Recent Developments of Nuclear Medicine in Cancer Diagnosis and Theranostics

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (18 November 2022) | Viewed by 25419

Special Issue Editor


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Guest Editor
1. Department of Nuclear Medicine, Humanitas University and Clinical and Research Center, Rozzano, 20089, Milan, Italy;
2. Department of Radiology and Nuclear Medicine, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands
3. Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box 9101, Nijmegen, 6500 HB, Netherlands
Interests: oncology; cancer imaging; molecular imaging; hybrid imaging; PET/CT; theranostics

Special Issue Information

Dear Colleagues,

In recent years, advances in nuclear medicine diagnostics and theranostics have entered into clinical practice. The development of a large number of novel molecules in basic science and early clinical trials hold promise for a continued growth of nuclear medicine’s contribution to clinical oncology, using the unique characteristics of targeted small molecules and constructs derived from antibodies with high affinity for tumor cells and the tumor microenvironment. Exploiting the unique feature of nuclear medicine to depict and quantify the pharmacokinetics, pharmacodynamics, and dynamic distribution of radiopharmaceuticals in tumors and organs, theranostics is a true exponent of precision medicine. The concept of theranostics is at the very basis of nuclear medicine, as exemplified by the very effective treatment of thyroid cancer patients with radioisotopes of iodine for more than 75 years. More recently, radiolabeled somatostatin analogues have been approved as therapeutics for neuroendocrine tumors, soon to be followed by radiolabeled PSMA for diagnosis and treatment of prostate cancer. Many more radioactive drugs are in the pipeline and will hopefully advance in the near future. Being a truly multidisciplinary profession, drug development in nuclear medicine requires the interplay of physicians, radiochemists, physicists, and radiopharmacists. This Special Issue of Cancers will highlight the state-of-the-art in nuclear medicine diagnosis and therapy and provide an insight into new developments at the verge of clinical application.

Prof. Dr. Wim J.G. Oyen
Guest Editor

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Keywords

  • nuclear medicine
  • cancer imaging
  • molecular imaging
  • hybrid imaging
  • theranostics
  • radioligand therapy
  • receptor-targeted systemic radiotherapy

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Published Papers (5 papers)

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Research

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15 pages, 10239 KiB  
Article
Anti-Tumor Efficacy of PD-L1 Targeted Alpha-Particle Therapy in a Human Melanoma Xenograft Model
by Marisa Capitao, Justine Perrin, Sylvain Simon, Sébastien Gouard, Nicolas Chouin, Frank Bruchertseifer, Alfred Morgenstern, Latifa Rbah-Vidal, Michel Chérel, Emmanuel Scotet, Nathalie Labarrière, Yannick Guilloux and Joëlle Gaschet
Cancers 2021, 13(6), 1256; https://doi.org/10.3390/cancers13061256 - 12 Mar 2021
Cited by 7 | Viewed by 3208
Abstract
PD-L1 (programmed death-ligand 1, B7-H1, CD274), the ligand for PD-1 inhibitory receptor, is expressed on various tumors, and its expression is correlated with a poor prognosis in melanoma. Anti-PD-L1 mAbs have been developed along with anti-CTLA-4 and anti-PD-1 antibodies for immune checkpoint inhibitor [...] Read more.
PD-L1 (programmed death-ligand 1, B7-H1, CD274), the ligand for PD-1 inhibitory receptor, is expressed on various tumors, and its expression is correlated with a poor prognosis in melanoma. Anti-PD-L1 mAbs have been developed along with anti-CTLA-4 and anti-PD-1 antibodies for immune checkpoint inhibitor (ICI) therapy, and anti-PD-1 mAbs are now used as first line treatment in melanoma. However, many patients do not respond to ICI therapies, and therefore new treatment alternatives should be developed. Because of its expression on the tumor cells and on immunosuppressive cells within the tumor microenvironment, PD-L1 represents an interesting target for targeted alpha-particle therapy (TAT). We developed a TAT approach in a human melanoma xenograft model that stably expresses PD-L1 using a 213Bi-anti-human-PD-L1 mAb. Unlike treatment with unlabeled anti-human-PD-L1 mAb, TAT targeting PD-L1 significantly delayed melanoma tumor growth and improved animal survival. A slight decrease in platelets was observed, but no toxicity on red blood cells, bone marrow, liver or kidney was induced. Anti-tumor efficacy was associated with specific tumor targeting since no therapeutic effect was observed in animals bearing PD-L1 negative melanoma tumors. This study demonstrates that anti-PD-L1 antibodies may be used efficiently for TAT treatment in melanoma. Full article
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Review

