B Frigerio1, S Morlino2, E Luison1, E Seregni3, A Lorenzoni3, A Satta1, R Valdagni2,4, A Bogni3, C Chiesa3, M Mira3,5, S Canevari6, A Alessi3, M Figini7. 1. Biomarkers Unit, Department of Applied Research and Technical Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 2. Radiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 3. Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 4. Department of Oncology and Hemato-oncology, University of Milan, Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 5. Present address: Fisica Sanitaria - ASST Ovest Milanese, Via Papa Giovanni Paolo II, Legnano, Milan, Italy. 6. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 7. Biomarkers Unit, Department of Applied Research and Technical Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. mariangela.figini@istitutotumori.mi.it.
Abstract
BACKGROUND: Prostate cancer (PCa) is the second leading cause of cancer-related death in the Western population. The use in oncology of positron emission tomography/computed tomography (PET/CT) with emerging radiopharmaceuticals promises accurate staging of primary disease, restaging of recurrent disease and detection of metastatic lesions. Prostate-specific membrane antigen (PSMA) expression, directly related to androgen-independence, metastasis and progression, renders this tumour associate antigen a good target for the development of new radiopharmaceuticals for PET. Aim of this study was to demonstrate in a preclinical in vivo model (PSMA-positive versus PSMA-negative tumours) the targeting specificity and sensitivity of the anti-PSMA single-chain variable fragment (scFv) labelled with 124I. METHODS: The 124I-labeling conditions of the antibody fragment scFvD2B were optimized and assessed for purity and immunoreactivity. The specificity of 124I-scFvD2B was tested in mice bearing PSMA-positive and PSMA-negative tumours to assess both ex-vivo biodistribution and immune-PET. RESULTS: The uptake fraction of 124I-scFvD2B was very high on PSMA positive cells (range 75-91%) and highly specific and immuno-PET at the optimal time point, defined between 15 h and 24 h, provides a specific localization of lesions bearing the target antigen of interest (PSMA positive vs PSMA negative tumors %ID/g: p = 0.0198 and p = 0.0176 respectively) yielding a median target/background ratio around 30-40. CONCLUSIONS: Preclinical in vivo results of our immuno-PET reagent are highly promising. The target to background ratio is improved notably using PET compared to SPECT previously performed. These data suggest that, upon clinical confirmation of sensitivity and specificity, our anti-PSMA 124I-scFvD2B may be superior to other diagnostic modalities for PCa. The possibility to combine in patients our 124I-scFvD2B in multi-modal systems, such as PET/CT, PET/MR and PET/SPECT/CT, will provide quantitative 3D tomographic images improving the knowledge of cancer biology and treatment.
BACKGROUND:Prostate cancer (PCa) is the second leading cause of cancer-related death in the Western population. The use in oncology of positron emission tomography/computed tomography (PET/CT) with emerging radiopharmaceuticals promises accurate staging of primary disease, restaging of recurrent disease and detection of metastatic lesions. Prostate-specific membrane antigen (PSMA) expression, directly related to androgen-independence, metastasis and progression, renders this tumour associate antigen a good target for the development of new radiopharmaceuticals for PET. Aim of this study was to demonstrate in a preclinical in vivo model (PSMA-positive versus PSMA-negative tumours) the targeting specificity and sensitivity of the anti-PSMA single-chain variable fragment (scFv) labelled with 124I. METHODS: The 124I-labeling conditions of the antibody fragment scFvD2B were optimized and assessed for purity and immunoreactivity. The specificity of 124I-scFvD2B was tested in mice bearing PSMA-positive and PSMA-negative tumours to assess both ex-vivo biodistribution and immune-PET. RESULTS: The uptake fraction of 124I-scFvD2B was very high on PSMA positive cells (range 75-91%) and highly specific and immuno-PET at the optimal time point, defined between 15 h and 24 h, provides a specific localization of lesions bearing the target antigen of interest (PSMA positive vs PSMA negative tumors %ID/g: p = 0.0198 and p = 0.0176 respectively) yielding a median target/background ratio around 30-40. CONCLUSIONS: Preclinical in vivo results of our immuno-PET reagent are highly promising. The target to background ratio is improved notably using PET compared to SPECT previously performed. These data suggest that, upon clinical confirmation of sensitivity and specificity, our anti-PSMA124I-scFvD2B may be superior to other diagnostic modalities for PCa. The possibility to combine in patients our 124I-scFvD2B in multi-modal systems, such as PET/CT, PET/MR and PET/SPECT/CT, will provide quantitative 3D tomographic images improving the knowledge of cancer biology and treatment.
Authors: George Crișan; Nastasia Sanda Moldovean-Cioroianu; Diana-Gabriela Timaru; Gabriel Andrieș; Călin Căinap; Vasile Chiș Journal: Int J Mol Sci Date: 2022-04-30 Impact factor: 6.208
Authors: Zora Novakova; Nikola Belousova; Catherine A Foss; Barbora Havlinova; Marketa Gresova; Gargi Das; Ala Lisok; Adam Prada; Marketa Barinkova; Martin Hubalek; Martin G Pomper; Cyril Barinka Journal: Int J Mol Sci Date: 2020-09-12 Impact factor: 5.923