John R. Lever, Ph.D.
Research Interests
Our research centers upon the development of novel radioactive tracers, and their use in vitro and in vivo to gain a better understanding of neoplastic disease, substance abuse and neurological function. Areas of current interest include: 1) radioligands for studies of receptor systems (e.g., opioid and sigma) that facilitate non-invasive detection and biochemical characterization of certain cancers; and 2) photoaffinity probes for the dopamine transporter / cocaine receptor. The research is inherently multidisciplinary, and falls under the general heading of molecular pharmacology. Our group performs organic and organometallic synthesis, radiolabeling with isotopes of iodine and indium, in vitro binding assays, and in vivo biodistribution studies of novel radiotracers in normal mice and in rodent xenograft models of human cancers. As appropriate, in vivo work can be extended to include functional radionuclide imaging (microSPECT, microPET) aided by anatomical (microCT, microMRI) or optical imaging.
Professional Background
- B.S. in Chemistry, University of South Carolina
- Ph.D. in Organic Chemistry, North Carolina State University
- Postdoctoral Fellowship, The Johns Hopkins University
- Primary appointment, MU Radiology; Joint appointment, MPP (2003)
- Reviewer: J Med Chem, Bioconjugate Chem, Nucl Med Biol
- Ad hoc member: NIH study sections, VA review panels
- Scientific program reviews: Society of Nuclear Medicine
- Funding: National Cancer Institute, National Institute on Drug Abuse
Selected Publications
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Lever JR, Gustafson JL, Xu R, Allmon RL, Lever SZ: Sigma1 and sigma2 receptor binding affinity and selectivity of SA4503 and fluoroethyl SA4503. Synapse, in press, 2006.
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Lever JR, Zou M-F, Parnas ML, Duval RA, Wirtz SE, Justice JB, Vaughan RA, Newman AH: Radioiodinated azide and isothiocyanate derivatives of cocaine for irreversible labeling of dopamine transporters: synthesis and covalent binding studies. Bioconjugate Chem 16:644-649, 2005.
- Duval RA, Allmon RL, Gustafson JL, Carmack TL, Watkinson LD, Lever JR: An indium-labeled DO3A conjugate of naltrindole with high affinity and selectivity for delta opioid receptors: synthesis, binding studies and biodistribution. J Label Compd Radiopharm 48:S8, 2005.
- Cao J, Lever JR, Kopajtic T, Katz JL, Pham AT, Holmes ML, Justice JB, Newman AH: Novel azido and isothiocyanato analogues of [3-(4-phenylalkyl piperazin-1-yl)propyl]bis(4-fluorophenyl)amines as potential irreversible ligands for the dopamine transporter. J Med Chem 47:6128-6136, 2004.
Methodologies/Techniques
Radiotracer design and synthesis, in vitro and in vivo radioligand binding studies, autoradiography, nuclear imaging, rodent tumor models.
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