Biodistribution Assessment of a Novel <sup>68</sup>Ga-Labeled Radiopharmaceutical in a Cancer Overexpressing CCK2R Mouse Model: Conventional and Radiomics Methods for Analysis
Anna Maria Pavone,
Viviana Benfante,
Paolo Giaccone,
Alessandro Stefano,
Filippo Torrisi,
Vincenzo Russo,
Davide Serafini,
Selene Richiusa,
Marco Pometti,
Fabrizio Scopelliti,
Massimo Ippolito,
Antonino Giulio Giannone,
Daniela Cabibi,
Mattia Asti,
Elisa Vettorato,
Luca Morselli,
Mario Merone,
Marcello Lunardon,
Alberto Andrighetto,
Antonino Tuttolomondo,
Francesco Paolo Cammarata,
Marco Verona,
Giovanni Marzaro,
Francesca Mastrotto,
Rosalba Parenti,
Giorgio Russo,
Albert Comelli
Affiliations
Anna Maria Pavone
Section of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Viviana Benfante
Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy
Paolo Giaccone
Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy
Alessandro Stefano
Institute of Molecular Bioimaging and Physiology, National Research Council, IBFM-CNR, 90015 Cefalù, Italy
Filippo Torrisi
Medicine and Surgery Department, University of Enna “Kore”, 94019 Enna, Italy
Vincenzo Russo
Section of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Davide Serafini
Legnaro National Laboratories, Italian Institute of Nuclear Physics, Viale Dell’Università 2, 35020 Padova, Italy
Selene Richiusa
Institute of Molecular Bioimaging and Physiology, National Research Council, IBFM-CNR, 90015 Cefalù, Italy
Marco Pometti
Nuclear Medicine Department, Cannizzaro Hospital, 95126 Catania, Italy
Fabrizio Scopelliti
Nuclear Medicine Department, Cannizzaro Hospital, 95126 Catania, Italy
Massimo Ippolito
Nuclear Medicine Department, Cannizzaro Hospital, 95126 Catania, Italy
Antonino Giulio Giannone
Pathologic Anatomy Unit, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy
Daniela Cabibi
Pathologic Anatomy Unit, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy
Mattia Asti
Radiopharmaceutical Chemistry Section, Nuclear Medicine Unit, AUSL-IRCCS di Reggio Emilia, Viale Risorgimento 80, 42122 Reggio Emilia, Italy
Elisa Vettorato
Department of Pharmaceutical Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy
Luca Morselli
Legnaro National Laboratories, Italian Institute of Nuclear Physics, Viale Dell’Università 2, 35020 Padova, Italy
Mario Merone
Research Unit of Computer Systems and Bioinformatics, Department of Engineering, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, Italy
Marcello Lunardon
Department of Physics and Astronomy, University of Padova, Via Marzolo 8, 35131 Padova, Italy
Alberto Andrighetto
Legnaro National Laboratories, Italian Institute of Nuclear Physics, Viale Dell’Università 2, 35020 Padova, Italy
Antonino Tuttolomondo
Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Molecular and Clinical Medicine, University of Palermo, 90127 Palermo, Italy
Francesco Paolo Cammarata
Institute of Molecular Bioimaging and Physiology, National Research Council, IBFM-CNR, 90015 Cefalù, Italy
Marco Verona
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
Giovanni Marzaro
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
Francesca Mastrotto
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
Rosalba Parenti
Section of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
Giorgio Russo
Institute of Molecular Bioimaging and Physiology, National Research Council, IBFM-CNR, 90015 Cefalù, Italy
Albert Comelli
Ri.MED Foundation, Via Bandiera 11, 90133 Palermo, Italy
The aim of the present study consists of the evaluation of the biodistribution of a novel 68Ga-labeled radiopharmaceutical, [68Ga]Ga-NODAGA-Z360, injected into Balb/c nude mice through histopathological analysis on bioptic samples and radiomics analysis of positron emission tomography/computed tomography (PET/CT) images. The 68Ga-labeled radiopharmaceutical was designed to specifically bind to the cholecystokinin receptor (CCK2R). This receptor, naturally present in healthy tissues such as the stomach, is a biomarker for numerous tumors when overexpressed. In this experiment, Balb/c nude mice were xenografted with a human epidermoid carcinoma A431 cell line (A431 WT) and overexpressing CCK2R (A431 CCK2R+), while controls received a wild-type cell line. PET images were processed, segmented after atlas-based co-registration and, consequently, 112 radiomics features were extracted for each investigated organ / tissue. To confirm the histopathology at the tissue level and correlate it with the degree of PET uptake, the studies were supported by digital pathology. As a result of the analyses, the differences in radiomics features in different body districts confirmed the correct targeting of the radiopharmaceutical. In preclinical imaging, the methodology confirms the importance of a decision-support system based on artificial intelligence algorithms for the assessment of radiopharmaceutical biodistribution.
