Al18F-labeling

Radiolabeled receptor binding peptides have emerged as an important class of tracers for tumor diagnosis. The specific receptor binding property of the ligand can be exploited by labeling the ligand with a radionuclide and using the radiolabeled ligand as a vehicle to guide the radioactivity to the tissues expressing a particular receptor. For peptide receptor radionuclide imaging peptides are labeled mainly with gamma emitting radionuclides In-111 and Tc-99m. To exploit the exquisite sensitivity and resolution of PET imaging the peptide could be labeled with positron emitting radionuclides such as Ga-68, F-18 and Cu-64. F-18 is the most widely used radionuclide in PET: it has ideal nuclear characteristics and is widely available. Recently, we developed a new one-step chelate-based F-18 labeling method that can be used to label peptides and other small molecules with high efficiency (Laverman et al., J Nucl Med 2010;51:454-461). This new labeling method is based on the chelation of aluminumfluoride (“AlF-18”) by NOTA. In ongoing projects we aim to optimize and further exploit this new one-step chelate-based F-18 labeling method. Focus will be on various F-18 labeled peptides (somatostatin and bombesin analogues and RGDfK) for PET imaging of neuroendocrine tumors, prostate cancer and for αvβ3 expression in tumors, respectively. Peptides will be conjugated with an optimized NOTA analogue. The effect of various linkers will be tested to further optimize the pharmacokinetic properties of the peptides. In the second part of the project, the clinical feasibility of the new F-18 labeling method will be demonstrated using one of the F-18-labeled peptides in patients.


People

Publications

  • S. Lütje, G.M. Franssen, R.M. Sharkey, P. Laverman, E.A. Rossi, D.M. Goldenberg, W.J.G. Oyen, O.C. Boerman and W.J. McBride. "Anti-CEA Antibody Fragments Labeled with [(18)F]AlF for PET Imaging of CEA-Expressing Tumors", Bioconjug Chem 2014;25:335-341. Abstract/PDF DOI PMID

  • P. Laverman, W.J. McBride, R.M. Sharkey, D.M. Goldenberg and O.C. Boerman. "Al(18) F labeling of peptides and proteins", J Labelled Comp Radiopharm 2014;57:219-223. Abstract/PDF DOI PMID

  • I. Dijkgraaf, S.Y.A. Terry, W.J. McBride, D.M. Goldenberg, P. Laverman, G.M. Franssen, W.J.G. Oyen and O.C. Boerman. "Imaging integrin alpha-v-beta-3 expression in tumors with an 18F-labeled dimeric RGD peptide", Contrast Media and Molecular Imaging 2013;8:238-245. Abstract DOI PMID

  • S. Heskamp, P. Laverman, D. Rosik, F. Boschetti, W.T.A. van der Graaf, W.J.G. Oyen, H.W.M. van Laarhoven, V. Tolmachev and O.C. Boerman. "Imaging of human epidermal growth factor receptor type 2 expression with 18F-labeled affibody molecule ZHER2:2395 in a mouse model for ovarian cancer", Journal of Nuclear Medicine 2012;53:146-153. Abstract/PDF DOI PMID

  • P. Laverman, C.A. D'Souza, A. Eek, W.J. McBride, R.M. Sharkey, W.J.G. Oyen, D.M. Goldenberg and O.C. Boerman. "Optimized labeling of NOTA-conjugated octreotide with F-18", Tumor Biology 2012;33:427-434. Abstract/PDF DOI PMID

  • P. Laverman, J.K. Sosabowski, O.C. Boerman and W.J.G. Oyen. "Radiolabelled peptides for oncological diagnosis", European Journal of Nuclear Medicine and Molecular Imaging 2012;39 Suppl 1:S78-S92. Abstract/PDF DOI PMID

  • P. Laverman, W.J. McBride, R.M. Sharkey, A. Eek, L. Joosten, W.J.G. Oyen, D.M. Goldenberg and O.C. Boerman. "A novel facile method of labeling octreotide with (18)F-fluorine", Journal of Nuclear Medicine 2010;51:454-461. Abstract/PDF DOI PMID

  • R. Schoffelen, R.M. Sharkey, D.M. Goldenberg, G. Franssen, W.J. McBride, E.A. Rossi, C.-H. Chang, P. Laverman, J.A. Disselhorst, A. Eek, W.T.A. van der Graaf, W.J.G. Oyen and O.C. Boerman. "Pretargeted immuno-positron emission tomography imaging of carcinoembryonic antigen-expressing tumors with a bispecific antibody and a 68Ga- and 18F-labeled hapten peptide in mice with human tumor xenografts", Molecular Cancer Therapeutics 2010;9:1019-1027. Abstract DOI PMID

  • W.J. McBride, R.M. Sharkey, H. Karacay, C.A. D'Souza, E.A. Rossi, P. Laverman, C.-H. Chang, O.C. Boerman and D.M. Goldenberg. "A novel method of 18F radiolabeling for PET", Journal of Nuclear Medicine 2009;50:991-998. Abstract/PDF DOI PMID