JOHN M. HOFFMAN

John Hoffman

e-mail: john.hoffman@hci.utah.edu
Willard Snow Hansen Presidential Endowed Chair in Cancer Research
Professor of Radiology and Neurology

Director of Nuclear Medicine
Director: Molecular Imaging Program, Huntsman Cancer Institute

The Hoffman lab
Brain and Behavior
B.S.E. 1977, University of Pennsylvania; M.D. 1980, University of Colorado; Residency, Neurosurgery 1981-1983, University of Washington, Seattle, WA; Residency, Neurology 1983-1986, University of Washington, Seattle, WA; Fellowship, Nuclear Medicine/PET 1986-1989, UCLA School of Medicine, Los Angeles, CA

RESEARCH:

Modern imaging techniques including positron emission tomography (PET), MRI, and autoradiography to understand clinically relevant brain related problems and biologic processes

Dr. Hoffman has a particular interest in the use of PET imaging as a biomarker in therapeutic drug trials and in personalized medicine. He has many years experience, background, and knowledge of the regulatory approval process for PET imaging agents. He has filed eight Investigational New Drug (IND) applications during his academic career. His own research activities include the use of PET imaging techniques to assess malignancy in both basic science studies and clinical trials; assessment of early response to cancer therapy; and in studying disorders of the nervous system. Other focuses of his research are in the use of PET imaging to understand cancer-associated physiologic changes and complications including the effects of chemotherapy on cognitive function, cardiac function, and muscle weakness/fatigue. Specific projects include:

  • Studies to assess the efficacy of various PET radiopharmaceuticals used alone and in combination to assess the biology of brain tumors before and after treatment
  • Studies using quantitative FDG-PET, functional MRI (fMRI) with several activation paradigms, an extensive neuropsychological test battery, and co-registered anatomic MRI imaging to better understand the cognitive disorder known as "chemobrain".
  • Studies comparing various image interpretation strategies and parameters in patients with dementia
  • Studies using FDG and the novel imaging agent [C-11]PIB to explore the biodistribution of amyloid plaques in various dementia syndromes.
  • Studies using advanced imaging techniques are being explored to better understand the pathophysiology of heavy metal deposition and metabolism in brain trauma, sepsis, and degenerative neurologic conditions such as Alzheimer's disease.

    Selected Publications:

    Foster, N.L., Wang, A.Y., Tasdizen, T., Fletcher, P.T., Hoffman, J.M., and Koeppe, R.A. (2008) Realizing the potential of positron emission tomography with 18F-fluorodeoxyglucose to improve the treatment of Alzheimer's disease. Alzheimer Dement, 4(S1):S29-36.

    Hammoud, D., Hoffman, J.M., and Pomper, M.G. (2007) Molecular neuroimaging: from conventional to emerging techniques. Radiology, 245(1):21-42.

    Neuwelt, E.A., Várallyay, C., Manninger, S., Solymosi, D., Hunt, M.A., Jerosch-Herold, M., Stevens, A., Nesbit, G., Kraemer, D., and Hoffman, J.M. (2007) Assessment of MR imaging, perfusion, and angiography using ferumoxytol nanoparticles in CNS malignancy. Neurosurgery, 60:601-612.

    Schweitzer, J.B., Lee, D.O., Hanford, R.B., Zink, C.F., Ely, T.D., Tagamets, M.A., Hoffman, J.M., Grafton, S.T., and Kilts, C.D. (2004) A Neuroimaging Study of the Effect of Methylphenidate on Working Memory in Adults with ADHD: Normalization of Behavior but not Brain Activity. Biological Psychiatry, 56:597-606.

    Davis, M.R., Votaw, J.R., Bremner, J.D., Byas-Smith, M.G., Faber, T.L., Vol, R.J.l., Watts, R.L., Hoffman, J.M., Kilts, C.D., and Goodman, M.M. (2003) Initial PET Imaging Studies with the Dopamine Transporter Ligand [18F]-FECNT. J Nucl Med, 44(6):855-861.

    Turner, R.S., Grafton, S.T., McIntosh, A.R., DeLong, M.R., and Hoffman, J.M. (2003) The Functional Anatomy of Parkinsonian Bradykinesia. NeuroImage, 19(1):163-179.

