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Cancer Molecular Imaging

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 26534

Special Issue Editor

Prof. Dr. Luca Giovanella

E-Mail Website
Guest Editor
1. Clinic for Nuclear Medicine and Molecular Imaging, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland
2. Clinic for Nuclear Medicine and Intedisciplinary Thyroid Centre, University Hospital of Zurich, 8091 Zurich, Switzerland
Interests: nuclear medicine; molecular imaging; theranostics; thyroid diseases; endocrine tumors; radiomics; predictive imaging; molecular biomarkers; integrated diagnostics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Molecular imaging has become part of standard care for many types of cancer, providing unique information that enables physicians to personalize patient care. In fact, the biological activity of cells begins to change when cancer occurs and abnormal cellular activity begins to affect body tissue and structures, causing anatomical changes. Molecular imaging excels at detecting the cellular changes that occur early in the course of disease, often well before structural changes can be seen on CT and MR images. In addition to this diagnostic function, molecular imaging provides powerful means to noninvasively characterize diseases and intimately couple targeted therapeutic entities with noninvasive imaging that yields information on the presence of defined molecular targets before, during, and after cognate therapy (i.e. theranostics).

This Special Issue, “Cancer Molecular Imaging”, will cover a selection of recent research topics and current review articles in the field of molecular imaging in oncology.

Prof. Dr. Luca Giovanella
Guest Editor

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

  • molecular imaging
  • cell proliferation
  • metastases
  • staging
  • single-photon emission computed tomography (SPECT)
  • positron emission tomography (PET)
  • “in vivo” spectroscopy
  • theranostics
  • response assessment

Published Papers (7 papers)

