Nabeel Nabulsi, PhD

Research Scientist; Deputy Director of PET Center Chemistry Section; Chief Quality Control and Regulatory Affairs

Research Departments & Organizations

Radiology & Biomedical Imaging: Bioimaging Sciences: Positron Emission Tomography (PET): PET Radioligand Development for Mental Health (PRDMH)

Research Summary

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.

Clinical Trials

Conditions Study Title
Mental Health & Behavioral Research, Tobacco Addiction Imaging Tobacco Smoking Withdrawal using [11C]PHNO
Mental Health & Behavioral Research Imaging 11B-hydroxysteroid dehydrogenase availability in vivo
Mental Health & Behavioral Research, Alzheimer's Disease Synaptic Density PET tracer evaluation
Mental Health & Behavioral Research Imaging Microglial Activation in PTSD wITH PET
Diseases of the Nervous System Imaging pancreatic beta-cells with PET neuroimaging agent 11C-PHNO
Diseases of the Nervous System, Mental Health & Behavioral Research SV2A PET Imaging in Healthy Subjects and Epilepsy Patients

Selected Publications

  • Imaging synaptic density in the living human brain.

    Finnema SJ, Nabulsi NB, Eid T, Detyniecki K, Lin SF, Chen MK, Dhaher R, Matuskey D, Baum E, Holden D, Spencer DD, Mercier J, Hannestad J, Huang Y, Carson RE. Imaging synaptic density in the living human brain. Science Translational Medicine 2016, 8:348ra96. 2016

  • Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain.

    Nabulsi N, Mercier J, Holden D, Carre S, Najafzadeh S, Vandergeten MC, Lin SF, Deo AK, Price N, Wood M, Lara-Jaime T, Montel F, Laruelle M, Carson RE, Hannestad J, Huang Y. Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain. Journal Of Nuclear Medicine : Official Publication, Society Of Nuclear Medicine 2016, 57:777-84. 2016

  • [11C]GR103545: novel one-pot radiosynthesis with high specific activity.

    Nabulsi NB, Zheng MQ, Ropchan J, Labaree D, Ding YS, Blumberg L, Huang Y. [11C]GR103545: novel one-pot radiosynthesis with high specific activity. Nuclear Medicine And Biology 2011, 38:215-21. 2011

  • High-resolution imaging of brain 5-HT 1B receptors in the rhesus monkey using [11C]P943.

    Nabulsi N, Huang Y, Weinzimmer D, Ropchan J, Frost JJ, McCarthy T, Carson RE, Ding YS. High-resolution imaging of brain 5-HT 1B receptors in the rhesus monkey using [11C]P943. Nuclear Medicine And Biology 2010, 37:205-14. 2010

  • [11C]Glycylsarcosine: synthesis and in vivo evaluation as a PET tracer of PepT2 transporter function in kidney of PepT2 null and wild-type mice.

    Nabulsi NB, Smith DE, Kilbourn MR. [11C]Glycylsarcosine: synthesis and in vivo evaluation as a PET tracer of PepT2 transporter function in kidney of PepT2 null and wild-type mice. Bioorganic & Medicinal Chemistry 2005, 13:2993-3001. 2005

  • TARGETING PEPT1 FOR DETECTING PANCREAS CANCER WITH [11C]GLY-SAR: MICROPET IMAGING OF NUDE MICE BEARING ASPC-1, CAPAN-2, and MPANC-96 XENOGRAFTS.

    Journal of Labelled Compounds and Radiopharmaceuticals. Vol 48, Issue S1, Page S58. Abstract. (http://onlinelibrary.wiley.com/doi/10.1002/jlcr.978/epdf) 2005

  • Antiseptic derivatives with broad spectrum antimicrobial activity for the impregnation of surfaces.

    United States Patent 7,713,472. (http://www.google.com/patents/US7713472) 2010

  • Medical devices with broad spectrum antimicrobial activity.

    United States Patent 7,651,661, Jan 26, 2010. (https://www.google.com.au/patents/US7651661) 2010

See list of PubMed publications

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Contact Info

Nabeel Nabulsi, PhD
Synapses of a living human brain.

Imaging synaptic density in the living human brain. Visualization of healthy or aberrant neuronal connections in the living brain—tissues is now possible using positron emission tomography (PET). The synaptic vesicle glycoprotein 2A (SV2A) radioligand [11C]UCB-J and PET offers a non-invasive method for quantifying synaptic density in the living human brain.