Development of Novel Radiotracers for PET Imaging

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

Deadline for manuscript submissions: 30 June 2024 | Viewed by 2199

Special Issue Editors

School of Pharmaceutical Sciences, Nanjing Tech University, No. 30 South Puzhu Road, Nanjing 211816, China
Interests: HTS library design; H2L medchem; infectious and neglected diseases; epigenetic modifiers; and peptidomimetic design and synthesis
Special Issues, Collections and Topics in MDPI journals
School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA
Interests: medicinal chemistry; kinase inhibitors; PET radioligand development; neuroimaging

Special Issue Information

Dear Colleagues,

PET (positron emission tomography) is a medical imaging technique that uses a radioactive tracer to visualize metabolic and physiological processes in the body. Some of the common applications of PET imaging include: cancer detection and staging, monitoring neurological disorders (Alzheimer's disease, Parkinson's disease, and epilepsy), cardiac imaging, infectious disease (tuberculosis, HIV, and hepatitis), psychiatric disorders (depression, anxiety, and schizophrenia) and molecular imaging. PET imaging can be used to visualize specific molecules in the body, such as neurotransmitters, receptors, and enzymes. This can help researchers better understand the mechanisms of disease and develop new therapies. Overall, PET imaging is a powerful tool for visualizing metabolic and physiological processes in the body and has many important clinical and research applications.

The development of new radiotracers involves a multidisciplinary approach that combines chemistry, biology, pharmacology, and imaging sciences. The process begins with the selection of a target molecule or biological process of interest, followed by the design and synthesis of a suitable radiotracer. The radiotracer is then evaluated in vitro and in vivo for its pharmacokinetic properties, specificity, and sensitivity.

Some of the challenges in developing new radiotracers include the short half-life of some isotopes, such as carbon-11 and fluorine-18, which require on-site cyclotron facilities for their production. Additionally, the radiotracer should have a high selectivity and affinity for the target molecule or biological process of interest while also minimizing off-target binding and nonspecific uptake. The radiotracer should also have favorable pharmacokinetic properties, such as rapid clearance from non-target tissues and minimal toxicity.

There are several approaches to developing new radiotracers, including the use of small molecules, peptides, antibodies, and nanoparticles. Small molecules are often preferred for their ease of synthesis and favorable pharmacokinetics. Peptides and antibodies offer a high selectivity and specificity, but their larger size can lead to a slower clearance and potential immunogenicity. Nanoparticles have unique properties, such as a high surface area, targeting capability, and drug-loading capacity, but their large size can also lead to a slower clearance and potential toxicity.

Overall, the development of novel radiotracers for PET imaging is a challenging yet critical area of research with tremendous potential for advancing our understanding of various biological processes and improving the diagnosis and treatment of diseases.

This Special Issue entitled “Development of Novel Radiotracers for PET Imaging” aims to focus on the state of the art in the field of cancer and other neurological applications. You are cordially invited to contribute to this Special Issue with original articles as well as reviews.

Prof. Dr. Jonathan B. Baell
Dr. Ramesh Mudududdla
Guest Editors

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Keywords

  • radiopharmaceuticals
  • molecular imaging
  • positron emission tomography (PET)
  • single photon emission computed tomography (SPECT)
  • oncology
  • neurological disorders

Published Papers (2 papers)

