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Nuclear Medicine for Prediction of Therapy Efficacy and Therapeutic Evaluation in Oncology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 27164

Special Issue Editors

Prof. Françoise Kraeber-Bodéré

E-Mail Website
Guest Editor
CRCINA, INSERM, CNRS, Université d’Angers, Université de Nantes, 44093 Nantes, France; Nuclear Medicine Department, University Hospital, 44093 Nantes, France; Nuclear Medicine Department, ICO-René Gauducheau Cancer Center, 44800 Saint-Herblain, France
Interests: FDG-PET; Immuno-PET; hematology; multiple myeloma; lymphoma; theranostics; radionuclide therapy; therapeutic evaluation; radiomics
Dr. Clément Bailly

E-Mail Website
Guest Editor
1. CRCINA, INSERM, CNRS, Université d’Angers, Université de Nantes, 44093 Nantes, France
2. Nuclear Medicine Department, University Hospital, 44093 Nantes, Franc
Interests: nuclear oncology; radionuclide therapy; radioimmunotherapy; PET; theranostics; radiomics; therapeutic evaluation

Special Issue Information

Dear Colleagues,

The field of molecular imaging has been revolutionized in the last 20 years by the development of nuclear medicine and particularly positron emission tomography (PET). This non-invasive molecular imaging technique enables direct and longitudinal in vivo studies of critical molecular processes. It has undoubtedly changed the landscape of cancer management, providing a whole-body method of assessing tumor heterogeneity, through the use of multiple radiopharmaceuticals, each providing different information or through the information derived from the uptakes’ analysis of a tracer such as 18F-fluoro-deoxyglucose (FDG). This imaging technique is continually proving its ability and potential to characterize tumor status for personalized medicine, such as monitoring response to treatment or assessing tumor targeting of the drug.

This Special Issue aims to give a comprehensive overview of the role of nuclear medicine in cancer management, in providing essential information in clinical practice for treatment decision-making strategies, to better select patients with poor prognosis for more intensive therapy or those eligible for targeted therapy. This issue will highlight recent significant accomplishments of PET applications with both 18-fluorodeoxyglucose (FDG) and non-FDG tracers regarding therapeutic evaluation and prediction of therapies’ efficacy moreover outlining the challenges of current theranostic developments.

Prof. Françoise Kraeber-Bodéré
Dr. Clément Bailly
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • FDG-PET/CT
  • oncological imaging
  • therapeutic evaluation
  • solid tumors
  • lymphoma
  • myeloma
  • radiomics
  • theranostics
  • new tracers

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Published Papers (5 papers)

