Advancements in Radiochemistry and PET Radiotracer Development

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Radiopharmaceutical Sciences".

Deadline for manuscript submissions: 25 August 2024 | Viewed by 4633

Special Issue Editors


E-Mail Website1 Website2
Guest Editor
1. PET Science Centre, Precision Medicine and Biosamples, Oncology R&D, AstraZeneca, Karolinska Institutet, SE-17176 Stockholm, Sweden
2. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet and Stockholm County Council, SE-17176 Stockholm, Sweden
Interests: PET; radiochemistry; automation; radioligand; drug discovery

E-Mail Website
Guest Editor
Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County Council, 17164 Stockholm, Sweden
Interests: PET; radioligand; neuroscience

Special Issue Information

Dear Colleagues,

Positron Emission Tomography (PET) is a valuable imaging technique used in various applications, including clinical diagnosis, drug discovery, and neuroscience research. PET relies upon the administration of a chemical probe, also known as radiotracers, that is labelled with a short-lived positron-emitting radionuclide (e.g., 11C, 18F, 68Ga, and 89Zr). The development of novel radiotracers requires multiple considerations, and aspects like radionuclide selection, labeling position, metabolic stability, precursor synthesis, radiolabeling procedure, automation, quality control, and regulatory aspects have to be considered.

This Special Issue aims to highlight the latest research on PET radiotracer synthesis and development, and we invite both original research and review articles on the following topics: (1) new radiolabeling strategies and isotopes for radiotracer production; (2) automation and clinical validation; (3) design and synthesis of novel PET radiotracers targeting specific biological processes, e.g., receptors, enzymes, and transporters; (4) strategies to enhance image quality and quantification; and (5) clinical translation and application of novel PET radiotracers.

Overall, this Special Issue will provide an authoritative and up-to-date resource for researchers, clinicians, and industry professionals seeking to advance PET imaging and its applications in healthcare and biomedical research.

Dr. Kenneth Dahl
Dr. Sangram Nag
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • radiochemistry
  • labeling
  • automation
  • GMP
  • PET
  • radiotracer
  • radioligand
  • radiopharmaceutical
  • drug discovery

Published Papers (5 papers)

