Nabeel Nabulsi PhD
Associate Research Scientist in Diagnostic Radiology; Chief Quality Control and Regulatory Affairs
Positron Emission Tomography (PET) Radiopharmaceuticals
My interests in PET embrace both Chemistry and Imaging
Extensive Research Description
As a radiochemist, I find rewarding the development of facile synthetic methodologies for the preparation of radiopharmaceuticals which incorporate the short half-life C-11 and F-18 radionuclides that are frequently employed for PET imaging. In particular, synthesis of C-11 radiopharmaceuticals is very challenging in that it generally has to be accomplished inside 60 minutes in order to possess adequate radioactivity for PET imaging. Improving overall binding properties of existing radioligands and the development of new ligands comprise my imaging interest in the areas of CNS and oncology. For CNS, I am interested in developing radiopharmaceuticals that can be employed for early diagnosis of Alzheimer and Parkinson diseases and which can lead to development of better treatments. Another interesting area, FAAH (fatty acid amide hydrolase) has emerged as a novel therapeutic target for a range of clinical disorders. It is a membrane-bound intracellular serine hydrolase that is responsible for AEA (Anandamide, an endogenous cannabinoid) metabolism. Indeed, FAAH has been targeted as biomarker of AEA which is known to modulate several physiological processes in both peripheral and nervous system. FAAH inactivation produces proactive subset of behavioral effects similar to that observed for direct CB1 agonists, but without inducing analogous side-effects. To date, all evidence suggests that compounds which increase the tone of AEA, whether blocking its transport or inhibiting its metabolism, are therapeutically valuable for treatment. Accordingly imaging FAAH should accelerate validation of FAAH inhibitors as therapeutic targets. Small-molecule radiotracers not only would provide valuable research tools for further understanding of this and other therapeutic targets, but also allows fast validation of efficacy and selectivity of potential drug inhibitors as well. The potential disorders which can benefit from targeted enhancement of AEA include analgesic, anti tumor and neuroprotection. Regarding oncology, there is a dire need for radiotracers which are capable of early detection of pancreatic cancer. It is the second most common gastrointestinal malignancy in the USA. Meanwhile, peptide transporters are important drug delivery targets and growing number of studies have been reported on regulation of their transport capacity. Tumor cells have been shown to up-regulate the expression of the peptide transporter type PepT1, and high levels of this transporter have been found in variety of cancer cells, including pancreatic. Thus, increased expression of PepT1 in the cellular membrane of cancer cells has been investigated as a possible target for delivery of peptidomimetic anti-cancer drugs as well as prodrugs. Bestatin, a leukotriene A4 hydrolase inhibitor, is among the peptidomimetic PepT1 substrates which have been shown to have anticancer activity towards non-lymphocytic leukemia as well as pancreatic adenocarcinoma. In this regard, I am interested in developing radiotracers that are substrates of the peptide transporter PepT1 for imaging pancreatic cancer. Alternatively, inhibition of PepT1 activity has also been suggested as a novel chemotherapy approach. With this in mind, radiotracers that are substrates for PepT1 should also facilitate the development of PepT1 inhibitors.