In vivo immuno-PET imaging of thyroid tumor nodules using Galectin-3 as tumor marker - Revised version

• Applicant: Privatdozent Calogero D`Alessandria, Ph.D.
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology ; Biochemistry
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 271159865

Despite a high prevalence of thyroid nodules in the adult population, conventional thyroid scintigraphy using radioiodine does not allow the distinction between benign and malignant proliferation. Immunohistochemical and molecular analysis of biopsy specimens has provided strong evidence for galectin3 as thyroid cancer marker, and we have obtained preliminary experimental evidence about visualization of galectin3 expression in mouse models of thyroid tumour by immunoimaging. In the present project, we aim to further develop radio-immunoconjugates for immunoPET imaging of galectin3. To take advantage of the better tissue penetration and faster plasma clearance compared with full-size antibodies, we plan to develop recombinant Fab fragments derived from existing galectin3 specific mAbs and radiolabel them with zirconium89. The V genes will be cloned from hybridoma cell lines and the Fab fragments functionally expressed in E. coli, if necessary followed by optimization via protein engineering. Resulting human chimeric Fab fragments with high affinity toward galectin3 will be coupled to metal specific chelator compounds, both randomly via conjugation to Lys side chains and in a site directed fashion utilizing novel chemistries, and radiolabelled with the PET isotopes. The radio-immunoconjugates will be subjected to in vitro characterization and in vivo imaging in mice that carry different thyroid subcutaneous and orthotopic xenograft tumors. This approach may allow, in the future, the preoperative discrimination between benign and malignant thyroid nodules, leading to better patient selection and therapy decision, eventually reducing the number of unnecessary thyroid surgical treatments.

• DFG Programme: Research Grants
• International Connection: Italy
• Co-Investigators: Professorin Dr. Irene Esposito; Privatdozent Dr. Michael Kuhlmann; Dr. Alfred Morgenstern; Privatdozentin Dr. Angela M. Otto; Professor Dr. Markus Schwaiger; Professor Arne Skerra, Ph.D.; Privatdozent Dr. Gregor Weirich
• Cooperation Partner: Professor Armando Bartolazzi, Ph.D.