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Biomedicines
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New Generation Imaging in Oncology 2.0
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New Generation Imaging in Oncology 2.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 17365

Special Issue Editors

Dr. Francesco Ceci

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Guest Editor
Nuclear Medicine Division, European Institute of Oncology (IEO) IRCCS, Milan, Italy
Interests: clinical and preclinical application of prostate-specific membrane antigen (PSMA) for imaging and therapy in prostate cancer; clinical application of new generation imaging procedures in genitourinary malignancy; clinical application of predictive models in prostate cancer; clinical and preclinical application of radioligand therapy (RLT) in oncology; translational imaging and development of new PET radiopharmaceuticals in oncology
Special Issues, Collections and Topics in MDPI journals
Dr. Marcus Unterrainer

E-Mail Website
Guest Editor
Department of Radiology, Klinikum der Universität München, Munich, Germany
Interests: radiology; nuclear medicine
Dr. Michel Eisenblätter

E-Mail Website
Guest Editor
King’s College, University of Freiburg, London, UK
Interests: molecular imaging; oncologic imaging; tumor immunology; optical and hybrid imaging
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The introduction of molecular imaging, namely positron emission tomography (PET) imaging, in oncology has already changed the clinical outcomes and therapeutic management of oncological patients. Several PET radiopharmaceuticals have been proposed in oncology over the last decade, and these diagnostic techniques are now currently placed under the umbrella term “new-generation imaging”.

The most successful approaches proposed for PET imaging, other than FDG-PET, have been receptorial tracers targeting the somatostatin receptors (SSRs) and the prostate-specific membrane antigen (PSMA), proposed to investigate neuroendocrine tumors and prostate cancer, respectively. Both of these in vivo biomarkers can be used both for diagnostic (PET imaging) and therapeutic (radioligand therapy) purposes, and are currently considered the cornerstones of the theranostic approach.

However, FDG-PET still holds an innovative position when considering its application to evaluate the efficacy of new-generation therapeutic approaches in oncology, like immunotherapy, which currently represents one of the most successful treatments for lung cancer and melanoma.

Finally, the application of radiomics in PET imaging is an emerging field. Radiomics is defined as the high-throughput extraction of quantitative features from medical images. This approach provides high-dimensional data describing the shape and texture of tumors captured in different diagnostic procedures. The radiomics features are believed to contain information that reflects the underlying tumor pathophysiology, and allows for the evaluation of tumor heterogeneity.

This Special Issue aims to collect innovative studies regarding the translational imaging of new-generation PET imaging in oncology. Pre-clinical studies are welcome. Comprehensive reviews regarding these innovative diagnostic and therapeutic approaches will be also considered.

Dr. Francesco Ceci
Dr. Marcus Unterrainer
Dr. Michel Eisenblätter
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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • PSMA
  • radiomics
  • immunotherapy
  • immuno-PET
  • radio-ligand therapy
  • textural features
  • machine learning
  • DOTA-TOC
  • prostate cancer
  • lung cancer
  • melanoma
  • neuroendocrine tumors
  • NET

Published Papers (6 papers)

