Team 2: Nuclear Oncology

Team 2 Leaders : Pr. Michel Chérel & Pr Françoise Kraeber-Bodéré

Our research aims to develop diagnostic and therapeutic tools to fight cancer by focusing on the delivery of radionuclides to cancer cells and their biological effects.

Fundings/Networks

Platforms

• Lugat, A., et al. Survival impact of [²²⁵Ac]Ac-DOTATOC alpha-therapy in a preclinical model of pancreatic neuroendocrine tumor liver micrometastases. Eur J Nucl Med Mol Imaging (2024). https://doi.org/10.1007/s00259-024-06918-0
• Ludovic Le Saux et al. Sydnone-based prosthetic groups for radioiodination, Bioorg. Med. Chem. (2024). https://doi.org/10.1016/j.bmc.2024.117904.
• Loris Roncali, et al. Brain intratumoural astatine-211 radiotherapy targeting syndecan-1 leads to durable glioblastoma remission and immune memory in female mice, eBioMedicine (2024). https://doi.org/10.1016/j.ebiom.2024.105202.

• Please click on this link to see selected publications

With the identification of numerous relevant biomarkers, nuclear medicine offers innovative approaches for precision therapeutics and theranostics in oncology, using radiolabeled antibodies or other vectors. Our team gathers working groups with all the competences required to design new radiopharmaceuticals and validate them from preclinical to clinical evaluations, especially immuno-PET and targeted radionuclide therapy (TRT), especially using alpha emitters. This translational research requires a pluridisciplinary expertise going from the extraction of the radionuclides to the preparation of the radiopharmaceuticals.

Originally investigating radiolabeled antibodies to treat cancer and hemopathies, over the past 5 years we have been moving forward to developing a research in molecular imaging, especially PET, innovative PET emitters being now available for imaging tumor phenotype, in particular with radiolabeled mAbs (immuno-PET) through theranostic approaches. Biomarker imaging using immuno-PET represents also a promising tool to predict efficacy of targeted therapies (precision therapeutics based on predictive imaging or companion diagnostic) or to predict patient outcome (prognostic imaging and radiomics). Development of radiopharmaceuticals relies on a fundamental and forward thinking on radionuclides, targets, new vectors and requires to develop pertinent animal models (murine, canine) before clinical development, but also requires expertise in quantitative imaging. Each specific field including radiopharmacy, chemistry/radiochemistry, radiobiology and immunology is developing its own work and projects towards a common goal. Our pluridisciplinary research is integrated in the personalized/stratified medicine, tumor targeting with innovative α, β- and β+ radionuclides allowing a predictive whole-body imaging which is complementary to metabolic (PET using FDG) and morphologic (CT and MRI) imaging as well as image guided innovative targeted therapies (quantitative imaging, dosimetry, radiomics).

