The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases

 Ali Azhdarinia, Ph.D.

Ali Azhdarinia, Ph.D.

Assistant Professor, Center for Molecular Imaging

Ali.Azhdarinia@uth.tmc.edu

713-500-3577

Molecular Imaging Probe Development

Dr. Ali Azhdarinia received his Ph.D. in Pharmacology from the University of Texas Graduate School of Biomedical Sciences in Houston, focusing on the field of radiochemistry.  His research training was performed at the University of Texas M.D. Anderson Cancer Center and involved the development and characterization of novel imaging probes.  At UTHSC, Dr. Azhdarinia is the faculty lead of the Radio- and Optical-Pharmaceutical development effort in the Center for Molecular Imaging (CMI).  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 studies prior to translation in both NTR-wide and CMI local studies. 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 outcome 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.  The Azhdarinia Lab uses radiometal-based positron emitters, such as Gallium-68 and Copper-64, for labeling of peptides, proteins, and antibody-based agents.  His lab also conducts full pharmacological characterization of lead compounds to determine suitability for clinical translation.  As part of the Center for Molecular Imaging, Dr. Azhdarinia has participated in establishing a dedicated clean room for production of probes under Current Good Manufacturing Practices (cGMP) to facilitate translational research.  The Azhdarinia Lab is actively collaborating with clinical partners to establish creative approaches for translating “dual-labeled” agents.

RESEARCH PROJECTS

  • Development of molecular imaging probes with radioactive and near-infrared labels
  • Synthesis of novel chelation platforms for radiolabeling and drug design
  • Optimization of NIRF labeling methods
  • Pharmacological evaluation of imaging probes targeting tumors and other molecular processes

 