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Research

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16 pages, 3108 KiB  
Article
Design and Construction of a Radiochemistry Laboratory and cGMP-Compliant Radiopharmacy Facility
by Angela Asor, Abdullah Metebi, Kylie Smith, Kurt Last, Elaine Strauss and Jinda Fan
Pharmaceuticals 2024, 17(6), 680; https://0-doi-org.brum.beds.ac.uk/10.3390/ph17060680 - 25 May 2024
Viewed by 540
Abstract
The establishment of a compliant radiopharmacy facility within a university setting is crucial for supporting fundamental and preclinical studies, as well as for the production of high-quality radiopharmaceuticals for clinical testing in human protocols as part of Investigational New Drug (IND) applications that [...] Read more.
The establishment of a compliant radiopharmacy facility within a university setting is crucial for supporting fundamental and preclinical studies, as well as for the production of high-quality radiopharmaceuticals for clinical testing in human protocols as part of Investigational New Drug (IND) applications that are reviewed and approved by the U.S. Food and Drug Administration (FDA). This manuscript details the design and construction of a 550 ft2 facility, which included a radiopharmacy and a radiochemistry laboratory, to support radiopharmaceutical development research and facilitate translational research projects. The facility was designed to meet FDA guidelines for the production of aseptic radiopharmaceuticals in accordance with current good manufacturing practice (cGMP). A modular hard-panel cleanroom was constructed to meet manufacturing classifications set by the International Organization of Standardization (ISO), complete with a gowning room and an anteroom. Two lead-shielded hot cells and two dual-mini hot cells, connected via underground trenches containing shielded conduits, were installed to optimize radioactive material transfer while minimizing personnel radiation exposure. Concrete blocks and lead bricks provided sufficient and cost-effective radiation shielding for the trenches. Air quality was controlled using pre-filters and high-efficiency particulate air (HEPA) filters to meet cleanroom ISO7 (Class 10,000) standards. A laminar-flow biosafety cabinet was installed in the cleanroom for preparation of sterile dose vials. Noteworthy was a laminar-flow insert in the hot cell that provided a shielded laminar-flow sterile environment meeting ISO5 (class 100) standards. The design included the constant control and monitoring of differential air pressures across the cleanroom, anteroom, gowning room, and controlled research space, as well as maintenance of temperature and humidity. The facility was equipped with state-of-the-art equipment for quality control and release testing of radiopharmaceuticals. Administrative controls and standard operating procedures (SOPs) were established to ensure compliance with manufacturing standards and regulatory requirements. Overall, the design and construction of this radiopharmacy facility exemplified a commitment to advancing fundamental, translational, and clinical applications of radiopharmaceutical research within an academic environment. Full article
(This article belongs to the Special Issue Recent Advancements in Radiochemistry and PET Radiotracer Development)
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10 pages, 4748 KiB  
Communication
Long-Term Tumor-Targeting Effect of E. coli as a Drug Delivery System
by Gun Gyun Kim, Hongje Lee, Dan Bi Jeong, Sang Wook Kim and Jae-Seon So
Pharmaceuticals 2024, 17(4), 421; https://0-doi-org.brum.beds.ac.uk/10.3390/ph17040421 - 26 Mar 2024
Viewed by 756
Abstract
To overcome the limitations of current nano/micro-scale drug delivery systems, an Escherichia coli (E. coli)-based drug delivery system could be a potential alternative, and an effective tumor-targeting delivery system can be developed by attempting to perform chemical binding to the primary [...] Read more.
To overcome the limitations of current nano/micro-scale drug delivery systems, an Escherichia coli (E. coli)-based drug delivery system could be a potential alternative, and an effective tumor-targeting delivery system can be developed by attempting to perform chemical binding to the primary amine group of a cell membrane protein. In addition, positron emission tomography (PET) is a representative non-invasive imaging technology and is actively used in the field of drug delivery along with radioisotopes capable of long-term tracking, such as zirconium-89 (89Zr). The membrane proteins were labeled with 89Zr using chelate (DFO), and not only was the long-term biodistribution in tumors and major organs evaluated in the body, but the labeling stability of 89Zr conjugated to the membrane proteins was also evaluated through continuous tracking. E. coli accumulated at high levels in the tumor within 5 min (initial time) after tail intravenous injection, and when observed after 6 days, 89Zr-DFO on the surface of E. coli was found to be stable for a long period of time in the body. In this study, we demonstrated the long-term biodistribution and tumor-targeting effect of an E. coli-based drug delivery system and verified the in vivo stability of radioisotopes labeled on the surface of E. coli. Full article
(This article belongs to the Special Issue Recent Advancements in Radiochemistry and PET Radiotracer Development)
