Dr. Ali Azhdarinia, Ph.D.

Dr. Ali Azhdarinia, Ph.D.

Associate Professor, Center for Precision Biomedicine

Email Address: Ali.Azhdarinia@uth.tmc.edu
Phone Number: 713-500-3577
Room Number: 3SCR6.4680

Narrative

Development of Theranostic Agents

Ali Azhdarinia, Ph.D. is an Associate Professor of Molecular Medicine in the Brown Foundation Institute of Molecular Medicine at the University of Texas Health Science Center at Houston. Dr. Azhdarinia received his Bachelor’s degree in Biology from the University of Houston, followed by completion of his Master’s degree and Ph.D. in Pharmacology from the University of Texas Graduate School of Biomedical Sciences in Houston. His research training was in the area of contrast agent development with a focus on radiopharmaceutical development. At UTHealth, Dr. Azhdarinia runs the Theranostics Laboratory in the Center for Precision Biomedicine (PBM).  His research interests include the development of targeted agents for the visualization and treatment of cancer.  Dr. Azhdarinia has served as the leader of the National Cancer Network’s Network for Translational Research (NTR) Chemistry Core and is heavily involved in validation and qualification of preclinical theranostic compounds. His work utilizes radioactive and near-infrared fluorescent (NIRF) contrast agents which can be used for whole-body and intraoperative imaging, respectively, and may potentially improve surgical outcomes while minimizing morbidities associated with current methods.  The combination of both modalities into a single agent is a key area where Dr. Azhdarinia has focused his efforts through synthesis of a library of new multimodal chelation (MMC) platforms.  His lab also conducts full pharmacological characterization of lead compounds to determine suitability for clinical translation.  Importantly, expertise in chemistry, imaging, and drug characterization has allowed Dr. Azhdarinia to establish diverse collaborations that are focused on translation of discoveries and technologies into the clinic to improve human health. 

RESEARCH PROJECTS

  • Development of contrast agents for fluorescence-guided surgery
  • Novel strategies for targeted drug delivery
  • Synthesis of chelation platforms for drug development and characterization

