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Departments & Divisions
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PET Section Chief, Neurodegeneration Radiochemistry, Research Imaging Institute
Director of Research Radiochemistry, Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases
Assistant Professor, Department of Radiology
Research & Clinical Interests
Research in the Molecular Imaging Probes and Radiochemistry Laboratory is directed towards the discovery of radiopharmaceuticals for both studying biochemical and pharmaceutical mechanisms in living systems, and diagnosis of disease conditions. Specific ligands for imaging targets (a-Syn, b-Amyloid and tau) include ones relevant for Alzheimer’s, Parkinson’s and other related disorders. In support of these goals the lab also develops innovative chemical methodologies for small molecule bioconjugation with short-lived radioactive isotopes such as carbon-11 and fluorine-18.
Awards and Honors:
Research in the Molecular Imaging Probes and Radiochemistry Laboratory is directed towards the discovery of radiopharmaceuticals for both studying biochemical and pharmaceutical mechanisms in living systems, and diagnosis of disease conditions. Specific ligands for imaging targets (a-Syn, b-Amyloid and tau) include ones relevant for Alzheimer’s, Parkinson’s and other related disorders. In support of these goals the lab also develops innovative chemical methodologies for small molecule bioconjugation with short-lived radioactive isotopes such as carbon-11 and fluorine-18.
Invention filed in 2019: “PET Tracers for alpha-synuclein (a-syn) Imaging” and Technology ID: HSC-1616.
Current Grants: 06/2019- 08/2020
Non-Federal:
“Tau Imaging: A Tool for Alzheimer’s Disease Research and Clinical Management”
Overall goal of Tau imaging project is developing PET radiotracers for Alzheimer’s disease diagnosis. The newly generated tau PET radioligands will be validated using post-mortem human tissue and in vivo using mouse models of tauopathy.
Role: Principal-Investigator
“Alpha-synuclein imaging: A tool for Parkinson’s disease research and clinical management”
Overall goal of alpha-Synuclein imaging project is developing PET radiotracers for Parkinson’s disease diagnosis. The newly generated Alpha-synuclein PET radioligands will be validated using post-mortem human tissues.
Role: Principal-Investigator
Federal:
Funding Agency: NIH/NIBIB R03 (Neelamegam - PI) 08/01/2020 – 05/31/2022;
Direct Cost $100,000
Title of Project: “Development of an optimized thermal deprotection method for the synthesis 18F-based radiopharmaceuticals.”
Overall goal of R03 project is developing 18F-based radiopharmaceuticals for Alzheimer’s & neurodegenerative diseases.
Role: Principal-Investigator
Funding Agency: National Science Foundation.
Title of Project: “SBIR Phase I: Sensitive and Rapid Endotoxin Assays via a Unique Optical Biosensor-Based Limulus Amoebocyte Lysate Test.”
Overall goal of the project will address endotoxin testing for pharmaceutical quality control. The proposed approach will use a different physical parameter, refractive index (RI), to sensitively monitor the early onset of the gel-forming process in a mixture of analyte solution and Limulus Amoebocyte Lysate (LAL).
Role: Serving as a consultant and performing proposed endotoxin testing experiments at the cyclotron facility. Radiopharmaceutical testing will be performed at the Research Imaging Institute, UT Health San Antonio, Texas.
PET radiotracers are available for imaging studies to UTHSA and collaborating Principal Investigators within the San Antonio area.
Selected Publications:
Yokell, D. L., Rice, P. A., Neelamegam, R., & El Fakhri, G. (2020). Development, validation and regulatory acceptance of improved purification and simplified quality control of [13N] Ammonia. EJNMMI radiopharmacy and chemistry, 5(1), 11. https://doi.org/10.1186/s41181-020-00097-7
L 'Estrade ET, Shalgunov V, Edgar FG, Strebl-Bantillo MG, Xiong M, Crestey F, Neelamegam, R., Dyssegaard, A., Lehel, S., Erlandsson, M., Ohlsson, T., Hooker, J. M., Knudsen, G. M., Herth, M, M., Hansen, H, D,. (2020). Radiosynthesis and preclinical evaluation of [11C]Cimbi-701 - Towards the imaging of cerebral 5-HT7 receptors. J Labelled Comp Radiopharm. 2020 Feb;63(2):46-55. doi: 10.1002/jlcr.3808. Epub 2020 Jan 6. PMID: 31674045.
