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Cancer Molecular Imaging 2.0
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Cancer Molecular Imaging 2.0

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

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 16033

Special Issue Editor

Prof. Dr. Christophe V. van de Wiele

E-Mail Website
Guest Editor
Department of Nuclear Medicine and Radiology, University Ghent, 9000 GHent, Belgium

Special Issue Information

Dear Colleagues,

The unraveling of the underlying relevant molecular pathways that drive tumor growth, through genomics, proteomics, single cell analysis, and high throughput phenotypic assaysas as witnessed in the last three decades, has led to a more personalized, targeted treatment approach of cancer patients. As targeted treatment implies that only a limited number of patients will benefit from a specific type of treatment, adequate selection of these patients prior to treatment initiation is of paramount importance. As opposed to morphological imaging, both single photon emission tomography (SPECT) and positron emission tomography (PET) using specific radiolabeled probes allow for non-invasive whole body imaging of the specific biological and functional characteristics that are being targeted by targeted therapies. Accordingly, the role of SPECT and PET imaging in personalized cancer patient management is increasing. This issue of Int J Mol Sci aims to give an update on the current status of PET and SPECT imaging in personalized cancer treatment, focusing on the underlying molecular pathways that are being targeted.

Prof. Dr. Christophe V. van de Wiele
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 (4 papers)

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Research

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20 pages, 2920 KiB  
Article
Preclinical Evaluation of 99mTc-ZHER2:41071, a Second-Generation Affibody-Based HER2-Visualizing Imaging Probe with a Low Renal Uptake
by Maryam Oroujeni, Sara S. Rinne, Anzhelika Vorobyeva, Annika Loftenius, Joachim Feldwisch, Per Jonasson, Vladimir Chernov, Anna Orlova, Fredrik Y. Frejd and Vladimir Tolmachev
Int. J. Mol. Sci. 2021, 22(5), 2770; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052770 - 09 Mar 2021
Cited by 17 | Viewed by 3539
Abstract
Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [99mTc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively [...] Read more.
Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [99mTc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a second-generation affibody molecule (designated ZHER2:41071) with a new improved scaffold has been prepared and characterized. HER2-binding, biodistribution, and tumour-targeting properties of [99mTc]Tc-labelled ZHER2:41071 were investigated. These properties were compared with properties of the first-generation affibody molecules, [99mTc]Tc-ZHER2:V2 and [99mTc]Tc-ZHER2:2395. [99mTc]Tc-ZHER2:41071 bound specifically to HER2 expressing cells with an affinity of 58 ± 2 pM. The renal uptake for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 was 25–30 fold lower when compared with [99mTc]Tc-ZHER2:2395. The uptake in tumour and kidney for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 in SKOV-3 xenografts was similar. In conclusion, an extensive re-engineering of the scaffold did not compromise imaging properties of the affibody molecule labelled with 99mTc using a GGGC chelator. The new probe, [99mTc]Tc-ZHER2:41071 provided the best tumour-to-blood ratio compared to HER2-imaging probes for single photon emission computed tomography (SPECT) described in the literature so far. [99mTc]Tc-ZHER2:41071 is a promising candidate for further clinical translation studies. Full article
(This article belongs to the Special Issue Cancer Molecular Imaging 2.0)
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Review