    Tune, L., Tiseo, P., Ieni, J., Perdomo, C., Pratt, R.D., Votaw, J.R., Jewart, R.D., and Hoffman, J.M. (2003) Donezepil HCL (E2020) Maintains Functional Brain Activity in Patients with Alzheimer's Disease: Results of a 24-Week, Double-Blind, Placebo-Controlled Study. Am J Geriatr Psychiatry, 11:169-177.

    Schweitzer, J.B., Lee, D., Hanford, Tagamets, M.A., Hoffman, J.M., Grafton, S.T., and Kilts, C.D. (2003) A Positron Emission Tomography Study of Methylphenidate in Adults with ADHD: Alterations in Resting Blood Flow and Predicting Treatment Response. Neuropsychopharmacology, 20(5):967-973.

    Kilts, C.D., Egan, G., Gideon, D.A., Ely, T.D., and Hoffman, J.M. (2003) Dissociable neural pathways are involved in the recognition of emotion in static and dynamic facial expressions. Neuroimage, Jan;18(1):156-168.

    Byas-Smith, M., Frolich, M., Votaw, J., Faber, T., and Hoffman, J.M. (2002) Cerebral Blood Flow During Propofol Induced Sedation. Molecular Imaging and Biology, 4(2):139-146.

    Votaw, J.R., Howell, L.L., Martarello, L., Hoffman, J.M., Kilts, C.D., and Goodman, M.M. (2002) Measurement of Dopamine Transporter Occupancy for Multiple Injections of Cocaine Using a Single Injection of [F-18]FECNT. Synapse, 44:203-210.

    Silverman, D.H.S., Small, G.W., Chang, C.Y., Lu, C.S., Kung de Aburto, M.A., Chen, W., Czernin, J., Rapoport, S.I., Pietrini, P., Gene, E., Alexander, G.E., Schapiro, M.B., Jagust, W.J., Hoffman, J.M., Welsh-Bohmer, K.A., Alavi, A., Clark, C.M., Eric Salmon, E., de Leon, M.J., Mielke, R., Cummings, J.L., Kowell, A.P., Gambhir, S.S., Hoh, C.K., Michael, E., and Phelps, M.E. (2001) Neuroimaging in Evaluation of Dementia: Regional Brain Metabolism and Long-Term Outcome. JAMA, 286(7):2120-2127.

    Kilts, C., Schweitzer, J., Quinn, C., Gross, R., Faber, T., Muhammad, F., Hoffman, J.M., and Drexler, K. (2001) Functional Anatomy of Drug Craving in Human Cocaine Addiction. Arch Gen Psychiatry, 58:334-341.

    Rilling, J.K., Winslow, J.T., O'Brien, D.O., Gutman, D.A., Hoffman, J.M., and Kilts, C.D. (2001) Neural Correlates of Maternal Separation in Rhesus Monkey. Biological Psychiatry, 49(2):146-157.

    Deterding, T.A., Votaw, J.R., Wang, C.K., Eshima, D., Eshima, L., Kiel, R., Malveux, E., Camp, V.M., Votaw, D.B., Kilts, C.D., Goodman, M.M., and Hoffman, J.M. (2001) Biodistribution and Radiation Dosimetry of the Dopamine Transporter Ligand: 2B-carbomethoxy-3B(4-chlorophenyl)-8-(2fluoroethyl)nortropane([18F]FECNT. J Nucl Med, 42:376-381.

    Hoffman, J.M., Welsh-Bohmer, K.A., Hanson, M.W., Crain, B.J., Hulette, C., Earl, N., and Coleman, R.E. (2000) FDG-PET Imaging in Pathologically Verified Dementia. J. Nucl. Med., 41(11):1920-1928.

    Goodman, M.M., Kilts, C., Keil, R., Shi, B., Martarello, L., Xing, D., Votaw, J., Ely, T., Lambert, P., Owens, M.J., Camp, V.M., Malveaux, E., and Hoffman, J.M. (2000) 18F-Labelled FECNT: A Selective Radioligand for PET Imaging of Brain Dopamine Transporters. Nucl Med Biol, 27(1):1-12.

    Votaw, J.R., Faber, T.L., Popp, C.A., Henry, T.R., Trudeau, J.D., Woodard, J.L., Mao, H., Woods, R.M., Hoffman, J.M., and Song, A.W. (1999) A Confrontational Naming Task Produces Congruent Activations and Deactivations in PET and fMRI. Neuroimage, 10:347-356.