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Research

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12 pages, 1420 KiB  
Article
Extrahepatic Disease in Hepatocellular Carcinoma: Do We Always Need Whole-Body CT or Is Liver MRI Sufficient? A Subanalysis of the SORAMIC Trial
by Thomas Geyer, Philipp M. Kazmierczak, Ingo G. Steffen, Peter Malfertheiner, Bora Peynircioglu, Christian Loewe, Otto van Delden, Vincent Vandecaveye, Bernhard Gebauer, Maciej Pech, Christian Sengel, Irene Bargellini, Roberto Iezzi, Alberto Benito, Christoph J. Zech, Antonio Gasbarrini, Kerstin Schütte, Jens Ricke and Max Seidensticker
Biomedicines 2022, 10(5), 1156; https://doi.org/10.3390/biomedicines10051156 - 18 May 2022
Viewed by 1842
Abstract
Background: To investigate whole-body contrast-enhanced CT and hepatobiliary contrast liver MRI for the detection of extrahepatic disease (EHD) in hepatocellular carcinoma (HCC) and to quantify the impact of EHD on therapy decision. Methods: In this post-hoc analysis of the prospective phase II open-label, [...] Read more.
Background: To investigate whole-body contrast-enhanced CT and hepatobiliary contrast liver MRI for the detection of extrahepatic disease (EHD) in hepatocellular carcinoma (HCC) and to quantify the impact of EHD on therapy decision. Methods: In this post-hoc analysis of the prospective phase II open-label, multicenter, randomized controlled SORAMIC trial, two blinded readers independently analyzed the whole-body contrast-enhanced CT and gadoxetic acid-enhanced liver MRI data sets of 538 HCC patients. EHD (defined as tumor manifestation outside the liver) detection rates of the two imaging modalities were compared using multiparametric statistical tests. In addition, the most appropriate treatment recommendation was determined by a truth panel. Results: EHD was detected significantly more frequently in patients with portal vein infiltration (21% vs. 10%, p < 0.001), macrovascular infiltration (22% vs. 9%, p < 0.001), and bilobar liver involvement (18% vs. 9%, p = 0.006). Further on, the maximum lesion diameter in patients with EHD was significantly higher (8.2 cm vs. 5.8 cm, p = 0.002). CT detected EHD in significantly more patients compared to MRI in both reader groups (p < 0.001). Higher detection rates of EHD in CT led to a change in management only in one patient since EHD was predominantly present in patients with locally advanced HCC, in whom palliative treatment is the standard of care. Conclusions: Whole-body contrast-enhanced CT shows significantly higher EHD detection rates compared to hepatobiliary contrast liver MRI. However, the higher detection rate did not yield a significant impact on patient management in advanced HCC. Full article
(This article belongs to the Special Issue New Generation Imaging in Oncology 2.0)
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16 pages, 2781 KiB  
Article
Total Tumor Volume on 18F-PSMA-1007 PET as Additional Imaging Biomarker in mCRPC Patients Undergoing PSMA-Targeted Alpha Therapy with 225Ac-PSMA-I&T
by Lena M. Unterrainer, Leonie Beyer, Mathias J. Zacherl, Franz J. Gildehaus, Andrei Todica, Sophie C. Kunte, Adrien Holzgreve, Gabriel T. Sheikh, Annika Herlemann, Jozefina Casuscelli, Matthias Brendel, Nathalie L. Albert, Vera Wenter, Nina-Sophie Schmidt-Hegemann, Wolfgang G. Kunz, Clemens C. Cyran, Jens Ricke, Christian G. Stief, Peter Bartenstein, Harun Ilhan and Marcus Unterraineradd Show full author list remove Hide full author list
Biomedicines 2022, 10(5), 946; https://doi.org/10.3390/biomedicines10050946 - 20 Apr 2022
Cited by 6 | Viewed by 2117
Abstract
Background: PSMA-based alpha therapy using 225Ac-PSMA-I&T provides treatment for metastatic castration-resistant prostate cancer (mCRPC), even after the failure of 177Lu-PSMA radioligand therapy (RLT). In clinical routine, the total tumor volume (TTV) on PSMA PET impacts therapy outcomes and plays an increasing [...] Read more.
Background: PSMA-based alpha therapy using 225Ac-PSMA-I&T provides treatment for metastatic castration-resistant prostate cancer (mCRPC), even after the failure of 177Lu-PSMA radioligand therapy (RLT). In clinical routine, the total tumor volume (TTV) on PSMA PET impacts therapy outcomes and plays an increasing role in mCRPC patients. Hence, we aimed to assess TTV and its changes during 225Ac-PSMA-I&T RLT. Methods: mCRPC patients undergoing RLT with 225Ac-PSMA-I&T with available 18F-PSMA-1007 PET/CT prior to therapy initiation were included. TTV was assessed in all patients using established cut-off values. Image derived, clinical and biochemistry parameters (PSA, LDH, AP, pain score) were analyzed prior to and after two cycles of 225Ac-PSMA. Changes in TTV and further parameters were directly compared and then correlated with established response criteria, such as RECIST 1.1 or mPERCIST. Results: 13 mCRPC patients were included. The median overall survival (OS) was 10 months. Prior to 225Ac-PSMA RLT, there was no significant correlation between TTV with other clinical parameters (p > 0.05 each). Between short-term survivors (STS, <10 months OS) and long-term survivors (LTS, ≥10 months OS), TTV and PSA were comparable (p = 0.592 & p = 0.286, respectively), whereas AP was significantly lower in the LTS (p = 0.029). A total of 7/13 patients completed two cycles and underwent a follow-up 18F-PSMA-1007 PET/CT. Among these patients, there was a significant decrease in TTV (median 835 vs. 201 mL, p = 0.028) and PSA (median 687 ng/dL vs. 178 ng/dL, p = 0.018) after two cycles of 225Ac-PSMA RLT. Here, percentage changes of TTV after two cycles showed no direct correlation to all other clinical parameters (p > 0.05 each). In two patients, new PET-avid lesions were detected on 18F-PSMA-1007 PET/CT. However, TTV and PSA were decreasing or stable. Conclusion: PET-derived assessment of TTV is an easily applicable imaging biomarker independent of other established parameters prior to 225Ac-PSMA RLT in these preliminary follow-up data. Even after the failure of 177Lu-PSMA, patients with extensive TTV seem to profit from RLT. All but one patient who was eligible for ≥2 cycles of 225Ac-PSMA-RLT demonstrated drastic TTV decreases without direct correlation to other biomarkers, such as serum PSA changes. Changes in TTV might hence improve the response assessment compared to standard classifiers by reflecting the current tumor load independent of the occurrence of new lesions. Full article