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Research

23 pages, 5607 KiB  
Article
Head-to-Head Comparison of SSTR Antagonist [68Ga]Ga-DATA5m-LM4 with SSTR Agonist [68Ga]Ga-DOTANOC PET/CT in Patients with Well Differentiated Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Imaging Study
by Rahul Viswanathan, Sanjana Ballal, Madhav P. Yadav, Frank Roesch, Parvind Sheokand, Swayamjeet Satapathy, Madhavi Tripathi, Shipra Agarwal, Euy Sung Moon and Chandrasekhar Bal
Pharmaceuticals 2024, 17(3), 275; https://doi.org/10.3390/ph17030275 - 22 Feb 2024
Viewed by 1019
Abstract
Neuroendocrine tumors (NETs) are slow-growing tumors that express high levels of somatostatin receptors (SSTRs). Recent studies have shown the superiority of radiolabeled SSTR antagonists in theranostics compared to agonists. In this prospective study, we compared the diagnostic efficacy between [68Ga]Ga-DOTANOC and [...] Read more.
Neuroendocrine tumors (NETs) are slow-growing tumors that express high levels of somatostatin receptors (SSTRs). Recent studies have shown the superiority of radiolabeled SSTR antagonists in theranostics compared to agonists. In this prospective study, we compared the diagnostic efficacy between [68Ga]Ga-DOTANOC and [68Ga]Ga-DATA5m-LM4 in the detection of primary and metastatic lesions in patients with well differentiated gastroenteropancreatic (GEP) NETs. Histologically proven GEP-NET patients underwent [68Ga]Ga-DOTANOC & [68Ga]Ga-DATA5m-LM4 PET/CT scans, which were analyzed. The qualitative analysis involved the visual judgment of radiotracer uptake validated by the morphological findings using CT, which was considered as the reference standard. Quantitative comparisons were presented as the standardized uptake value (SUV) corrected for lean body mass: SULpeak, SULavg, and tumor-to-background ratios (TBR). In total, 490 lesions were confirmed via diagnostic CT. The lesion-based sensitivity of [68Ga]Ga-DATA5m-LM4 PET/CT was 94.28% (462/490) and 83.46% (409/490) for [68Ga]Ga-DOTANOC PET/CT (p < 0.0001). [68Ga]Ga-DATA5m-LM4 had statistical significance over [68Ga]Ga-DOTANOC in liver metastases [100% vs. 89.4%; p < 0.0001 (292 vs. 253 {283 lesions on CT})] and bone metastases [100% vs. 82.9%; p = 0.005 (45 vs. 34 {41 lesions on CT})]. Statistical significance was also noted for the TBR SULpeak of the primary and liver lesions. [68Ga]Ga-DATA5m-LM4 showed better sensitivity and a higher target-to-background ratio than [68Ga]Ga-DOTANOC PET/CT. [68Ga]Ga-DATA5m-LM4 PET/CT can be used to quantify the extent of skeletal and liver metastases for better planning of SSTR agonist- or antagonist-based therapy. Full article
(This article belongs to the Special Issue Development of Novel Radiotracers for PET Imaging)
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14 pages, 2133 KiB  
Article
Development and Preclinical Evaluation of [68Ga]BMSH as a New Potent Positron Emission Tomography Tracer for Imaging Programmed Death-Ligand 1 Expression
by Yong Huang, Chengze Li, Zhongjing Li, Qiong Wang, Size Huang, Qi Liu and Ying Liang
Pharmaceuticals 2023, 16(10), 1487; https://doi.org/10.3390/ph16101487 - 19 Oct 2023
Cited by 1 | Viewed by 879
Abstract
Immunotherapy targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) pathway has shown remarkable efficacy against various cancers, but the overall response rate (ORR) is still low. PD-L1 expression in tumors may predict treatment response to immunotherapy. Indeed, ongoing clinical studies [...] Read more.
Immunotherapy targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) pathway has shown remarkable efficacy against various cancers, but the overall response rate (ORR) is still low. PD-L1 expression in tumors may predict treatment response to immunotherapy. Indeed, ongoing clinical studies utilize a few PD-L1 radiotracers to assess PD-L1 expression as a predictive biomarker for immunotherapy. Here, we present a novel positron emission tomography (PET) radiotracer called [68Ga]BMSH, which is derived from a small molecule inhibitor specifically targeting the binding site of PD-L1. The inhibitor was modified to optimize its in vivo pharmacokinetic properties and enable chelation of 68Ga. In vitro evaluation revealed [68Ga]BMSH possessed a strong binding affinity, high specificity, and rapid internalization in PD-L1 overexpressing cells. Biodistribution studies showed that PD-L1 overexpressing tumors had an uptake of [68Ga]BMSH at 4.22 ± 0.65%ID/g in mice, while the number was 2.23 ± 0.41%ID/g in PD-L1 low-expressing tumors. Micro-PET/CT imaging of tumor-bearing mice further confirmed that, compared to [18F]FDG, [68Ga]BMSH can specifically identify tumors with varying levels of PD-L1 expression. Our findings suggest that the [68Ga]BMSH is a PD-L1 radioligand with ideal imaging properties, and its further application in the clinical screening of PD-L1 overexpressing tumors may improve ORR for immunotherapy. Full article
(This article belongs to the Special Issue Development of Novel Radiotracers for PET Imaging)
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