• Vanermen, M. et al. Astatine-211 radiolabelling chemistry: from basics to advanced biological applications. EJNMMI radiopharm. chem. (2024). https://doi.org/10.1186/s41181-024-00298-4
• Lugat, A., et al. Survival impact of [²²⁵Ac]Ac-DOTATOC alpha-therapy in a preclinical model of pancreatic neuroendocrine tumor liver micrometastases. Eur J Nucl Med Mol Imaging (2024). https://doi.org/10.1007/s00259-024-06918-0
• Ludovic Le Saux et al. Sydnone-based prosthetic groups for radioiodination, Bioorg. Med. Chem. (2024). https://doi.org/10.1016/j.bmc.2024.117904.
• Loris Roncali, et al. Brain intratumoural astatine-211 radiotherapy targeting syndecan-1 leads to durable glioblastoma remission and immune memory in female mice, eBioMedicine (2024). https://doi.org/10.1016/j.ebiom.2024.105202.
• Métivier C., et al. Preclinical Evaluation of a ⁶⁴Cu-Based Theranostic Approach in a Murine Model of Multiple Myeloma. Pharmaceutics. 2023, 15(7), 1817; https://doi.org/10.3390/pharmaceutics15071817 
• Perrin J, Capitao M, Allard M , Chouin N , Gouard S, Marionneau-Lambot S, Louvet C, Donnadieu E, Bruchertseifer F, Morgenstern A, Chérel M, Gaschet J, Guilloux Y. Targeted alpha particle therapy remodels the tumor microenvironment and improves efficacy of immunotherapy. Int J Radiat Oncol Biol Phys. 2022;112(3):790-801. doi: 10.1016/j.ijrobp.2021.10.013.
• Maingueneau C, Berdal M, Eychenne R, Gaschet J, Chérel M, Gestin JF, Guérard F. ²¹¹At and ¹²⁵I-Labeling of (Hetero)Aryliodonium Ylides: Astatine Wins Again. Chemistry. 2022;28(11):e202104169. doi: 10.1002/chem.202104169.
• Alberge JB, Kraeber-Bodéré F, Jamet B, Touzeau C, Caillon H, Wuilleme S, Avet-Loiseau H, Corre J, Magrangeas F, Carlier T, Bodet-Milin C, Chérel M, Moreau P, Minvielle S, Bailly C. Molecular signature of FDG-PET biomarkers in newly diagnosed multiple myeloma patients: a genome-wide transcriptome analysis from the CASSIOPET study. J Nucl Med. 2022 Jan 27:jnumed.121.262884. doi: 10.2967/jnumed.121.262884. [Online ahead of print]
• Delage JA, Gnesin S, Prior JO, Barbet J, Le Saëc P, Marionneau-Lambot S, Gouard S, Chérel M, Bourgeois M, Schaefer N, Viertl D, Fierle JK, Dunn SM, Faivre-Chauvet A. Copper-64-Labeled 1C1m-Fc, a New Tool for TEM-1 PET Imaging and Prediction of Lutetium-177-Labeled 1C1m-Fc Therapy Efficacy and Safety. Cancers. 2021;13(23):5936. doi: 10.3390/cancers13235936.
• Bodet-Milin C, Faivre-Chauvet A, Carlier T, Ansquer C, Rauscher A, Frampas E, Toulgoat F, Masson D, Bourgeois M, Cerato E, Rohmer V, Couturier O, Drui D, Goldenberg DM, Sharkey RM, Barbet J, Kraeber-Bodere F. Anti-CEA pretargeted Immuno-PET shows higher sensitivity than DOPA-PET/CT to detect relapsing metastatic medullary thyroid carcinoma: Post- hoc analysis of the iPET-MTC study. J Nucl Med. 2021;62(9):1221-1227. doi: 10.2967/jnumed.120.252791.
• Guérard F, Maingueneau C, Liu L, Eychenne R, Gestin JF, Montavon G, and Galland N. Advances in the Chemistry of Astatine and Implications for the Development of Radiopharmaceuticals. Acc. Chem. Res. 2021, 54, 3264−3275. doi: 10.1021/acs.accounts.1c00327.
• Jamet B, Morvan L, Nanni C, Michaud AV, Bailly C, Chauvie S, Moreau P, Touzeau C, Zamagni E, Bodet-Milin C, Kraeber-Bodéré F, Mateus D, Carlier T. Random survival forest to predict transplant-eligible newly diagnosed multiple myeloma outcome including FDG-PET radiomics: a combined analysis of two independent prospective European trials. Eur J Nucl Med Mol Imaging. 2021;48(4):1005-1015. doi: 10.1007/s00259-020-05049-6.