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19 pages, 958 KiB  
Review
Molecular Imaging of Angiogenesis in Oncology: Current Preclinical and Clinical Status
by Alexandru Florea, Felix M. Mottaghy and Matthias Bauwens
Int. J. Mol. Sci. 2021, 22(11), 5544; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115544 - 24 May 2021
Cited by 17 | Viewed by 3927
Abstract
Angiogenesis is an active process, regulating new vessel growth, and is crucial for the survival and growth of tumours next to other complex factors in the tumour microenvironment. We present possible molecular imaging approaches for tumour vascularisation and vitality, focusing on radiopharmaceuticals (tracers). [...] Read more.
Angiogenesis is an active process, regulating new vessel growth, and is crucial for the survival and growth of tumours next to other complex factors in the tumour microenvironment. We present possible molecular imaging approaches for tumour vascularisation and vitality, focusing on radiopharmaceuticals (tracers). Molecular imaging in general has become an integrated part of cancer therapy, by bringing relevant insights on tumour angiogenic status. After a structured PubMed search, the resulting publication list was screened for oncology related publications in animals and humans, disregarding any cardiovascular findings. The tracers identified can be subdivided into direct targeting of angiogenesis (i.e., vascular endothelial growth factor, laminin, and fibronectin) and indirect targeting (i.e., glucose metabolism, hypoxia, and matrix metallo-proteases, PSMA). Presenting pre-clinical and clinical data of most tracers proposed in the literature, the indirect targeting agents are not 1:1 correlated with angiogenesis factors but do have a strong prognostic power in a clinical setting, while direct targeting agents show most potential and specificity for assessing tumour vascularisation and vitality. Within the direct agents, the combination of multiple targeting tracers into one agent (multimers) seems most promising. This review demonstrates the present clinical applicability of indirect agents, but also the need for more extensive research in the field of direct targeting of angiogenesis in oncology. Although there is currently no direct tracer that can be singled out, the RGD tracer family seems to show the highest potential therefore we expect one of them to enter the clinical routine. Full article
(This article belongs to the Special Issue Cancer Molecular Imaging 2.0)
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39 pages, 3336 KiB  
Review
PET and SPECT Imaging of the EGFR Family (RTK Class I) in Oncology
by Sara S. Rinne, Anna Orlova and Vladimir Tolmachev
Int. J. Mol. Sci. 2021, 22(7), 3663; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073663 - 01 Apr 2021
Cited by 19 | Viewed by 5808
Abstract
The human epidermal growth factor receptor family (EGFR-family, other designations: HER family, RTK Class I) is strongly linked to oncogenic transformation. Its members are frequently overexpressed in cancer and have become attractive targets for cancer therapy. To ensure effective patient care, potential responders [...] Read more.
The human epidermal growth factor receptor family (EGFR-family, other designations: HER family, RTK Class I) is strongly linked to oncogenic transformation. Its members are frequently overexpressed in cancer and have become attractive targets for cancer therapy. To ensure effective patient care, potential responders to HER-targeted therapy need to be identified. Radionuclide molecular imaging can be a key asset for the detection of overexpression of EGFR-family members. It meets the need for repeatable whole-body assessment of the molecular disease profile, solving problems of heterogeneity and expression alterations over time. Tracer development is a multifactorial process. The optimal tracer design depends on the application and the particular challenges of the molecular target (target expression in tumors, endogenous expression in healthy tissue, accessibility). We have herein summarized the recent preclinical and clinical data on agents for Positron Emission Tomography (PET) and Single Photon Emission Tomography (SPECT) imaging of EGFR-family receptors in oncology. Antibody-based tracers are still extensively investigated. However, their dominance starts to be challenged by a number of tracers based on different classes of targeting proteins. Among these, engineered scaffold proteins (ESP) and single domain antibodies (sdAb) show highly encouraging results in clinical studies marking a noticeable trend towards the use of smaller sized agents for HER imaging. Full article
(This article belongs to the Special Issue Cancer Molecular Imaging 2.0)
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14 pages, 1037 KiB  
Review
Apoptosis Imaging in Oncology by Means of Positron Emission Tomography: A Review
by Christophe Van de Wiele, Sezgin Ustmert, Bart De Spiegeleer, Pieter-Jan De Jonghe, Mike Sathekge and Maes Alex
Int. J. Mol. Sci. 2021, 22(5), 2753; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052753 - 09 Mar 2021
Cited by 10 | Viewed by 2297
Abstract
To date, a wide variety of potential PET-apoptosis imaging radiopharmaceuticals targeting apoptosis-induced cell membrane asymmetry and acidification, as well as caspase 3 activation (substrates and inhibitors) have been developed with the purpose of rapidly assessing the response to treatment in cancer patients. Many [...] Read more.
To date, a wide variety of potential PET-apoptosis imaging radiopharmaceuticals targeting apoptosis-induced cell membrane asymmetry and acidification, as well as caspase 3 activation (substrates and inhibitors) have been developed with the purpose of rapidly assessing the response to treatment in cancer patients. Many of these probes were shown to specifically bind to their apoptotic target in vitro and their uptake to be enhanced in the in vivo-xenografted tumours in mice treated by means of chemotherapy, however, to a significantly variable degree. This may, in part, relate to the tumour model used given the fact that different tumour cell lines bear a different sensitivity to a similar chemotherapeutic agent, to differences in the chemotherapeutic concentration and exposure time, as well as to the different timing of imaging performed post-treatment. The best validated cell membrane acidification and caspase 3 targeting radioligands, respectively 18F-ML-10 from the Aposense family and the radiolabelled caspase 3 substrate 18F-CP18, have also been injected in healthy individuals and shown to bear favourable dosimetric and safety characteristics. However, in contrast to, for instance, the 99mTc-HYNIC-Annexin V, neither of both tracers was taken up to a significant degree by the bone marrow in the healthy individuals under study. Removal of white and red blood cells from the bone marrow through apoptosis plays a major role in the maintenance of hematopoietic cell homeostasis. The major apoptotic population in normal bone marrow are immature erythroblasts. While an accurate estimate of the number of immature erythroblasts undergoing apoptosis is not feasible due to their unknown clearance rate, their number is likely substantial given the ineffective quote of the erythropoietic process described in healthy subjects. Thus, the clinical value of both 18F-ML-10 and 18F-CP18 for apoptosis imaging in cancer patients, as suggested by a small number of subsequent clinical phase I/II trials in patients suffering from primary or secondary brain malignancies using 18F-ML-10 and in an ongoing trial in patients suffering from cancer of the ovaries using 18F-CP18, remains to be proven and warrants further investigation. Full article
(This article belongs to the Special Issue Cancer Molecular Imaging 2.0)
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