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Research

Jump to: Review

13 pages, 2171 KiB  
Article
Feasibility of Imaging EpCAM Expression in Ovarian Cancer Using Radiolabeled DARPin Ec1
by Anzhelika Vorobyeva, Elena Konovalova, Tianqi Xu, Alexey Schulga, Mohamed Altai, Javad Garousi, Sara S. Rinne, Anna Orlova, Vladimir Tolmachev and Sergey Deyev
Int. J. Mol. Sci. 2020, 21(9), 3310; https://doi.org/10.3390/ijms21093310 - 7 May 2020
Cited by 19 | Viewed by 3981
Abstract
Epithelial cell adhesion molecule (EpCAM) is overexpressed in 55%–75% of ovarian carcinomas (OC). EpCAM might be used as a target for a treatment of disseminated OC. Designed ankyrin repeats protein (DARPin) Ec1 is a small (18 kDa) protein, which binds to EpCAM with [...] Read more.
Epithelial cell adhesion molecule (EpCAM) is overexpressed in 55%–75% of ovarian carcinomas (OC). EpCAM might be used as a target for a treatment of disseminated OC. Designed ankyrin repeats protein (DARPin) Ec1 is a small (18 kDa) protein, which binds to EpCAM with subnanomolar affinity. We tested a hypothesis that Ec1 labeled with a non-residualizing label might serve as a companion imaging diagnostic for stratification of patients for EpCAM-targeting therapy. Ec1 was labeled with 125I using N-succinimidyl-para-iodobenzoate. Binding affinity, specificity, and cellular processing of [125I]I-PIB-Ec1 were evaluated using SKOV-3 and OVCAR-3 ovarian carcinoma cell lines. Biodistribution and tumor-targeting properties of [125I]I-PIB-Ec1 were studied in Balb/c nu/nu mice bearing SKOV-3 and OVCAR-3 xenografts. EpCAM-negative Ramos lymphoma xenografts served as specificity control. Binding of [125I]I-PIB-Ec1 to ovarian carcinoma cell lines was highly specific and had affinity in picomolar range. Slow internalization of [125I]I-PIB-Ec1 by OC cells confirmed utility of non-residualizing label for in vivo imaging. [125I]I-PIB-Ec1 provided 6 h after injection tumor-to-blood ratios of 30 ± 11 and 48 ± 12 for OVCAR-3 and SKOV-3 xenografts, respectively, and high contrast to other organs. Tumor targeting was highly specific. Saturation of tumor uptake at a high dose of Ec1 in SKOV-3 model provided a rationale for dose selection in further studies using therapeutic conjugates of Ec1 for targeted therapy. In conclusion, [125I]I-PIB-Ec1 is a promising agent for visualizing EpCAM expression in OC. Full article
(This article belongs to the Special Issue Cancer Molecular Imaging)
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14 pages, 1327 KiB  
Article
Radiolabeled Human Monoclonal Antibody 067-213 has the Potential for Noninvasive Quantification of CD73 Expression
by Hitomi Sudo, Atsushi B. Tsuji, Aya Sugyo, Gene Kurosawa, Yoshikazu Kurosawa, David Alexander, Hiroyuki Tsuda, Tsuneo Saga and Tatsuya Higashi
Int. J. Mol. Sci. 2020, 21(7), 2304; https://doi.org/10.3390/ijms21072304 - 26 Mar 2020
Cited by 5 | Viewed by 2662
Abstract
Background: CD73 is an ectonucleotidase regulating extracellular adenosine concentration and plays an important role in adenosine-mediated immunosuppressive pathways. The efficacy of CD73-targeted therapy depends on the expression levels of CD73; therefore, monitoring CD73 status in cancer patients would provide helpful information for selection [...] Read more.
Background: CD73 is an ectonucleotidase regulating extracellular adenosine concentration and plays an important role in adenosine-mediated immunosuppressive pathways. The efficacy of CD73-targeted therapy depends on the expression levels of CD73; therefore, monitoring CD73 status in cancer patients would provide helpful information for selection of patients who would benefit from CD73-targeted therapy. Here, we evaluated the ability of 111In-labeled antibody 067-213, which has high affinity for human CD73, to act as a noninvasive imaging probe. Methods: Cell binding and competitive inhibition assays for 111In-labeled 067-213 were conducted using MIAPaCa-2 (high CD73 expression) and A431 (low CD73 expression) cells. For in vivo assessments, biodistribution and SPECT/CT studies were conducted in MIAPaCa-2 and A431 tumor-bearing mice. To estimate the absorbed dose in humans, biodistribution and SPECT/CT studies were conducted in healthy rats. Results: 111In-labeled 067-213 bound to MIAPaCa-2 and A431 cells in a CD73-dependent manner and the affinity loss after 111In-labeling was limited. Biodistribution and SPECT/CT studies with 111In-labeled 067-213 in mice showed high uptake in MIAPaCa-2 tumors and lower uptake in A431 tumors. In rats, the probe did not show high uptake in normal organs, including endogenously CD73-expressing organs. The estimated absorbed doses in humans were reasonably low. Conclusions: 111In-labeled 067-213 showed CD73-expression-dependent tumor uptake and low uptake in normal organs and tissues. Radiolabeled 067-213 holds promise as an imaging probe for noninvasive evaluation of CD73 expression levels in patients. Our data encourage further clinical studies to clarify a role for CD73 monitoring in patients receiving CD73-targeted immune therapy. Full article