• Capitao M, Perrin J, Simon S, Gouard S, Chouin N, Bruchertseifer F, Morgenstern A, Rbah‐Vidal L, Chérel M, Scotet E, Labarrière N, Guilloux Y and Gaschet J. Anti‐Tumor Efficacy of PD‐L1 Targeted Alpha‐Particle Therapy in a Human Melanoma Xenograft Model. Cancers. 2021;13(6):1256. doi: 10.3390/cancers13061256.
• Touchefeu Y, Bailly C, Frampas E, Eugène T, Rousseau C, Bourgeois M, Bossard C, Faivre-Chauvet A, Rauscher A, Masson D, David A, Cerato E, Carlier T, Sharkey RM, Goldenberg DM, Barbet J, Kraeber-Bodere F, Bodet-Milin C. Promising clinical performance of pretargeted immuno-PET with anti-CEA bispecific antibody and gallium-68-labelled IMP-288 peptide for imaging colorectal cancer metastases: a pilot study. Eur J Nucl Med Mol Imaging. 2021;48(3):874-882. doi: 10.1007/s00259-020-04989-3.
• Berdal M, Gouard S, Eychenne R, Marionneau-Lambot S, Croyal M, Faivre-Chauvet A, Chérel M, Gaschet J, Gestin JF and Guérard F. Investigation on the reactivity of nucleophilic radiohalogens with arylboronic acids in water: access to an efficient single-step method for the radioiodination and astatination of antibodies. Chem. Sci. 2021;12(4):1458. DOI: 10.1039/d0sc05191h.
• Grémy O, Mougin-Degraef M, Devilliers K, Berdal M, Laroche P, Miccoli L.  DTPA-Coated Liposomes as a New Delivery Vehicle for Plutonium Decorporation.  Radiat Res 2021;195(1):77-92.  doi: 10.1667/RADE-20-00142.1.
• Zamagni E, Nanni C, Dozza L, Carlier T, Bailly C, Tacchetti P, Versari A, Chauvie S, Gallamini A, Gamberi B, Caillot D, Patriarca F, Macro M, Boccadoro M, Garderet L, Barbato S, Fanti S, Perrot A, Gay F, Sonneveld P, Karlin L, Cavo M, Bodet-Milin C, Moreau P, Kraeber-Bodéré F. Standardization of 18F-FDG-PET/CT According to Deauville Criteria for Metabolic Complete Response Definition in Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2021;39(2):116-125. doi: 10.1200/JCO.20.00386.
• Millardet M, Moussaoui S, Mateus D, Idier J, Carlier T. Local-mean preserving post-processing step for non-negativity enforcement in PET imaging: application to 90Y-PET. IEEE Trans Med Imaging. 2020;39(11):3725-3736. doi: 10.1109/TMI.2020.3003428.
• Gouard S, Maurel C, Marionneau-Lambot S , Dansette D, Bailly C, Guérard F, Chouin N, Haddad F, Alliot C, Gaschet J, Eychenne R, Kraeber-Bodéré F and Chérel M. Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease. Cancers 2020; 12, 2721; doi:10.3390/cancers12092721.
• Ansquer C, Drui D, Mirallié E, Renaudin-Autain K, Denis A, Gimenez-Roqueplo AP, Leux C, Toulgoat F, Kraeber-Bodéré F, Carlier T. Usefulness of FDG-PET/CT-Based Radiomics for the Characterization and Genetic Orientation of Pheochromocytomas Before Surgery. Cancers. 2020;12(9):E2424. doi: 10.3390/cancers12092424.
• Touchefeu Y, Bailly C, Frampas E, Eugène T, Rousseau C, Bourgeois M, Bossard C, Faivre-Chauvet A, Rauscher A, Masson D, David A, Cerato E, Carlier T, Sharkey RM, Goldenberg DM, Barbet J, Kraeber-Bodéré F, Bodet-Milin C. Promising clinical performance of pretargeted immuno-PET with anti-CEA bispecific antibody and gallium-68-labelled IMP-288 peptide for imaging colorectal cancer metastases: a pilot study. Eur J Nucl Med Mol Imaging. 2020;48:874. doi: 10.1007/s00259-020-04989-3.