Francesco Fiz1, Gianluca Bottoni2, Martina Ugolini2, Sergio Righi3, Alessio Cirone3, Maria Carmen Garganese4, Antonio Verrico5, Andrea Rossi6,7, Claudia Milanaccio5, Antonia Ramaglia6, Angela Mastronuzzi8, Massimo Eraldo Abate9, Antonella Cacchione8, Carlo Gandolfo10, Giovanna Stefania Colafati10, Maria Luisa Garrè5, Giovanni Morana11, Arnoldo Piccardo2. 1. Department of Nuclear Medicine, E.O. Ospedali Galliera, Galliera Hospital, Mura delle Cappuccine 14, 16128, Genoa, Italy. francesco.fiz.nm@gmail.com. 2. Department of Nuclear Medicine, E.O. Ospedali Galliera, Galliera Hospital, Mura delle Cappuccine 14, 16128, Genoa, Italy. 3. Medical Physics Department, E.O. Galliera Hospital, Genoa, Italy. 4. Nuclear Medicine Unit/Imaging Department, IRCCS Bambino Gesù Children's Hospital, Rome, Italy. 5. Neuro-Oncology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 6. Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy. 7. Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy. 8. Neuro-Oncology Unit, Department of Paediatric Haematology/Oncology, Cell Therapy, Gene Therapies and Hemopoietic Transplant, Bambino Gesù Children's Hospital, IRCCS, 00165, Rome, Italy. 9. Pediatric Oncology Unit, AORN Santobono-Pausilipon Hospital, Naples, Italy. 10. Imaging Department, Neuroradiology Unit, IRCCS Bambino Gesù Children's Hospital, Rome, Italy. 11. Department of Neurosciences, University of Turin, Turin, Italy.
Abstract
PURPOSE OF THE REPORT: Paediatric diffuse high-grade gliomas (PDHGG) are rare central nervous system neoplasms lacking effective therapeutic options. Molecular imaging of tumour metabolism might identify novel diagnostic/therapeutic targets. In this study, we evaluated the distribution and the dosimetry aspects of [64Cu]CuCl2 in PDHGG subjects, as copper is a key element in cellular metabolism whose turnover may be increased in tumour cells. MATERIAL AND METHODS: Paediatric patients with PDHGG were prospectively recruited. [64Cu]CuCl2 PET/CT was performed 1 h after tracer injection; if the scan was positive, it was repeated 24 and 72 h later. Lesion standardised uptake value (SUV) and target-to-background ratio (TBR) were calculated. Tumour and organ dosimetry were computed using the MIRD algorithm. Each patient underwent an MRI scan, including FLAIR, T2-weighted and post-contrast T1-weighted imaging. RESULTS: Ten patients were enrolled (median age 9, range 6-16 years, 6 females). Diagnoses were diffuse midline gliomas (n = 8, 5 of which with H3K27 alterations) and diffuse hemispheric gliomas (n = 2). Six patients had visible tracer uptake (SUV: 1.0 ± 0.6 TBR: 5 ± 3.1). [64Cu]CuCl2 accumulation was always concordant with MRI contrast enhancement and was higher in the presence of radiological signs of necrosis. SUV and TBR progressively increased on the 24- and 72-h acquisitions (p < 0.05 and p < 0.01, respectively). The liver and the abdominal organs received the highest non-target dose. CONCLUSIONS: [64Cu]CuCl2 is a well-tolerated radiotracer with reasonably favourable dosimetric properties, showing selective uptake in tumour areas with visible contrast enhancement and necrosis, thus suggesting that blood-brain barrier damage is a pre-requisite for its distribution to the intracranial structures. Moreover, tracer uptake showed an accumulating trend over time. These characteristics could deserve further analysis, to determine whether this radiopharmaceutical might have a possible therapeutic role as well.
PURPOSE OF THE REPORT: Paediatric diffuse high-grade gliomas (PDHGG) are rare central nervous system neoplasms lacking effective therapeutic options. Molecular imaging of tumour metabolism might identify novel diagnostic/therapeutic targets. In this study, we evaluated the distribution and the dosimetry aspects of [64Cu]CuCl2 in PDHGG subjects, as copper is a key element in cellular metabolism whose turnover may be increased in tumour cells. MATERIAL AND METHODS: Paediatric patients with PDHGG were prospectively recruited. [64Cu]CuCl2 PET/CT was performed 1 h after tracer injection; if the scan was positive, it was repeated 24 and 72 h later. Lesion standardised uptake value (SUV) and target-to-background ratio (TBR) were calculated. Tumour and organ dosimetry were computed using the MIRD algorithm. Each patient underwent an MRI scan, including FLAIR, T2-weighted and post-contrast T1-weighted imaging. RESULTS: Ten patients were enrolled (median age 9, range 6-16 years, 6 females). Diagnoses were diffuse midline gliomas (n = 8, 5 of which with H3K27 alterations) and diffuse hemispheric gliomas (n = 2). Six patients had visible tracer uptake (SUV: 1.0 ± 0.6 TBR: 5 ± 3.1). [64Cu]CuCl2 accumulation was always concordant with MRI contrast enhancement and was higher in the presence of radiological signs of necrosis. SUV and TBR progressively increased on the 24- and 72-h acquisitions (p < 0.05 and p < 0.01, respectively). The liver and the abdominal organs received the highest non-target dose. CONCLUSIONS: [64Cu]CuCl2 is a well-tolerated radiotracer with reasonably favourable dosimetric properties, showing selective uptake in tumour areas with visible contrast enhancement and necrosis, thus suggesting that blood-brain barrier damage is a pre-requisite for its distribution to the intracranial structures. Moreover, tracer uptake showed an accumulating trend over time. These characteristics could deserve further analysis, to determine whether this radiopharmaceutical might have a possible therapeutic role as well.
Authors: O Boudaouara; S Charfi; M Bahri; J Daoud; M Z Boudawara; N Gouiaa; T Sellami Boudawara Journal: Neurochirurgie Date: 2019-03-29 Impact factor: 1.553
Authors: Gil Covarrubias; Mette L Johansen; Jason Vincent; Bernadette O Erokwu; Sonya E L Craig; Abdelrahman Rahmy; Anthony Cha; Morgan Lorkowski; Christina MacAskill; Bryan Scott; Madhusudhana Gargesha; Debashish Roy; Chris A Flask; Efstathios Karathanasis; Susann M Brady-Kalnay Journal: Nanomedicine Date: 2020-05-13 Impact factor: 5.307
Authors: David N Louis; Arie Perry; Pieter Wesseling; Daniel J Brat; Ian A Cree; Dominique Figarella-Branger; Cynthia Hawkins; H K Ng; Stefan M Pfister; Guido Reifenberger; Riccardo Soffietti; Andreas von Deimling; David W Ellison Journal: Neuro Oncol Date: 2021-08-02 Impact factor: 13.029