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Research

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16 pages, 2787 KiB  
Article
Radiolabeled 6-(2, 3-Dichlorophenyl)-N4-methylpyrimidine-2, 4-diamine (TH287): A Potential Radiotracer for Measuring and Imaging MTH1
by Huaping Chen, Sadia Afrin, Yingqiu Guo, Wenhua Chu, Tammie L.S. Benzinger, Buck E. Rogers, Joel R. Garbow, Joel S. Perlmutter, Dong Zhou and Jinbin Xu
Int. J. Mol. Sci. 2020, 21(22), 8860; https://doi.org/10.3390/ijms21228860 - 23 Nov 2020
Cited by 3 | Viewed by 2864
Abstract
MTH1 (MutT homolog 1) or NUDT1 (Nudix Hydrolase 1), also known as oxidized purine nucleoside triphosphatase, has potential as a biomarker for monitoring cancer progression and quantifying target engagement for relevant therapies. In this study, we validate one MTH1 inhibitor TH287 as a [...] Read more.
MTH1 (MutT homolog 1) or NUDT1 (Nudix Hydrolase 1), also known as oxidized purine nucleoside triphosphatase, has potential as a biomarker for monitoring cancer progression and quantifying target engagement for relevant therapies. In this study, we validate one MTH1 inhibitor TH287 as a PET MTH1 radiotracer. TH287 was radiolabeled with tritium and the binding of [3H]TH287 to MTH1 was evaluated in live glioblastoma cells (U251MG) through saturation and competitive binding assays, together with in vitro enzymatic assays. Furthermore, TH287 was radiolabeled with carbon-11 for in vivo microPET studies. Saturation binding assays show that [3H]TH287 has a dissociation constant (Kd) of 1.97 ± 0.18 nM, Bmax of 2676 ± 122 fmol/mg protein for U251MG cells, and nH of 0.98 ± 0.02. Competitive binding assays show that TH287 (Ki: 3.04 ± 0.14 nM) has a higher affinity for MTH1 in U251MG cells compared to another well studied MTH1 inhibitor: (S)-crizotinib (Ki: 153.90 ± 20.48 nM). In vitro enzymatic assays show that TH287 has an IC50 of 2.2 nM in inhibiting MTH1 hydrolase activity and a Ki of 1.3 nM from kinetics assays, these results are consistent with our radioligand binding assays. Furthermore, MicroPET imaging shows that [11C]TH287 gets into the brain with rapid clearance from the brain, kidney, and heart. The results presented here indicate that radiolabeled TH287 has favorable properties to be a useful tool for measuring MTH1 in vitro and for further evaluation for in vivo PET imaging MTH1 of brain tumors and other central nervous system disorders. Full article
(This article belongs to the Special Issue Nuclear Medicine for Prediction of Therapy Efficacy and Therapeutic Evaluation in Oncology)
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9 pages, 765 KiB  
Communication
MGMT Promoter Methylation and IDH1 Mutations Do Not Affect [18F]FDOPA Uptake in Primary Brain Tumors
by Andrea Cimini, Agostino Chiaravalloti, Maria Ricci, Veronica Villani, Gianluca Vanni and Orazio Schillaci
Int. J. Mol. Sci. 2020, 21(20), 7598; https://doi.org/10.3390/ijms21207598 - 14 Oct 2020
Cited by 7 | Viewed by 2021
Abstract
The aim of our study was to investigate the effects of methylation of O⁶-methylguanine-DNA methyltransferase promoter (MGMTp) and isocitrate dehydrogenase 1 (IDH 1) mutations on amino acid metabolism evaluated with 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine ([18F] FDOPA) positron emission tomography/computed tomography (PET/CT). Seventy-two [...] Read more.
The aim of our study was to investigate the effects of methylation of O⁶-methylguanine-DNA methyltransferase promoter (MGMTp) and isocitrate dehydrogenase 1 (IDH 1) mutations on amino acid metabolism evaluated with 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine ([18F] FDOPA) positron emission tomography/computed tomography (PET/CT). Seventy-two patients with primary brain tumors were enrolled in the study (33 women and 39 men; mean age 44 ± 12 years old). All of them were subjected to PET/CT examination after surgical treatment. Of them, 29 (40.3%) were affected by grade II glioma and 43 (59.7%) by grade III. PET/CT was scored as positive or negative and standardized uptake value ratio (SUVr) was calculated as the ratio between SUVmax of the lesion vs that of the background. Statistical analysis was performed with the Mann–Whitney U test. Methylation of MGMTp was detectable in 61 out of the 72 patients examinated. Mean SUVr in patients without methylation of MGMTp was 1.44 ± 0,38 vs. 1.35 ± 0.48 of patients with methylation (p = 0.15). Data on IDH1 mutations were available for 43 subjects; of them, 31 are IDH-mutant. Mean SUVr was 1.38 ± 0.51 in patients IDH mutant and 1.46 ± 0.56 in patients IDH wild type. MGMTp methylation and IDH1 mutations do not affect [18F] FDOPA uptake in primary brain tumors and therefore cannot be assessed or predicted by radiopharmaceutical uptake parameters. Full article
(This article belongs to the Special Issue Nuclear Medicine for Prediction of Therapy Efficacy and Therapeutic Evaluation in Oncology)
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Review