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23 pages, 2069 KiB  
Review
Radiolabeled Antibodies for Cancer Imaging and Therapy
by Sagun Parakh, Sze Ting Lee, Hui K. Gan and Andrew M. Scott
Cancers 2022, 14(6), 1454; https://doi.org/10.3390/cancers14061454 - 11 Mar 2022
Cited by 50 | Viewed by 7493
Abstract
Radioimmunoconjugates consist of a monoclonal antibody (mAb) linked to a radionuclide. Radioimmunoconjugates as theranostics tools have been in development with success, particularly in hematological malignancies, leading to approval by the US Food and Drug Administration (FDA) for the treatment of non-Hodgkin’s lymphoma. Radioimmunotherapy [...] Read more.
Radioimmunoconjugates consist of a monoclonal antibody (mAb) linked to a radionuclide. Radioimmunoconjugates as theranostics tools have been in development with success, particularly in hematological malignancies, leading to approval by the US Food and Drug Administration (FDA) for the treatment of non-Hodgkin’s lymphoma. Radioimmunotherapy (RIT) allows for reduced toxicity compared to conventional radiation therapy and enhances the efficacy of mAbs. In addition, using radiolabeled mAbs with imaging methods provides critical information on the pharmacokinetics and pharmacodynamics of therapeutic agents with direct relevance to the optimization of the dose and dosing schedule, real-time antigen quantitation, antigen heterogeneity, and dynamic antigen changes. All of these parameters are critical in predicting treatment responses and identifying patients who are most likely to benefit from treatment. Historically, RITs have been less effective in solid tumors; however, several strategies are being investigated to improve their therapeutic index, including targeting patients with minimal disease burden; using pre-targeting strategies, newer radionuclides, and improved labeling techniques; and using combined modalities and locoregional application. This review provides an overview of the radiolabeled intact antibodies currently in clinical use and those in development. Full article
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22 pages, 6628 KiB  
Review
Molecular Imaging and Theragnostics of Thyroid Cancers
by Luca Giovanella, Desiree’ Deandreis, Alexis Vrachimis, Alfredo Campenni and Petra Petranovic Ovcaricek
Cancers 2022, 14(5), 1272; https://doi.org/10.3390/cancers14051272 - 1 Mar 2022
Cited by 26 | Viewed by 4442
Abstract
Molecular imaging plays an important role in the evaluation and management of different thyroid cancer histotypes. The existing risk stratification models can be refined, by incorporation of tumor-specific molecular markers that have theranostic power, to optimize patient-specific (individualized) treatment decisions. Molecular imaging with [...] Read more.
Molecular imaging plays an important role in the evaluation and management of different thyroid cancer histotypes. The existing risk stratification models can be refined, by incorporation of tumor-specific molecular markers that have theranostic power, to optimize patient-specific (individualized) treatment decisions. Molecular imaging with varying radioisotopes of iodine (i.e., 131I, 123I, 124I) is an indispensable component of dynamic and theragnostic risk stratification of differentiated carcinoma (DTC) while [18F]F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) helps in addressing disease aggressiveness, detects distant metastases, and risk-stratifies patients with radioiodine-refractory DTC, poorly differentiated and anaplastic thyroid cancers. For medullary thyroid cancer (MTC), a neuroendocrine tumor derived from thyroid C-cells, [18F]F-dihydroxyphenylalanine (6-[18F]FDOPA) PET/CT and/or [18F]FDG PET/CT can be used dependent on serum markers levels and kinetics. In addition to radioiodine therapy for DTC, some theragnostic approaches are promising for metastatic MTC as well. Moreover, new redifferentiation strategies are now available to restore uptake in radioiodine-refractory DTC while new theragnostic approaches showed promising preliminary results for advanced and aggressive forms of follicular-cell derived thyroid cancers (i.e., peptide receptor radiotherapy). In order to help clinicians put the role of molecular imaging into perspective, the appropriate role and emerging opportunities for molecular imaging and theragnostics in thyroid cancer are discussed in our present review. Full article
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15 pages, 4334 KiB  
