The PET Radiochemistry Laboratory of NIBIB has had a productive year of research. The majority of our effort has focused on projects that are collaborations with other NIH investigators. The group presented six abstracts at the International Symposium on Radiopharmaceutical Sciences this past spring. Great strides have been made in several projects, and the successful recruitment of new group members predicts an exciting future.? ? We have continued to expand our project on the imaging of HER2 receptor in certain tumors with an extensive small animal PET imaging program. This is a collaborative project among the NIBIB PET Radiochemistry Laboratory, the group of Jacek Capala in NCI's Radiation Oncology Branch, and Affibody AG (CRADA partner of Dr. Capala). Our major contribution was the development of a manual radiosynthetic procedure for preparing an F-18 radiolabeled maleimide that will couple selectively with the lone cysteine residue in the HER2 specific Affibody. We have focused on the reproducibility of the radiolabeling sequence and have begun evaluation of procedures to enhance the stability of the radiolabeled protein. We have initiated studies of the metabolic fate of the protein. This project has been the subject of several abstracts and the submission of one manuscript to a peer reviewed journal. In addition, a provisional patent application for this technology has been submitted.? ? We have a collaborative project with the NIAID on the development of an F-18 radiolabeled nucleoside analog reverse transcriptase inhibitor. The goal is to be able to study the biodistribution of the analogous non-fluorine containing drug, tenofovir, as a function of chronic treatment. The most important validation was to demonstrate that the biodistribution of the F-18 analog and the parent drug were the same in the normal rat. We conducted an experiment where both F-18 compound and the C-14 radiolabeled parent were injected into the same animal. Four time points were selected and the data collected. The radioactivity levels were very similar in all tissues except lung and kidney. We are evaluating this to determine if the correlation is good enough to allow the desired use.? ? We have developed and validated an HPLC/MS method for the determination of ligand biodistribution at tracer doses for a 5HT1A receptor ligand previously developed in our laboratories, FP-WAY. A new, highly sensitive triple quadrapole ion trap mass spectrometer began operation in our group over the summer. We expect the sensitivity enhancements to allow us to conduct more biodistribution and metabolism studies of small molecules without the need to radiolabel the test molecules. Currently this technology is being applied to the search for new 5HT1A receptor ligands. ? ? We are initiating new collaborations with other institute investigators that we anticipate will lead to new PET radioligands to study human diseases. In the next year we expect to see dividends from these new projects.? ? Our training component was very successful. A post-doctoral fellow departed for a more permanent position at a new imaging center in Texas. We had two college level summer students conduct research in our laboratories. We have successfully recruited a new post-doctoral fellow who will begin later this calendar year.
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