(This article belongs to the Special Issue New Generation Imaging in Oncology 2.0)
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14 pages, 2145 KiB  
Article
Longitudinal [18F]GE-180 PET Imaging Facilitates In Vivo Monitoring of TSPO Expression in the GL261 Glioblastoma Mouse Model
by Adrien Holzgreve, Dennis Pötter, Matthias Brendel, Michael Orth, Lorraine Weidner, Lukas Gold, Maximilian A. Kirchner, Laura M. Bartos, Lena M. Unterrainer, Marcus Unterrainer, Katja Steiger, Louisa von Baumgarten, Maximilian Niyazi, Claus Belka, Peter Bartenstein, Markus J. Riemenschneider, Kirsten Lauber and Nathalie L. Albert
Biomedicines 2022, 10(4), 738; https://doi.org/10.3390/biomedicines10040738 - 22 Mar 2022
Cited by 8 | Viewed by 2767
Abstract
The 18 kDa translocator protein (TSPO) is increasingly recognized as an interesting target for the imaging of glioblastoma (GBM). Here, we investigated TSPO PET imaging and autoradiography in the frequently used GL261 glioblastoma mouse model and aimed to generate insights into the temporal [...] Read more.
The 18 kDa translocator protein (TSPO) is increasingly recognized as an interesting target for the imaging of glioblastoma (GBM). Here, we investigated TSPO PET imaging and autoradiography in the frequently used GL261 glioblastoma mouse model and aimed to generate insights into the temporal evolution of TSPO radioligand uptake in glioblastoma in a preclinical setting. We performed a longitudinal [18F]GE-180 PET imaging study from day 4 to 14 post inoculation in the orthotopic syngeneic GL261 GBM mouse model (n = 21 GBM mice, n = 3 sham mice). Contrast-enhanced computed tomography (CT) was performed at the day of the final PET scan (±1 day). [18F]GE-180 autoradiography was performed on day 7, 11 and 14 (ex vivo: n = 13 GBM mice, n = 1 sham mouse; in vitro: n = 21 GBM mice; n = 2 sham mice). Brain sections were also used for hematoxylin and eosin (H&E) staining and TSPO immunohistochemistry. [18F]GE-180 uptake in PET was elevated at the site of inoculation in GBM mice as compared to sham mice at day 11 and later (at day 14, TBRmax +27% compared to sham mice, p = 0.001). In GBM mice, [18F]GE-180 uptake continuously increased over time, e.g., at day 11, mean TBRmax +16% compared to day 4, p = 0.011. [18F]GE-180 uptake as depicted by PET was in all mice co-localized with contrast-enhancement in CT and tissue-based findings. [18F]GE-180 ex vivo and in vitro autoradiography showed highly congruent tracer distribution (r = 0.99, n = 13, p < 0.001). In conclusion, [18F]GE-180 PET imaging facilitates non-invasive in vivo monitoring of TSPO expression in the GL261 GBM mouse model. [18F]GE-180 in vitro autoradiography is a convenient surrogate for ex vivo autoradiography, allowing for straightforward identification of suitable models and scan time-points on previously generated tissue sections. Full article
(This article belongs to the Special Issue New Generation Imaging in Oncology 2.0)
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16 pages, 11200 KiB  
Article
Relevance of Dynamic 18F-DOPA PET Radiomics for Differentiation of High-Grade Glioma Progression from Treatment-Related Changes
by Shamimeh Ahrari, Timothée Zaragori, Laura Rozenblum, Julien Oster, Laëtitia Imbert, Aurélie Kas and Antoine Verger
Biomedicines 2021, 9(12), 1924; https://doi.org/10.3390/biomedicines9121924 - 16 Dec 2021
Cited by 12 | Viewed by 2467
Abstract
This study evaluates the relevance of 18F-DOPA PET static and dynamic radiomics for differentiation of high-grade glioma (HGG) progression from treatment-related changes (TRC) by comparing diagnostic performances to the current PET imaging standard of care. Eighty-five patients with histologically confirmed HGG and [...] Read more.
This study evaluates the relevance of 18F-DOPA PET static and dynamic radiomics for differentiation of high-grade glioma (HGG) progression from treatment-related changes (TRC) by comparing diagnostic performances to the current PET imaging standard of care. Eighty-five patients with histologically confirmed HGG and investigated by dynamic 18F-FDOPA PET in two institutions were retrospectively selected. ElasticNet logistic regression, Random Forest and XGBoost machine models were trained with different sets of features—radiomics extracted from static tumor-to-background-ratio (TBR) parametric images, radiomics extracted from time-to-peak (TTP) parametric images, as well as combination of both—in order to discriminate glioma progression from TRC at 6 months from the PET scan. Diagnostic performances of the models were compared to a logistic regression model with TBRmean ± clinical features used as reference. Training was performed on data from the first center, while external validation was performed on data from the second center. Best radiomics models showed only slightly better performances than the reference model (respective AUCs of 0.834 vs. 0.792, p < 0.001). Our current results show similar findings at the multicentric level using different machine learning models and report a marginal additional value for TBR static and TTP dynamic radiomics over the classical analysis based on TBR values. Full article
(This article belongs to the Special Issue New Generation Imaging in Oncology 2.0)
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Review