SELECTED PUBLICATIONS

  • Yang, D.J., Azhdarinia, A., Wu, P., Yu, D-F., Tansey, W., Kohanim, S., Kim, E.E., and Podoloff, D.A.  In Vivo and In Vitro Measurement of Apoptosis in Breast Cancer Cells Using 99mTc-EC- Annexin V.  Cancer Biother Radiopharm. 16(1):73-84, 2001. 
  • Yang, D.J., Kim, C-G., Schechter, N.R., Azhdarinia, A., Yu, D-F., Oh, C-S., Bryant, J.L., Won, J.J., Kim, E. E., Podoloff, D.A. Multifunctional Glucose Transport System Targeted Imaging Using 99mTc-EC-deoxyglucose.  Radiology. 226:465-473, 2003.
  • Schechter, N.R., Wendt, R.E. 3rd, Yang, D.J., Azhdarinia, A., Erwin, W.D., Stachowiak, A.M., Broemeling, L.D., Kim, E.E., Cox, J.D., Podoloff, D.A., Ang, K.K.  Radiation dosimetry of 99mTc-labeled C225 in patients with squamous cell carcinoma of the head and neck.  J Nucl Med. 45(10):1683-7, 2004.
  • Azhdarinia, A., Yang, D.J., Yu, D-F., Mendez, R., Oh, C., Kohanim, S., Bryant, J.L., Kim, E.E. Regional radiochemotherapy using in situ hydrogel.  Pharm Res. 22(5):776-83, 2005.
  • Azhdarinia, A., Yang, D.J., Chao, C., Mourtada, F.  Infrared-based module for synthesis of 68Ga-labeled radiotracers.  Nuc Med Biol. 34(1):121-7, 2007.
  • Takahashi, N., Yang, D.J., Kohanim, S., Oh, C.S., Yu, D.F., Azhdarinia, A., Kurihara, H., Zhang, X., Chang, J.Y., Kim, E.E. Targeted functional imaging of estrogen receptors with (99m)Tc-GAP-EDL.  Eur J Nucl Med Mol Imaging. 34(3): 354-362, 2007.
  • Schechter, N.R., Yang, D.J., Azhdarinia, A., Chanda, M.  Technologies for translational imaging using generators in oncology.  Recent Pat Anticancer Drug Discov. 2(3):251-8, 2007.
  • Hall, M.A., Kwon, S., Robinson, H., Lachance, P.A., Azhdarinia, A., Ranganathan, R., Price, R.E., Chan, W., Sevick-Muraca, E.M., Imaging prostate cancer lymph node metastases with a multimodality contrast agent. Prostate. 72, (2), 129-146, 2012.
  • Rodenberg, E., Azhdarinia, A., Lazard, Z.W., Hall, M., Kwon, S.K., Wilganowski, N., Salisbury, E.A., Merched-Sauvage, M., Olmsted-Davis, E.A., Sevick-Muraca, E.M., Davis, A.R., Matrix metalloproteinase-9 is a diagnostic marker of heterotopic ossification in a murine model. Tissue Eng Part A. 17(19-20), 2487-2496, 2011.
  • Azhdarinia, A., Wilganowski, N., Robinson, H., Ghosh, P., Kwon, S., Lazard, Z.W., Davis, A.R., Olmsted-Davis, E., Sevick-Muraca, E.M. Characterization of chemical, radiochemical and optical properties of a dual-labeled MMP-9 targeting peptide. Bioorg Med Chem. 19(12):3769-76, 2011.  PMID:21612930.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.
  • Hall, M.A., Aldrich, M.B., Azhdarinia, A., Lachance, P., Robinson, H., Hazen, A., Haviland, D.L., Sevick-Muraca, E.M. Quantifying multimodal contrast agent biological activity using near-infrared flow cytometry. Contrast Media Mol Imaging. 7(3):338-45. 2012. doi: 10.1002/cmmi.502. PMID: 22539404.
  • 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.
  • 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., and 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.
  • Ghosh, S.C., Ghosh, P., Wilganowski, N., Robinson, H., Hall, M.A., Dickinson, G., Harvey, B., Sevick-Muraca, E.M., and Azhdarinia, A. A Multimodal Chelation Platform for Near-infrared Fluorescence/Nuclear Imaging.  J Med Chem. 56(2):406-16, 2013. PMID:23214723.
  • Sevick-Muraca, E.M., Akers, W.J., Joshi, B.P., Luker, G.D., Marnett, L.J., Contag, C.H., Wang, T.D. and Azhdarinia, A. Advancing the translation of optical imaging agents for clinical medical imaging.  Biomedical Opt Express. 4(1): 160-70, 2013. PMID:23304655
  • Zhu, B., Wu, G., Robinson, H., Wilganowski, N., Hall, M.A., Ghosh, S.C., Pinkston, K.L., Azhdarinia, A., Harvey, B.R., Sevick-Muraca, E.M. Tumor Margin Detection Using Quantitative NIRF Molecular Imaging Targeting EpCAM Validated by Far Red Gene Reporter iRFP. Mol Imaging Biol. 15(5):560-8, 2013. PMID:23619897
  • Lu. Y., Darne, C.D., Tan, I.C., Wu, G., Wilganowski, N., Robinson, H., Azhdarinia, A., Zhu, B., Rasmussen, J.C., Sevick-Muraca, E.M. In vivo imaging of orthotopic prostate cancer with far-red gene reporter fluorescence tomography and in vivo and ex vivo validation. J Biomed Opt. 18(10):101305, 2013. PMID:23797877
  • Azhdarinia, A., Daquinag, A.C., Tseng, C., Ghosh, S.C., Ghosh, P., Amaya-Manzanares F., Sevick-Muraca, E.M., Kolonin, M.G.  Probes for targeted brown adipose tissue imaging. Nat Commun. 4:2472, 2013. PMID: 24045463


Figure 1 Summary: Representative multimodality images in a tumor-bearing mouse at 40 h post-injection of 64Cu-labeled mAb7 (A).   Focal tumor signal was visualized by DsRed and NIRF imaging in vivo (circle). Ex vivo imaging on selected tissues showed comparable fluorescence levels in the kidneys and tumor with low signal elsewhere. Quantification of 64Cu-mAb7 uptake is represented in (B) and indicates highest signal in liver, tumor, and kidneys. Arrow indicates excised tumor. K = kidney, Lu = lung, H = heart, M = muscle.  Scale bar = 1.6 cm. (from Ghosh, S.C. et al., J Med Chem, 56(2):406-16, 2013).

FIGURE 1

: Representative multimodality images in a tumor-bearing mouse

 

 

 

 

 

 

 

 

 

 


 

Figure 2 Summary: Biodistribution of PEP3 conjugated with a NIR fluorophore. (b) Whole-body NIR fluorescence imaging of cold acclimated mice 4 and 24 hrs after iv administration of indicated doses of IRDye800-conjugated PEP3 or control PEP1. Arrows: interscapular signal; arrowheads: perirenal signal. Insets show black/white photographs of mice that had skin removed from the back for imaging. (adapted from Azhdarinia, A. et al., Nat Commun. 4:2472, 2013).

FIGURE 2

Biodistribution of PEP3 conjugated with a NIR fluorophore