Aguero, C., Dhaynaut, M., Normandin, M. D., Amaral, A. C., Guehl, N. J., Neelamegam, R., Marquie, M., Johnson, K. A., El Fakhri, G., Frosch, M. P., & Gomez-Isla, T. (2019). Autoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue. Acta neuropathologica communications, 7(1), 37. https://doi.org/10.1186/s40478-019-0686-6
Lan, Y., Bai, P., Chen, Z., Neelamegam, R., Placzek, M. S., Wang, H., Fiedler, S. A., Yang, J., Yuan, G., Qu, X., Schmidt, H. R., Song, J., Normandin, M. D., Ran, C., & Wang, C. (2019). Novel radioligands for imaging sigma-1 receptor in brain using positron emission tomography (PET). Acta pharmaceutica Sinica. B, 9(6), 1204–1215. https://doi.org/10.1016/j.apsb.2019.07.002
Verwer, E. E., Kavanagh, T. R., Mischler, W. J., Feng, Y., Takahashi, K., Wang, S., Shoup, T. M., Neelamegam, R., Yang, J., Guehl, N. J., Ran, C., Massefski, W., Cui, Y., El-Chemaly, S., Sadow, P. M., Oldham, W. M., Kijewski, M. F., El Fakhri, G., Normandin, M. D., & Priolo, C. (2018). [18F]Fluorocholine and [18F]Fluoroacetate PET as Imaging Biomarkers to Assess Phosphatidylcholine and Mitochondrial Metabolism in Preclinical Models of TSC and LAM. Clinical cancer research : an official journal of the American Association for Cancer Research, 24(23), 5925–5938. https://doi.org/10.1158/1078-0432.CCR-17-3693
Placzek, M. S., Schroeder, F. A., Che, T., Wey, H. Y., Neelamegam, R., Wang, C., Roth, B. L., & Hooker, J. M. (2019). Discrepancies in Kappa Opioid Agonist Binding Revealed through PET Imaging. ACS chemical neuroscience, 10(1), 384–395. https://doi.org/10.1021/acschemneuro.8b00293
Collier, T. L., Yokell, D. L., Livni, E., Rice, P. A., Celen, S., Serdons, K., Neelamegam, R., Bormans, G., Harris, D., Walji, A., Hostetler, E. D., Bennacef, I., & Vasdev, N. (2017). cGMP production of the radiopharmaceutical [18F]MK-6240 for PET imaging of human neurofibrillary tangles. Journal of labelled compounds & radiopharmaceuticals, 60(5), 263–269. https://doi.org/10.1002/jlcr.3496
Neelamegam, R., Yokell, D. L., Rice, P. A., Furumoto, S., Kudo, Y., Okamura, N., & El Fakhri, G. (2017). A report of the automated radiosynthesis of the tau positron emission tomography radiopharmaceutical, [18F]-THK-5351. Journal of labelled compounds & radiopharmaceuticals, 60(2), 140–146. https://doi.org/10.1002/jlcr.3482
Strebl, M. G., Wang, C., Schroeder, F. A., Placzek, M. S., Wey, H. Y., Van de Bittner, G. C., Neelamegam, R., & Hooker, J. M. (2016). Development of a Fluorinated Class-I HDAC Radiotracer Reveals Key Chemical Determinants of Brain Penetrance. ACS chemical neuroscience, 7(5), 528–533. https://doi.org/10.1021/acschemneuro.5b00297
Schroeder, F. A., Wang, C., Van de Bittner, G. C., Neelamegam, R., Takakura, W. R., Karunakaran, A., Wey, H. Y., Reis, S. A., Gale, J., Zhang, Y. L., Holson, E. B., Haggarty, S. J., & Hooker, J. M. (2014). PET imaging demonstrates histone deacetylase target engagement and clarifies brain penetrance of known and novel small molecule inhibitors in rat. ACS chemical neuroscience, 5(10), 1055–1062. https://doi.org/10.1021/cn500162j
Ren, H., Wey, H. Y., Strebl, M., Neelamegam, R., Ritter, T., & Hooker, J. M. (2014). Synthesis and imaging validation of [¹⁸F]MDL100907 enabled by Ni-mediated fluorination. ACS chemical neuroscience, 5(7), 611–615. https://doi.org/10.1021/cn500078e
Huang, X., Liu, W., Ren, H., Neelamegam, R., Hooker, J. M., & Groves, J. T. (2014). Late stage benzylic C-H fluorination with [¹⁸F]fluoride for PET imaging. Journal of the American Chemical Society, 136(19), 6842–6845. https://doi.org/10.1021/ja5039819
Neelamegam, R., Hellenbrand, T., Schroeder, F. A., Wang, C., & Hooker, J. M. (2014). Imaging evaluation of 5HT2C agonists, [(11)C]WAY-163909 and [(11)C]vabicaserin, formed by Pictet-Spengler cyclization. Journal of medicinal chemistry, 57(4), 1488–1494. https://doi.org/10.1021/jm401802f
Wang, C., Eessalu, T. E., Barth, V. N., Mitch, C. H., Wagner, F. F., Hong, Y.,
Neelamegam, R., Schroeder, F. A., Holson, E. B., Haggarty, S. J., & Hooker, J. M. (2013). Design, synthesis, and evaluation of hydroxamic acid-based molecular probes for in vivo imaging of histone deacetylase (HDAC) in brain. American journal of nuclear medicine and molecular imaging, 4(1), 29–38.
Granda, M. L., Carlin, S. M., Moseley, C. K., Neelamegam, R., Mandeville, J. B., & Hooker, J. M. (2013). Synthesis and evaluation of methylated arylazepine compounds for PET imaging of 5-HT(2c) receptors. ACS chemical neuroscience, 4(2), 261–265. https://doi.org/10.1021/cn300223d
Moseley, C. K., Carlin, S. M., Neelamegam, R., & Hooker, J. M. (2012). An efficient and practical radiosynthesis of [11C]temozolomide. Organic letters, 14(23), 5872–5875. https://doi.org/10.1021/ol302791x
Neelamegam, R., Ricq, E. L., Malvaez, M., Patnaik, D., Norton, S., Carlin, S. M., Hill, I. T., Wood, M. A., Haggarty, S. J., & Hooker, J. M. (2012). Brain-penetrant LSD1 inhibitors can block memory consolidation. ACS chemical neuroscience, 3(2), 120–128. https://doi.org/10.1021/cn200104y