SELECTED PUBLICATIONS

  1. Hernandez Vargas,, Kossatz, S., Voss, J., Ghosh, S.C., Tran Cao, H.S., Simien, J., Reiner, T., Dhingra, S., Fisher, W.E., Azhdarinia, A.* Specific targeting of somatostatin receptor subtype-2 for fluorescence-guided surgery. Clin Cancer Res. 25(14):4332-4342, 2019. PMID: 31015345.
  2. Hernandez Vargas,, Ghosh, S.C., Azhdarinia, A.* New Developments in Dual-labeled Molecular Imaging Agents. J Nucl Med. 60(4):459-465, 2019. PMID: 30733318.
  3. Carmon, K.S. and Azhdarinia, A.* Application of ImmunoPET in Antibody-Drug Conjugate Development. Mol Imaging Jan-Dec;17:1536012118801223, 2018. PMID:30370812.
  4. Azhdarinia, A., Voss, J., Ghosh, S.C., Simien, J.A., Hernandez Vargas, S., Cui, J., Yu, W.A., Liu, Q., and Carmon, K.S. Evaluation of anti-LGR5 Antibodies by ImmunoPET for Imaging Colorectal Tumors and Development of Antibody-Drug Conjugates. Mol Pharm. 4;15(6):2448-2454, 2018. PMID:29718672.
  5. Ghosh, S.C., Hernandez Vargas, S., Rodriguez, M., Kossatz, S., Voss, J., Carmon, K.S., Reiner, T., Schonbrunn, A., Azhdarinia, A.* Synthesis of a Fluorescently Labeled 68Ga-DOTA-TOC Analog for Somatostatin Receptor Targeting. ACS Med Chem Lett. 6;8(7):720-725, 2017. PMID:28740605.
  6. Ghosh, S.C., Rodriguez, M., Carmon, K.S., Voss, J., Wilganowski, N.L., Schonbrunn, A., Azhdarinia, A.* A Modular Dual Labeling Scaffold That Retains Agonistic Properties for Somatostatin Receptor Targeting. Nucl Med. 58(11):1858-1864, 2017. PMID:28572490.
  7. Pinkston, K.L., Gao, P., Singh, K.V., Azhdarinia, A., Murray, B.E., Sevick-Muraca, E.M., Harvey, B. Antibody Guided Molecular Imaging of Infective Endocarditis. Methods Mol Biol.1535:229-241, 2017. PMID:27914083.
  8. Gong, X., Azhdarinia, A., Ghosh, S.C., Xiong, W., An, Z., Liu, Q., Carmon, K.S. LGR5-targeted antibody-drug conjugate eradicates gastrointestinal tumors and prevents recurrence. Mol Cancer Ther. 15(7):1580-90, PMID:27207778.
  9. Massaad, C., Zhang,, Pillai, L., Azhdarinia, A., Liu, W., Sheikh, K. Fluorescently-tagged anti-ganglioside antibody selectively identifies peripheral nerve in living animals. Sci Rep. 30;5:15766, 2015. PMID:26514366.
  10. Ghosh, S.C. and Azhdarinia, A.* Advances in the Development of Multimodal Imaging Agents for Nuclear/ Near-infrared Fluorescence Imaging. Curr Med Chem. 22(29):3390-404, 2 PMID:26337105.
  11. Ghosh, S.C., Pinkston, K.L., Robinson, H., Harvey, B.R., Wilganowski, N., Gore, K., Sevick-Muraca, E.M., Azhdarinia, A.* Comparison of DOTA and NODAGA as Chelators for 64Cu-labeled Immunoconjugates. Nucl Med Biol. 42(2):177-83, 2015. PMID:25457653.
  12. Gao, P., Pinkston, K.L., Wilganowski, N., Robinson, H., Azhdarinia, A., Zhu, B., Sevick-Muraca, E.M., Harvey, B.R. Deglycosylation of mAb by EndoS for Improved Molecular Imaging. Mol Imaging Biol. 17(2):195-203, 2014. PMID:25135058.
  13. Pinkston, K., Singh, K., Gao, P., Wilganowski, N., Robinson, H., Ghosh, S., Azhdarinia, A., Sevick-Muraca, E., Murray, B., Harvey, B. Targeting Pili in Enterococcal Pathogenesis. Infect. Immun. 82(4):1540-7, 2014. PMID:24452680.
  14. Nordstrom, R., Cherry, S., Azhdarinia, A., Sevick-Muraca, E., Vanbrocklin, H. Photons across medicine: relating optical and nuclear imaging. Biomed Opt Express. 4(12):2751-62, 2013. PMID:24409377.
  15. Azhdarinia, A., Daquinag, A.C., Tseng, C., Ghosh, S.C., Ghosh, P., Amaya-Manzanares , Sevick-Muraca, E.M., Kolonin, M.G. Probes for targeted brown adipose tissue imaging. Nat Commun. 4:2472, 2013. PMID: 24045463.
  16. Sevick-Muraca, E.M., Akers, W.J., Joshi, B.P., Luker, G.D., Marnett, L.J., Contag, C.H., Wang, T.D., Azhdarinia, A.* Advancing the translation of optical imaging agents for clinical medical imaging. Biomedical Opt Express. 4(1): 160-70, 2013. PMID:23304655.
  17. Ghosh, S.C., Ghosh, P., Wilganowski, N., Robinson, H., Hall, M.A., Dickinson, G., Harvey, B., Sevick-Muraca, E.M., Azhdarinia, A.* A Multimodal Chelation Platform for Near-infrared Fluorescence/Nuclear Imaging. J Med Chem. 56(2):406-16, 2013. PMID:23214723.
  18. Hall, M.A., Pinkston, K.L., Wilganowski, N., Robinson, H., Ghosh, P., Azhdarinia, A., Vasquez-Arreguin, K., Kolonin, A.M., Chan, W., Harvey, B.R., Sevick-Muraca, E.M. Comparison of mAbs targeting EpCAM for detection of prostate cancer lymph node metastases with multimodal contrast: NIRF imaging and quantitative µPET/CT. J Nucl Med.53(9):1427-37, 2012. PMID:22872743.
  19. Moss, J.A., Vavere, A.L., Azhdarinia, A.* Design of Peptide Imaging Agents for Whole-body and Intraoperative Molecular Imaging. Curr Med Chem. 1;19(20):3255-65, 2012. PMID:22664243.
  20. Azhdarinia, A.*, Ghosh, P., Ghosh, S., Wilganowski, N., Sevick-Muraca, E.M. Dual-labeling Strategies for Nuclear and Fluorescence Molecular Imaging: a Review and Analysis. Mol Imaging Biol. 14(3):261-76, 2012. PMID:22160875.


Fig1

Figure 1. Structure and components of the SSTR2-targeted intraoperative imaging agent. MMC-mediated dual labeling enables quantitative characterization of the fluorescent somatostatin analog, MMC(IR800)-TOC. (From Hernandez Vargas et al., Clin Cancer Res, 2019).


Fig2

Figure 2. In vivo and ex vivo specificity of Ga-MMC(IR800)-TOC. (A) In vivo NIRF imaging in HCT116-SSTR2 and HCT116-WT subcutaneous xenografts acquired 24 h post-injection with a custom-built EMCCD fluorescence imaging system, arrows indicate tumor. (B) Ex vivo NIRF imaging of selected organs using an IVIS Lumina II. (C) Tissue fluorescence determined from analysis of IVIS imaging. (D) Optical contrast provided by the ratio of the average fluorescent signal in the tumor to sites of NET formation. * P< 0.05, ** P< 0.01, ***P< 0.001. Data are presented as mean ± standard deviation (n=5). Average radiant efficiency displayed as ([p/s/cm²/sr]/[µW/cm²]). (From Hernandez Vargas et al., Clin Cancer Res, 2019).


Fig3

Figure 3. Proof-of-principle of Ga-MMC(IR800)-TOC binding to human NETs. Mesoscopic Odyssey scans show Ga-MMC(IR800)-TOC uptake is confined to tumor areas in human NET biospecimens, while uptake in normal tissue was very low. (Adapted from Hernandez Vargas et al., Clin Cancer Res, 2019).