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10 pages, 1587 KiB  
Article
A Fully Automated Synthesis of 14-(R,S)-[18F]fluoro-6-thia-heptadecanoic Acid ([18F]FTHA) on the Elixys Radiosynthesizer
by Usevalad Ustsinau, Lukas Nics, Marcus Hacker and Cecile Philippe
Pharmaceuticals 2024, 17(3), 318; https://0-doi-org.brum.beds.ac.uk/10.3390/ph17030318 - 29 Feb 2024
Cited by 1 | Viewed by 838
Abstract
14-(R,S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA) is a radiocompound for imaging the fatty acid circulation by positron emission tomography. A revived interest in imaging of lipid metabolism led us to a constant tracer production over three years, initially using a [...] Read more.
14-(R,S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA) is a radiocompound for imaging the fatty acid circulation by positron emission tomography. A revived interest in imaging of lipid metabolism led us to a constant tracer production over three years, initially using a conventional vessel-based synthesizer and later transitioning to the cassette-based Elixys synthesizer. On the Elixys module, the radiochemical yield of [18F]FTHA could be increased by more than two times, reaching 13.01 ± 5.63% at the end of the synthesis, while maintaining necessary quality control results. Full article
(This article belongs to the Special Issue Recent Advancements in Radiochemistry and PET Radiotracer Development)
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13 pages, 2705 KiB  
Article
Advancements in Microfluidic Cassette-Based iMiDEV™ Technology for Production of L-[11C]Methionine and [11C]Choline
by Hemantha Mallapura, Laurent Tanguy, Samin Mahfuz, Lovisa Bylund, Bengt Långström, Christer Halldin and Sangram Nag
Pharmaceuticals 2024, 17(2), 250; https://0-doi-org.brum.beds.ac.uk/10.3390/ph17020250 - 15 Feb 2024
Viewed by 1010
Abstract
Microfluidic technology is a highly efficient technique used in positron emission tomography (PET) radiochemical synthesis. This approach enables the precise control of reactant flows and reaction conditions, leading to improved yields and reduced synthesis time. The synthesis of two radiotracers, L-[11C]methionine [...] Read more.
Microfluidic technology is a highly efficient technique used in positron emission tomography (PET) radiochemical synthesis. This approach enables the precise control of reactant flows and reaction conditions, leading to improved yields and reduced synthesis time. The synthesis of two radiotracers, L-[11C]methionine and [11C]choline, was performed, using a microfluidic cassette and an iMiDEVTM module by employing a dose-on-demand approach for the synthesis process. We focused on optimizing the precursor amounts and radiosynthesis on the microfluidic cassette. L-[11C]methionine and [11C]choline were synthesized using a microreactor filled with a suitable resin for the radiochemical reaction. Trapping of the [11C]methyl iodide, its reaction, and solid-phase extraction purification were performed on a microreactor, achieving radiochemical yields of >80% for L-[11C]methionine and >60% for [11C]choline (n = 3). The total synthesis time for both the radiotracers was approximately 20 min. All quality control tests complied with the European Pharmacopeia standards. The dose-on-demand model allows for real-time adaptation to patient schedules, making it suitable for preclinical and clinical settings. Precursor optimization enhanced the cost efficiency without compromising the yield. The importance of dose-on-demand synthesis and optimized precursor utilization to produce L-[11C]methionine and [11C]choline was emphasized in this study. The results demonstrated the feasibility of dose-on-demand adaptations for clinical applications with reduced precursor quantities and high radiochemical yields. Full article
(This article belongs to the Special Issue Recent Advancements in Radiochemistry and PET Radiotracer Development)
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Review

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13 pages, 3692 KiB  
Review
Titanium-45 (45Ti) Radiochemistry and Applications in Molecular Imaging
by Shefali Saini and Suzanne E. Lapi
Pharmaceuticals 2024, 17(4), 479; https://0-doi-org.brum.beds.ac.uk/10.3390/ph17040479 - 9 Apr 2024
Viewed by 836
Abstract
Molecular imaging is an important part of modern medicine which enables the non-invasive identification and characterization of diseases. With the advancement of radiochemistry and scanner technology, nuclear medicine is providing insight into efficient treatment options for individual patients. Titanium-45 (45Ti) is [...] Read more.
Molecular imaging is an important part of modern medicine which enables the non-invasive identification and characterization of diseases. With the advancement of radiochemistry and scanner technology, nuclear medicine is providing insight into efficient treatment options for individual patients. Titanium-45 (45Ti) is a lesser-explored radionuclide that is garnering increasing interest for the development of positron emission tomography (PET) radiopharmaceuticals. This review discusses aspects of this radionuclide including production, purification, radiochemistry development, and molecular imaging studies. Full article
(This article belongs to the Special Issue Recent Advancements in Radiochemistry and PET Radiotracer Development)
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