(This article belongs to the Special Issue Cancer Molecular Imaging)
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16 pages, 2821 KiB  
Article
Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules
by Sara S. Rinne, Charles Dahlsson Leitao, Zahra Saleh-nihad, Bogdan Mitran, Vladimir Tolmachev, Stefan Ståhl, John Löfblom and Anna Orlova
Int. J. Mol. Sci. 2020, 21(6), 1972; https://doi.org/10.3390/ijms21061972 - 13 Mar 2020
Cited by 8 | Viewed by 3285
Abstract
HER3-binding affibody molecules are a promising format for visualization of HER3 expression. Cobalt-55, a positron-emitting isotope, with a half-life of 17.5 h, allows for next-day imaging. We investigated the influence of the charge of the radiocobalt–chelator complex on the biodistribution of anti-HER3 affibody [...] Read more.
HER3-binding affibody molecules are a promising format for visualization of HER3 expression. Cobalt-55, a positron-emitting isotope, with a half-life of 17.5 h, allows for next-day imaging. We investigated the influence of the charge of the radiocobalt–chelator complex on the biodistribution of anti-HER3 affibody molecule (HE)3-ZHER3 and compared the best radiocobalt-labeled variant with a recently optimized gallium-labeled variant. Affibody conjugates (HE)3-ZHER3-X (X = NOTA, NODAGA, DOTA, DOTAGA) were labeled with [57Co]Co (surrogate for 55Co). Affinity measurements, binding specificity and cellular processing were studied in two HER3-expressing cancer cell lines. Biodistribution was studied 3 and 24 h post-injection (pi) in mice with HER3-expressing BxPC-3 xenografts and compared to [68Ga]Ga-(HE)3-ZHER3-NODAGA. Micro-single-photon emission tomography/computed tomography (microSPECT/CT) and micro-positron emission tomography/computed tomography (microPET/CT) imaging was performed 3 and 24 h pi. Stably labeled conjugates bound to HER3 with subnanomolar affinity. [57Co]Co-(HE)3-ZHER3-DOTA had the best tumor retention and a significantly lower concentration in blood than other conjugates, leading to superior tumor-to-blood and tumor-to-liver ratios 24 h pi. Compared to [68Ga]Ga-(HE)3-ZHER3-NODAGA 3 h pi, [57Co]Co-(HE)3-ZHER3-DOTA provided superior imaging contrast in liver 24 h pi. Concluding, the composition and charge of the [57Co]Co–chelator complex influenced the uptake in tumors and normal tissue. [57Co]Co-(HE)3-ZHER3-DOTA provided the best imaging properties among the cobalt-labeled conjugates. Delayed imaging of HER3 expression with [57Co]Co-(HE)3-ZHER3-DOTA improved imaging contrast compared to early-time-point imaging with [68Ga]Ga-(HE)3-ZHER3-NODAGA. Full article
(This article belongs to the Special Issue Cancer Molecular Imaging)
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18 pages, 5489 KiB  
Article
What is the Best Radionuclide for Immuno-PET of Multiple Myeloma? A Comparison Study Between 89Zr- and 64Cu-Labeled Anti-CD138 in a Preclinical Syngeneic Model
by Clément Bailly, Sébastien Gouard, François Guérard, Benjamin Chalopin, Thomas Carlier, Alain Faivre-Chauvet, Patricia Remaud-Le Saëc, Mickaël Bourgeois, Nicolas Chouin, Latifa Rbah-Vidal, Raphaël Tripier, Ferid Haddad, Françoise Kraeber-Bodéré, Caroline Bodet-Milin and Michel Chérel
Int. J. Mol. Sci. 2019, 20(10), 2564; https://doi.org/10.3390/ijms20102564 - 24 May 2019
Cited by 20 | Viewed by 4638
Abstract
Although positron emission tomography (PET) imaging with 18-Fluorodeoxyglucose (18F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker for the identification of myeloma cells and could be [...] Read more.
Although positron emission tomography (PET) imaging with 18-Fluorodeoxyglucose (18F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker for the identification of myeloma cells and could be used in phenotype tumor imaging. In this study, we used an anti-CD138 murine antibody (9E7.4) radiolabeled with copper-64 (64Cu) or zirconium-89 (89Zr) and compared them in a syngeneic mouse model to select the optimal tracers for MM PET imaging. Then, 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for 64Cu and 89Zr labeling, respectively. 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 antibodies were evaluated by PET imaging and biodistribution studies in C57BL/KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions and were compared to 18F-FDG-PET imaging. In biodistribution and PET studies, 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 displayed comparable good tumor uptake of subcutaneous tumors. On the bone lesions, PET imaging with 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 showed higher uptake than with 18F-FDG-PET. Comparison of both 9E7.4 conjugates revealed higher nonspecific bone uptakes of 89Zr-DFO-9E7.4 than 64Cu-TE2A-9E7.4. Because of free 89Zr’s tropism for bone when using 89Zr-anti-CD138, 64Cu-anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific new imaging radiopharmaceutical agent in MM. Full article
(This article belongs to the Special Issue Cancer Molecular Imaging)
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Review

