Dr. Ali Azhdarinia, Ph.D.

Dr. Ali Azhdarinia, Ph.D.

Associate Professor, Center for Translational Cancer Research

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

Narrative

DEVELOPMENT OF THERANOSTIC AGENTS

My laboratory is at the interface of chemistry and biology and is focused on developing molecules for the visualization and treatment of disease. Using novel chemistry platforms, we have the ability to produce molecules with multiple labels and thus, multiple applications.  For example, the addition of radioactive and fluorescent labels onto tumor-seeking agents has allowed us to develop new approaches to specifically identify cancer by whole-body and intraoperative imaging, respectively.   This could potentially provide surgeons with real-time intraoperative images that will distinguish cancer from normal tissue, minimize removal of healthy tissues, and identify small tumors which would otherwise be missed by the naked eye.  In cases where cancer has spread and surgery is not possible, we use our chemistry platform to selectively deliver toxins to tumors and visualize their effects in vivo, enabling personalized treatment protocols.  Our fundamental expertise in chemistry, imaging, and drug characterization has allowed us to establish diverse collaborations to study the in vivo properties of novel disease-targeted molecules, evaluate the potential benefits of modulating biomarker trafficking in cancer cells, and assess the effectiveness of emerging cancer treatments. Common to each project is our focus on translation of discoveries and technologies into the clinic to improve human health. 

PROJECTS

  • Development of contrast agents for fluorescence-guided surgery and nuclear imaging
  • Targeted drug delivery
  • Synthesis of chelation platforms for drug development and characterization

SELECTED PUBLICATIONS

  1. Usama, S.M., Marker, S.C., Hernandez Vargas, S., AghaAmiri, S., Ghosh, S.C., Ikoma, N., Tran Cao, H.S., Schnermann, M.J., Azhdarinia, A.* Targeted Dual-Modal PET/SPECT-NIR Imaging: From Building Blocks and Construction Strategies to Applications. Cancers. 14(7), 1619, 2022. https://doi.org/10.3390/cancers14071619.
  2. Subramanian, S., Daquinag, A., AghaAmiri, S., Ghosh, S.C., Azhdarinia, A., Kolonin, M.G. Characterization of peptides targeting metastatic tumor cells as probes for cancer detection and vehicles for therapy delivery. Cancer Res. 15;81(22):5756-5764, 2021. doi: 10.1158/0008-5472.CAN-21-1015. PMID: 34607842.
  3. Hernandez Vargas, S., Lin, C., Tran Cao, H., Ikoma, N., AghaAmiri, S., Ghosh, S., Uselmann, A., and Azhdarinia, A.* Receptor-targeted fluorescence-guided surgery with low molecular weight agents. Frontiers in Oncology. 11:674083. Front Oncol. 11:674083. doi: 10.3389/fonc.2021.674083. eCollection 2021. PMID: 34277418.
  4. Orouji, E., Raman, A.T., Singh, A.K., Sorokin, S., Ghosh, A.K., Terranova, C.J., Tang, M., Maitituoheti, M., Callahan, S.C., Tomczak, K., Jiang, Z., Davis, J.S. Ghosh, S., Lee, H.M., Reyes-Uribe, L., Chang, K., Liu, Y., Chen, H., Azhdarinia, A., Morris, J.S., Vilar, E., Carmon, K.S., Kopetz, S., Rai, K. Chromatin state dynamics confers specific therapeutic strategies in enhancer subtypes of colorectal cancer. Gut. doi:10.1136/gutjnl-2020-322835, 2021. PMID: 34059508.
  5. AghaAmiri, S., Simien, J., Thompson, A.M., Voss, J., Ghosh,C., Hernandez Vargas, S., Kim, S., Azhdarinia, A.*, Tran Cao, H.S. Comparison of HER2-targeted antibodies for fluorescence-guided surgery in breast cancer. Mol Imaging. p. 5540569, 2021. PMID: 34194285.
  6. Hernandez Vargas, S., Lin, C., Voss, J., Ghosh, S., Halperin, D.M., AghaAmiri, S., Tran Cao, H., Ikoma, N., Uselmann, A., and Azhdarinia, A.* Development of a drug-device combination for fluorescence-guided surgery in neuroendocrine tumors. J Biomed Opt. 25(12):126002, 2020. PMID: 33300316.
  7. Hernandez Vargas, S., Lin, C., AghaAmiri, S., Voss, J., Ikoma, N., Tran Cao, H., Ghosh, S., Uselmann, A., and Azhdarinia, A.* A proof-of-concept methodology to validate the in situ visualization of residual disease using cancer-targeted molecular agents in fluorescence-guided surgery. SPIE BiOS. Vol. 11222, 2020. PMID: 34054189.
  1. Hernandez Vargas, S., 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, S., 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. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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).