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26 pages, 5448 KiB  
Review
PET Molecular Imaging: A Holistic Review of Current Practice and Emerging Perspectives for Diagnosis, Therapeutic Evaluation and Prognosis in Clinical Oncology
by Valentin Duclos, Alex Iep, Léa Gomez, Lucas Goldfarb and Florent L. Besson
Int. J. Mol. Sci. 2021, 22(8), 4159; https://doi.org/10.3390/ijms22084159 - 16 Apr 2021
Cited by 43 | Viewed by 7033
Abstract
PET/CT molecular imaging has been imposed in clinical oncological practice over the past 20 years, driven by its two well-grounded foundations: quantification and radiolabeled molecular probe vectorization. From basic visual interpretation to more sophisticated full kinetic modeling, PET technology provides a unique opportunity [...] Read more.
PET/CT molecular imaging has been imposed in clinical oncological practice over the past 20 years, driven by its two well-grounded foundations: quantification and radiolabeled molecular probe vectorization. From basic visual interpretation to more sophisticated full kinetic modeling, PET technology provides a unique opportunity to characterize various biological processes with different levels of analysis. In clinical practice, many efforts have been made during the last two decades to standardize image analyses at the international level, but advanced metrics are still under use in practice. In parallel, the integration of PET imaging with radionuclide therapy, also known as radiolabeled theranostics, has paved the way towards highly sensitive radionuclide-based precision medicine, with major breakthroughs emerging in neuroendocrine tumors and prostate cancer. PET imaging of tumor immunity and beyond is also emerging, emphasizing the unique capabilities of PET molecular imaging to constantly adapt to emerging oncological challenges. However, these new horizons face the growing complexity of multidimensional data. In the era of precision medicine, statistical and computer sciences are currently revolutionizing image-based decision making, paving the way for more holistic cancer molecular imaging analyses at the whole-body level. Full article
(This article belongs to the Special Issue Nuclear Medicine for Prediction of Therapy Efficacy and Therapeutic Evaluation in Oncology)
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14 pages, 3230 KiB  
Review
Functional Imaging for Therapeutic Assessment and Minimal Residual Disease Detection in Multiple Myeloma
by Bastien Jamet, Elena Zamagni, Cristina Nanni, Clément Bailly, Thomas Carlier, Cyrille Touzeau, Anne-Victoire Michaud, Philippe Moreau, Caroline Bodet-Milin and Françoise Kraeber-Bodere
Int. J. Mol. Sci. 2020, 21(15), 5406; https://doi.org/10.3390/ijms21155406 - 29 Jul 2020
Cited by 14 | Viewed by 3253
Abstract
Serum markers and bone marrow examination are commonly used for monitoring therapy response in multiple myeloma (MM), but this fails to identify minimal residual disease (MRD), which frequently persists after therapy even in complete response patients, and extra-medullary disease escape. Positron emission tomography [...] Read more.
Serum markers and bone marrow examination are commonly used for monitoring therapy response in multiple myeloma (MM), but this fails to identify minimal residual disease (MRD), which frequently persists after therapy even in complete response patients, and extra-medullary disease escape. Positron emission tomography with computed tomography using 18F-deoxyglucose (FDG-PET/CT) is the reference imaging technique for therapeutic assessment and MRD detection in MM. To date, all large prospective cohort studies of transplant-eligible newly diagnosed MM patients have shown a strong and independent pejorative prognostic impact of not obtaining complete metabolic response by FDG-PET/CT after therapy, especially before maintenance. The FDG-PET/CT and MRD (evaluated by flow cytometry or next-generation sequencing at 10−5 and 10−6 levels, respectively) results are complementary for MRD detection outside and inside the bone marrow. For patients with at least a complete response, to reach double negativity (FDG-PET/CT and MRD) is a predictive surrogate for patient outcome. Homogenization of FDG-PET/CT interpretation after therapy, especially clarification of complete metabolic response definition, is currently underway. FDG-PET/CT does not allow MRD to be evaluated when it is negative at initial workup of symptomatic MM. New PET tracers such as CXCR4 ligands have shown high diagnostic value and could replace FDG in this setting. New sensitive functional magnetic resonance imaging (MRI) techniques such as diffusion-weighted MRI appear to be complementary to FDG-PET/CT for imaging MRD detection. The goal of this review is to examine the feasibility of functional imaging, especially FDG-PET/CT, for therapeutic assessment and MRD detection in MM. Full article
(This article belongs to the Special Issue Nuclear Medicine for Prediction of Therapy Efficacy and Therapeutic Evaluation in Oncology)
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18 pages, 1009 KiB  
Review
Current Perspectives on 89Zr-PET Imaging
by Joon-Kee Yoon, Bok-Nam Park, Eun-Kyoung Ryu, Young-Sil An and Su-Jin Lee
Int. J. Mol. Sci. 2020, 21(12), 4309; https://doi.org/10.3390/ijms21124309 - 17 Jun 2020
Cited by 91 | Viewed by 11288
Abstract
89Zr is an emerging radionuclide that plays an essential role in immuno-positron emission tomography (PET) imaging. The long half-life of 89Zr (t1/2 = 3.3 days) is favorable for evaluating the in vivo distribution of monoclonal antibodies. Thus, the use of [...] Read more.
89Zr is an emerging radionuclide that plays an essential role in immuno-positron emission tomography (PET) imaging. The long half-life of 89Zr (t1/2 = 3.3 days) is favorable for evaluating the in vivo distribution of monoclonal antibodies. Thus, the use of 89Zr is promising for monitoring antibody-based cancer therapies. Immuno-PET combines the sensitivity of PET with the specificity of antibodies. A number of studies have been conducted to investigate the feasibility of 89Zr immuno-PET imaging for predicting the efficacy of radioimmunotherapy and antibody therapies, imaging target expression, detecting target-expressing tumors, and the monitoring of anti-cancer chemotherapies. In this review, we summarize the current status of PET imaging using 89Zr in both preclinical and clinical studies by highlighting the use of immuno-PET for the targets of high clinical relevance. We also present 89Zr-PET applications other than immuno-PET, such as nanoparticle imaging and cell tracking. Finally, we discuss the limitations and the ongoing research being performed to overcome the remaining hurdles. Full article
(This article belongs to the Special Issue Nuclear Medicine for Prediction of Therapy Efficacy and Therapeutic Evaluation in Oncology)
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