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10 pages, 218 KiB  
Review
PSMA-Targeting Positron Emission Agents for Imaging Solid Tumors Other Than Non-Prostate Carcinoma: A Systematic Review
by Christophe Van de Wiele, Mike Sathekge, Bart de Spiegeleer, Pieter Jan de Jonghe, Laurence Beels and Alex Maes
Int. J. Mol. Sci. 2019, 20(19), 4886; https://doi.org/10.3390/ijms20194886 - 2 Oct 2019
Cited by 32 | Viewed by 3475
Abstract
Despite its name, prostate-specific membrane antigen (PSMA) has been shown using immunohistochemistry (IHC) to also be over-expressed in the tumor neovasculature of a wide variety of solid tumors other than prostate carcinoma. Accordingly, positron-emitting radiolabeled small molecules targeting PSMA, initially developed for positron [...] Read more.
Despite its name, prostate-specific membrane antigen (PSMA) has been shown using immunohistochemistry (IHC) to also be over-expressed in the tumor neovasculature of a wide variety of solid tumors other than prostate carcinoma. Accordingly, positron-emitting radiolabeled small molecules targeting PSMA, initially developed for positron emission tomography in prostate carcinomas, are currently being explored for their staging and restaging potential as an alternative imaging modality in other solid tumor types where 18-F-fluorodeoxyglucose (FDG)-PET imaging has low diagnostic accuracy. In this paper, the currently available literature in this field is reviewed. Preliminary, mainly retrospective studies are encouraging, with evidence of improved diagnostic sensitivity and specificity in clear cell renal carcinoma, glioma, and hepatocellular carcinoma, leading to a change in patient management in several patients. However, the results published thus far warrant confirmation by larger prospective studies additionally assessing the longitudinal impact on patient outcomes. Full article
(This article belongs to the Special Issue Cancer Molecular Imaging)
16 pages, 1011 KiB  
Review
Diagnostic Performance and Prognostic Value of PET/CT with Different Tracers for Brain Tumors: A Systematic Review of Published Meta-Analyses
by Giorgio Treglia, Barbara Muoio, Gianluca Trevisi, Maria Vittoria Mattoli, Domenico Albano, Francesco Bertagna and Luca Giovanella
Int. J. Mol. Sci. 2019, 20(19), 4669; https://doi.org/10.3390/ijms20194669 - 20 Sep 2019
Cited by 70 | Viewed by 4439
Abstract
Background: Several meta-analyses reporting data on the diagnostic performance or prognostic value of positron emission tomography (PET) with different tracers in detecting brain tumors have been published so far. This review article was written to summarize the evidence-based data in these settings. Methods: [...] Read more.
Background: Several meta-analyses reporting data on the diagnostic performance or prognostic value of positron emission tomography (PET) with different tracers in detecting brain tumors have been published so far. This review article was written to summarize the evidence-based data in these settings. Methods: We have performed a comprehensive literature search of meta-analyses published in the Cochrane library and PubMed/Medline databases (from inception through July 2019) about the diagnostic performance or prognostic value of PET with different tracers in patients with brain tumors. Results: We have summarized the results of 24 retrieved meta-analyses on the use of PET or PET/computed tomography (CT) with different tracers in brain tumors. The tracers included were: fluorine-18 fluorodeoxyglucose (18F-FDG), carbon-11 methionine (11C-methionine), fluorine-18 fluoroethyltyrosine (18F-FET), fluorine-18 dihydroxyphenylalanine (18F-FDOPA), fluorine-18 fluorothymidine (18F-FLT), and carbon-11 choline (11C-choline). Evidence-based data demonstrated good diagnostic performance of PET with different tracers in detecting brain tumors, in particular, radiolabelled amino acid tracers showed the highest diagnostic performance values. All the PET tracers evaluated had significant prognostic value in patients with glioma. Conclusions: Evidence-based data showed a good diagnostic performance for some PET tracers in specific indications and significant prognostic value in brain tumors. Full article
(This article belongs to the Special Issue Cancer Molecular Imaging)
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13 pages, 224 KiB  
Review
The Evaluation of Response to Immunotherapy in Metastatic Renal Cell Carcinoma: Open Challenges in the Clinical Practice
by Alessandra Raimondi, Giovanni Randon, Pierangela Sepe, Melanie Claps, Elena Verzoni, Filippo de Braud and Giuseppe Procopio
Int. J. Mol. Sci. 2019, 20(17), 4263; https://doi.org/10.3390/ijms20174263 - 30 Aug 2019
Cited by 20 | Viewed by 3578
Abstract
Immunotherapy has changed the therapeutic scenario of metastatic renal cell carcinoma (mRCC), however the evaluation of disease response to immune-checkpoint inhibitors is still an open challenge. Response evaluation criteria in solid tumors (RECIST) 1.1 criteria are the cornerstone of response assessment to anti-neoplastic [...] Read more.
Immunotherapy has changed the therapeutic scenario of metastatic renal cell carcinoma (mRCC), however the evaluation of disease response to immune-checkpoint inhibitors is still an open challenge. Response evaluation criteria in solid tumors (RECIST) 1.1 criteria are the cornerstone of response assessment to anti-neoplastic treatments, but the use of anti-programmed death receptor 1 (PD1) and other immunotherapeutic agents has shown atypical patterns of response such as pseudoprogression. Therefore, immune-modified criteria have been developed in order to more accurately categorize the disease response, even though their use in the everyday clinical practice is still limited. In this review we summarize the available evidence on this topic, with particular focus on the application of immune-modified criteria in the setting of mRCC. Full article
(This article belongs to the Special Issue Cancer Molecular Imaging)
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