    Henry, T.R., Votaw, J.R., Pennell, P.B., Epstein, C.M., Bakay, R.A.E., Faber, T.L., and Hoffman, J.M. (1999) Acute Blood Flow Changes and Efficacy of Vagus Nerve Stimulation in Partial Epilepsy. Neurology, 52:1166-1173.

    Shoup, T.M., Olson, J., Hoffman, J.M., Votaw, J., Eshima, D., Eshima, L., Camp, V.M., Votaw, D., and Goodman, M.M. (1999) Synthesis and Evaluation of [18F]-1-Amino-3-Fluoro-Cyclobutane-1-Carboxylic Acid to Image Brain Tumors. J.Nucl Med 40:331-338.

    Turner, R.S., Grafton, S.T., Votaw, J.R., DeLong, M.R., and Hoffman, J.M. (1998) Motor Subcircuits Mediating the Control of Movement Velocity: A PET Study. J Neurophysiology, 80:2162-2176.

    Woodard, J.L., Grafton, S.T., Votaw, J.R., Green, R.C., Dobraski, M., and Hoffman, J.M. (1998) Compensatory Recruitment of Neural Resources During Overt Rehearsal of Word Lists in Alzheimer's Disease. Neuropsychology, Vol 12(4):491-504.

    Madden, D.J., Turkington, T.G., Provenzale, J.M., Hoffman, J.M., and Coleman, R.E. (1997) Selective and Divided Attention: Age Realted Changes in Regional Cerebral Blood Flow Measured by H215O PET. Human Brain Mapping, 5:389-409.

    Goodman, M.M., Keil, R., Shoup, T.M., Eshima, D.E., Shattuck, L., Kilts, C., Votaw, J., Camp, V.M., Votaw, D., Smith, E., Kung, M.P., Malveaux, E., Watts, R., Huerkamp, M., Garcia, E., and Hoffman, J.M. (1997) Fluorine-18 FPCT: A PET radiotracer for imaging dopamine transporters. J Nucl Med, 38:119-126.

    Clower, D.M., Hoffman, J.M., Votaw, J.A., Faber, T.L., Woods, R.P., and Alexander, G.E. (1996) Selective Activation of Posterior Parietal Cortex During the Recalibration of Reaching that Accompanies Prism Adaptation. Nature, 383:618-621.

    Madden, D.J., Turkington, T.G., Coleman, R.E., Provencale, J.M., DeGrado, T.R., and Hoffman, J.M. (1996) Adult Age Differences in Regional Cerebral Blood Flow During Visual Word Identification. NeuroImage, 3:127-142.

    Schnieder, J.S., McLaughlin, W.W., Roeltgn, D.P., Hawk, T.C., Mazziotta, J.C., and Hoffman, J.M. (1995) Differential recovery of volitional motor function, lateralized cognitive function and dopamine agonist-induced rotation, and dopaminergic paramters in monkeys made hemi-Parkinsonian by intracarotid MPTP infusion. Brain Research, 672:112-127.

    Radtke, R.A., Hanson, M.W., Hoffman, J.M., Crain, B.J., Walszak, T.S., Lewis, D.V., Beam, C., Coleman, R.E., and Friedman, A.H. (1993) Temporal Lobe Hypometabolism on Positron Emission Tomography: Predictor of Seizure Control After Temporal Lobectomy. Neurology, 43:1088-1092.

    Hoffman, J.M., Waskin, H.A., Schifter, T., Hanson, M.W., Grey, L., Rosenfeld, S., and Coleman, R.E. (1993) FDG-PET in differentiating lymphoma from non-malignant central nervous system lesions in patients with AIDS. J Nucl Med, 34:567-575.

    Grafton, S.T., Mazziotta, J.C., Pahl, J.J., St. George-Hyslop, P., Haines, J.L., Gusella, J., Hoffman, J.M., Baxter, L.R., and Phelps, M.E. (1992) Temporal changes of cerebral glucose metabolism in persons at risk for Huntington's disease. Arch Neurology, 49:1161-1167.

    Hoffman, J.M., Melega, W.P., Hawk, T.C., Grafton, S.C., Luxen, A., Mahoney, D.K., Barrio, J.R., Huang, S.C., Mazziotta, J.C., and Phelps, M.E. (1992) The effects of carbidopa administration on 6 [18F] Fluoro L Dopa (FDOPA) kinetics in positron emission tomography (PET). J Nucl Med, 33:1472-1477.

