Physicians

Peptides

Background

The pretargeting methods jointly developed with IBC Pharmaceuticals, Inc., are producing very high tumor/normal tissue ratios. As a result, we have been working on creating a new class of diagnostic imaging agents using both traditional gamma-emitting isotopes, such as Technetium-99m (Tc-99m), and positron-emitting isotopes, such as Fluorine-18 (F-18) and Gallium-68 (Ga-68). In 2008, we developed a rapid and facile method for the radiolabeling of peptides with F-18 via a conjugate with aluminum or other metals, and published the results in the June, 2009, issue of The Journal of Nuclear Medicine. The method has since been successfully applied to bispecific antibody pretargeting studies in animals injected with human colorectal cancer. Moreover, at the 2009 annual meeting of the Society of Nuclear Medicine, using the new labeling method, F-18 labeled peptides were shown to be stable enough to produce exceptional positron-emission tomography (PET) images of receptor-expressing tumors in animals.

PET is one of the most prominent imaging tools in diagnostic medicine. F-18 is a positron-emitting radioisotope usually given to patients as F-18 fluoro-2-deoxyglucose (F-18 FDG), a sugar analog. Increased glucose metabolism, which leads to higher uptake of F-18 FDG, is the premise of F-18 FDG PET imaging. F-18 FDG is the most widely used radiopharmaceutical in PET to determine abnormal glucose metabolism. In the United States, F-18 FDG has been approved for use in detecting certain tumors, coronary artery disease, and epilepsy. However, F-18 FDG uptake is also enhanced during inflammatory processes and in rapidly-proliferating normal cells (such as bone marrow), which may lead to false-positive results and lower specificity.

Our novel method for attaching F-18 to peptides is now protected by two new patents in the United States. Our goal is to improve the labeling process to the point where we will be capable of radiolabeling these peptides at clinical scale using single-vial kits. In related work, similar synthetic methods have also been used to prepare peptides that can be radiolabeled with Tc-99m, Ga-68, Indium-111, Lutetium-177 and Yttrium-90, which are being applied to the bispecific pretargeting technology.

References
  1. 18F labeling of a peptide for PET imaging of receptor-expressing tumors. H. Karacay, W. J. McBride, R. M. Sharkey, T. Cardillo, C. J. Smith, D. M. Goldenberg. Proc. Soc. Nucl. Med. 56th Annual Meeting, J. Nucl. Med. 50(Suppl 2): 318P (Abstr. #1567), 2009.

  2. Pretargeted immunoPET for imaging colorectal cancer in a mouse model. Proc. Soc. Nucl. Med. 56th Annual Meeting, R. Schoffelen, R. M. Sharkey, W. J. McBride, G. Franssen, A. Eek, P. Laverman, W. T. van der Graaf, W. J. Oyen, D. M. Goldenberg, O. C. Boerman. J. Nucl. Med. 50(Suppl 2): 100P (Abstr. #381), 2009.

  3. A novel method of radiolabeling peptides with aluminium-fluoride-18 (AlF-18) using various NOTA derivatives. Proc. Soc. Nucl. Med. 56th Annual Meeting, W. J. McBride, C. A. D’Souza, R. M. Sharkey, H. Karacay, E. A. Rossi, C. H. Chang, D. M. Goldenberg. J. Nucl. Med. 50(Suppl 2): 52P (Abstr. #202), 2009.

  4. A novel method of 18F radiolabeling for PET. W. J. McBride, R. M. Sharkey, H. Karacay, C. A. D'Souza, E. A. Rossi, P. Laverman, C. H. Chang, O. C. Boerman, D. M. Goldenberg. J Nucl Med. 50(6): 991-8, 2009.


Immunomedics - Physicians