Review
Targeting PSMA Revolutionizes the Role of Nuclear Medicine in Diagnosis and Treatment of Prostate Cancer
by Wietske I. Luining, Matthijs C. F. Cysouw, Dennie Meijer, N. Harry Hendrikse, Ronald Boellaard, André N. Vis and Daniela E. Oprea-Lager
Cancers 2022, 14(5), 1169; https://doi.org/10.3390/cancers14051169 - 24 Feb 2022
Cited by 22 | Viewed by 4323
Abstract
Targeting the prostate-specific membrane antigen (PSMA) protein has become of great clinical value in prostate cancer (PCa) care. PSMA positron emission tomography/computed tomography (PET/CT) is increasingly used in initial staging and restaging at biochemical recurrence in patients with PCa, where it has shown [...] Read more.
Targeting the prostate-specific membrane antigen (PSMA) protein has become of great clinical value in prostate cancer (PCa) care. PSMA positron emission tomography/computed tomography (PET/CT) is increasingly used in initial staging and restaging at biochemical recurrence in patients with PCa, where it has shown superior detection rates compared to previous imaging modalities. Apart from targeting PSMA for diagnostic purposes, there is a growing interest in developing ligands to target the PSMA-protein for radioligand therapy (RLT). PSMA-based RLT is a novel treatment that couples a PSMA-antibody to (alpha or beta-emitting) radionuclide, such as Lutetium-177 (177Lu), to deliver high radiation doses to tumor cells locally. Treatment with 177Lu-PSMA RLT has demonstrated a superior overall survival rate within randomized clinical trials as compared to routine clinical care in patients with metastatic castration-resistant prostate cancer (mCRPC). The current review provides an overview of the literature regarding recent developments in nuclear medicine related to PSMA-targeted PET imaging and Theranostics. Full article
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29 pages, 757 KiB  
Review
Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors
by Valentina Ambrosini, Lucia Zanoni, Angelina Filice, Giuseppe Lamberti, Giulia Argalia, Emilia Fortunati, Davide Campana, Annibale Versari and Stefano Fanti
Cancers 2022, 14(4), 1055; https://doi.org/10.3390/cancers14041055 - 19 Feb 2022
Cited by 16 | Viewed by 4315
Abstract
Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors that require multidisciplinary discussion for optimal care. The theranostic approach (DOTA peptides labelled with 68Ga for diagnosis and with 90Y or 177Lu for therapy) plays a crucial role in the management of [...] Read more.
Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors that require multidisciplinary discussion for optimal care. The theranostic approach (DOTA peptides labelled with 68Ga for diagnosis and with 90Y or 177Lu for therapy) plays a crucial role in the management of NENs to assess disease extension and as a criteria for peptide receptor radionuclide therapy (PRRT) eligibility based on somatostatin receptor (SSTR) expression. On the diagnostic side, [68Ga]Ga-DOTA peptides PET/CT (SSTR PET/CT) is the gold standard for imaging well-differentiated SSTR-expressing neuroendocrine tumors (NETs). [18F]FDG PET/CT is useful in higher grade NENs (NET G2 with Ki-67 > 10% and NET G3; NEC) for more accurate disease characterization and prognostication. Promising emerging radiopharmaceuticals include somatostatin analogues labelled with 18F (to overcome the limits imposed by 68Ga), and SSTR antagonists (for both diagnosis and therapy). On the therapeutic side, the evidence gathered over the past two decades indicates that PRRT is to be considered as an effective and safe treatment option for SSTR-expressing NETs, and is currently included in the therapeutic algorithms of the main scientific societies. The positioning of PRRT in the treatment sequence, as well as treatment personalization (e.g., tailored dosimetry, re-treatment, selection criteria, and combination with other alternative treatment options), is warranted in order to improve its efficacy while reducing toxicity. Although very preliminary (being mostly hampered by lack of methodological standardization, especially regarding feature selection/extraction) and often including small patient cohorts, radiomic studies in NETs are also presented. To date, the implementation of radiomics in clinical practice is still unclear. The purpose of this review is to offer an overview of radiolabeled SSTR analogues for theranostic use in NENs. Full article
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