    Hoffman, J.M., Mazziotta, J.C., Sumida, R., Hawk, T., and Phelps, M.E. (1992) Cerebral Glucose Utilization in Motor Neuron Disease. Arch Neurology, 49:849-854.

    Hoffman, J.M., Hanson, M.W., Friedman, H.S., Hockenberger, B., Oakes, J, and Coleman, R.E. (1992) The Use of FDG PET in the evaluation and management of pediatric posterior fossa tumors. J Comput Assist Tomogr, 16(1):62-68.

    Rosenfeld, S.S., Hoffman, J.M., Coleman, R.E., Glantz, M.J., Hanson, M.W., and Schold, S.C. (1992) Studies of Primary Central Nervous System Lymphoma with [18F] Fluorodeoxyglucose (FDG) Positron Emission Tomography. J Nuc Med, 33:532-536.

    Huang, S.C., Yu, D.C., Barrio, J.R., Grafton, S., Melega, W.P., Hoffman, J.M., Satyamurthy, N., Mazziotta, J.C., and Phelps, M.E. (1991) Kinetics and modeling of 6 [F 18] Fluoro L dopa in human positron emission tomographic studies. J Cereb Blood Flow Metab, 11:898-913.

    Melega, W.P., Hoffman, J.M., Schneider, J.S., Phelps, M.E., and Barrio, J.R. (1991) 6 [18F] Fluoro L DOPA metabolism in MPTP treated monkeys: assessment of tracer methodologies for positron emission tomography. Brain Research, 543:271-276.

    Glantz, M.J., Hoffman, J.M., Coleman, R.E., Friedman, A.H., Hanson, M.W., Burger, P.C., Herndon, J.E., Meisler, W.J., and Schold, S.C. (1991) The Role of F 18 FDG PET Imaging in Predicting Early Recurrence of Primary Brain Tumors. Ann Neurol, 29:347-355.

    Barrio, J.R., Huang, S.C., Melega, W.P., Yu, D.C., Hoffman, J.M., Schneider, J.S., Satyamurthy, N., Mazziotta, J.C., and Phelps, M.E. (1990) 6 [18] Fluoro L Dopa probes dopamine turnover rates in central dopaminergic structures. J Neuro Science Research, 27:487-493.

    Grafton, S.T., Mazziotta, J.C., Pahl, J.J., St George Hyslop, P., Haines, J.L., Guesella, J., Hoffman, J.M., Baxter, L.R., and Phelps, M.E. (1990) A Comparison of Neurologic, Metabolic, Structural, and Genetic Evaluations in Persons at Risk for Huntington's Disease. Ann Neurol, 28:614-621.

    Melega, W.P., Hoffman, J.M., Luxen, A., Nissenson, C.H.K., Phelps, M.E., and Barrio, J.R. (1990) The Effects of Carbidopa on the Metabolism of 6 [18F] fluoro L dopa in Rats, Monkey, and Humans. Life Sciences, 47:149-157.

    Lammertsma, A.A., Frackowiak, R.S.J., Hoffman, J.M., Huang, S.C., Weinberg, I.N., Dahlbom, M., McDonald, N.S., Hoffman, E.J., Mazziotta, J.C., Heather, J.D., Forse, G.R., Phelps, M.E., and Jones, T. (1989) The C15O2 Build Up Technique to Measure Regional Cerebral Blood Flow and Volume of Distibution of Water. Journal of Cerebral Blood Flow and Metabolism, 9:461-470.

    Hoffman, J.M., Rasey, J.S., Spence, A.M., Shaw, D.W., and Krohn, K.A. (1987) Binding of the Hypoxia Tracer [3H] Misonidazole in Cerebral Ischemia. Stroke, 18:No.1:168-176.

    Mazziotta, J.C., Phelps, M.E., Pahl, J.J., Huang, S.C., Baxter, L.R., Riege, W.H., Hoffman, J.M., Kuhl, D.E., Lanto, A.B., Wapenski, J.A., and Markham, C.H. (1987) Cerebral Glucose Utilization Reductions in Clinically Asymptomatic Subjects at Risk for Huntington's disease. New England J of Medicine, 16:7, 357-362.