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14 pages, 1002 KiB  
Review
FDG and Non-FDG Radiopharmaceuticals for PET Imaging in Invasive Lobular Breast Carcinoma
by Laura Gilardi, Lighea Simona Airò Farulla, Giuseppe Curigliano, Giovanni Corso, Maria Cristina Leonardi and Francesco Ceci
Biomedicines 2023, 11(5), 1350; https://doi.org/10.3390/biomedicines11051350 - 03 May 2023
Cited by 1 | Viewed by 2666
Abstract
Invasive lobular cancer (ILC) is the second most frequent histological type of breast cancer (BC) and includes a heterogeneous spectrum of diseases with unique characteristics, especially the infiltrative growth pattern and metastatic spread. [18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is extensively [...] Read more.
Invasive lobular cancer (ILC) is the second most frequent histological type of breast cancer (BC) and includes a heterogeneous spectrum of diseases with unique characteristics, especially the infiltrative growth pattern and metastatic spread. [18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is extensively used in oncology and BC patient evaluation. Its role in ILCs is considered suboptimal due to its low FDG avidity. Therefore, ILCs could benefit from molecular imaging with non-FDG tracers that target other specific pathways, contributing to precision medicine. This narrative review aims to summarize the current literature on the use of FDG-PET/CT in ILC and to discuss future opportunities given by the development of innovative non-FDG radiotracers. Full article
(This article belongs to the Special Issue New Generation Imaging in Oncology 2.0)
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14 pages, 568 KiB  
Review
Imaging Cancer-Associated Fibroblasts (CAFs) with FAPi PET
by Laura Gilardi, Lighea Simona Airò Farulla, Emre Demirci, Ilaria Clerici, Emanuela Omodeo Salè and Francesco Ceci
Biomedicines 2022, 10(3), 523; https://doi.org/10.3390/biomedicines10030523 - 23 Feb 2022
Cited by 36 | Viewed by 4452
Abstract
The tumor microenvironment (TME) surrounding tumor cells is a complex and highly dynamic system that promotes tumorigenesis. Cancer-associated fibroblasts (CAFs) are key elements in TME playing a pivotal role in cancer cells’ proliferation and metastatic spreading. Considering the high expression of the fibroblast [...] Read more.
The tumor microenvironment (TME) surrounding tumor cells is a complex and highly dynamic system that promotes tumorigenesis. Cancer-associated fibroblasts (CAFs) are key elements in TME playing a pivotal role in cancer cells’ proliferation and metastatic spreading. Considering the high expression of the fibroblast activation protein (FAP) on the cell membrane, CAFs emerged as appealing TME targets, namely for molecular imaging, leading to a pan-tumoral approach. Therefore, FAP inhibitors (FAPis) have recently been developed for PET imaging and radioligand therapy, exploring the clinical application in different tumor sub-types. The present review aimed to describe recent developments regarding radiolabeled FAP inhibitors and evaluate the possible translation of this pan-tumoral approach in clinical practice. At present, the application of FAPi-PET has been explored mainly in single-center studies, generally performed in small and heterogeneous cohorts of oncological patients. However, preliminary results were promising, in particular in low FDG-avid tumors, such as primary liver and gastro-entero-pancreatic cancer, or in regions with an unfavorable tumor-to-background ratio at FDG-PET/CT (i.e., brain), and in radiotherapy planning of head and neck tumors. Further promising results have been obtained in the detection of peritoneal carcinomatosis, especially in ovarian and gastric cancer. Data regarding the theranostics approach are still limited at present, and definitive conclusions about its efficacy cannot be drawn at present. Nevertheless, the use of FAPi-based radio-ligand to treat the TME has been evaluated in first-in-human studies and appears feasible. Although the pan-tumoral approach in molecular imaging showed promising results, its real impact in day-to-day clinical practice has yet to be confirmed, and multi-center prospective studies powered for efficacy are needed. Full article
(This article belongs to the Special Issue New Generation Imaging in Oncology 2.0)
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