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Hybrid Molecular Imaging Approaches in Cancer: PET/CT, PET/MRI, and Beyond

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Dear Colleagues,

Hybrid molecular imaging has revolutionized cancer diagnosis, staging, and treatment monitoring by synergistically combining anatomical and functional information. This Special Issue, “Hybrid Molecular Imaging Approaches in Cancer: PET/CT, PET/MRI, and Beyond”, will delve into the latest advancements and future directions in this rapidly evolving field.

Positron emission tomography (PET), integrated into computed tomography (CT) or magnetic resonance imaging (MRI), has become indispensable, offering unparalleled insights into tumor biology and heterogeneity. Combining PET functional imaging with CT enables accurate anatomical localization and quantitative assessment. The integration of PET into MRI offers superior soft-tissue contrast, which is especially valuable in body regions such as the pelvis or the head and neck. Furthermore, hybrid molecular imaging, particularly when combined with radiomics, generates vast datasets, which is essential in training predictive artificial intelligence models.

Beyond these established modalities, this Special Issue will explore emerging hybrid techniques and novel radiotracers, pushing the boundaries of precision oncology. Contributions should highlight innovative applications, challenges, and the potential of these integrated approaches in personalizing cancer management, improving patient outcomes, and guiding targeted therapies.

We invite you to share your cutting-edge work, to enhance our understanding of the transformative role of hybrid imaging in the fight against cancer.

For this Special Issue, original research articles and reviews are welcome. We look forward to receiving your contributions.

Dr. Luca Urso
Guest Editor

Ilham Badrane
Guest Editor Assistant

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12 pages, 830 KB

Open AccessArticle

Can PSMA-Targeting Radiopharmaceuticals Be Useful for Detecting Brain Metastasis of Various Tumors Using Positron Emission Tomography?

by Esra Arslan, Nurhan Ergül, Rahime Şahin, Ediz Beyhan, Özge Erol Fenercioğlu, Yeşim Karagöz, Arzu Algün Gedik, Yakup Bozkaya and Tevfik Fikret Çermik

Cancers 2025, 17(18), 3088; https://doi.org/10.3390/cancers17183088 - 22 Sep 2025

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Abstract

Objective: The high expression of prostate-specific membrane antigen (PSMA) associated with neovascularization in non-prostatic malignant tumors and metastatic lesions has been documented in many studies. By taking advantage of the absence of PSMA-related background activity in brain tissue, in recent years, PSMA has been used for the imaging of glial tumors, especially for postoperative follow-up. The aim of this prospective study was to investigate the diagnostic value of ⁶⁸Ga-PSMA-11 PET/CT by comparing ⁶⁸Ga-PSMA-11 PET/CT, ¹⁸F-FDG PET/CT, and MRI findings in patients with brain metastases (BM). Materials and Method: In this prospective study, 27 cases, 11 female and 16 male, with a mean age of 59.48 ± 12.21 years, were included. Patients diagnosed with BM on ¹⁸F-FDG PET/CT or CT/MRI at initial diagnosis or in the follow-up period were included in the study. PET findings of BM lesions obtained from ¹⁸F-FDG and ⁶⁸Ga-PSMA-11 PET/CT imaging, demographic characteristics, histopathological data of the primary foci, and other clinical features were evaluated together. Results: Twenty-four (89%) patients were included in the study for restaging, two (7%) patients for local recurrence assessment, and one (4%) patient for local recurrence and suspicion of additional lesions. The indications for ¹⁸F-FDG PET/CT were breast carcinoma for 37% (n:10), followed by lung carcinoma for 26% (n:7), colorectal adenocarcinoma for 14% (n:4), squamous cell larynx carcinoma for 7% (n:2), gastric signet ring cell carcinoma for 4% (n:1), pancreatic NET3 for 4% (n:1), thyroid papillary carcinoma for 4% (n:1), and malignant melanoma for 4% (n:1). In total, 26/27 included patients had PSMA-positive brain metastases but only one patient had PSMA-negative brain metastases with ⁶⁸Ga-PSMA-11 PET/CT imaging. This patient was followed with a diagnosis of primary larynx squamous carcinoma and had a mass suspected of brain metastases. Further tests and an MRI revealed that the lesion in this patient was a hemorrhagic metastasis. The smallest metastatic focus on ⁶⁸Ga-PSMA-11 PET/CT imaging was 0.22 cm, also confirmed by MRI (range: 0.22–2.81 cm). The mean ± SD SUVmax of the BM lesions was 17.9 ± 8.6 and 6.8 ± 5.2 on ¹⁸F-FDG PET/CT and ⁶⁸Ga-PSMA-11 PET/CT imaging, respectively. Metastatic foci that could not be detected by ¹⁸F-FDG PET/CT imaging were successfully detected with ⁶⁸Ga-PSMA-11 PET/CT imaging in 11 cases (42%). The distribution and number of metastatic lesions observed on cranial MRI and ⁶⁸Ga-PSMA-11 PET/CT were compatible with each other for all patients. Immunohistochemical staining was performed in the primary tumor of 10 (38%) cases, and positive IHC staining with PSMA was detected in 5 patients. In addition, positive IHC staining with PSMA was detected in all of the four surgically excised brain metastatic tumor foci. Conclusions: In this study,⁶⁸Ga-PSMA-11 PET/CT appears to be superior to ¹⁸F-FDG in detecting BM from various tumors, largely due to its high expression associated with neovascularization and the absence of PSMA expression in normal brain parenchyma. This lack of physiological uptake in healthy brain tissue provides excellent tumor-to-background contrast, further supporting the advantage of ⁶⁸Ga-PSMA-11 over ¹⁸F-FDG for BM imaging. However, larger studies are required to confirm these findings, particularly through comparisons across tumor types and histopathological subgroups, integrating PSMA immunohistochemistry (IHC) scores with ⁶⁸Ga-PSMA-11 uptake levels. Beyond its diagnostic potential, our results may also inform PSMA-targeted therapeutic strategies, offering new perspectives for the management of patients with brain metastases from diverse primary tumors. Full article

(This article belongs to the Special Issue Hybrid Molecular Imaging Approaches in Cancer: PET/CT, PET/MRI, and Beyond)

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