Department of Radiology
The Naga Vara Kishore Pillarsetty Lab
Targeted Theranostics Laboratory
Molecularly targeted therapy modulates a dysregulated target(s) and/or biologic pathway(s) that provides survival advantage for cancer cells. This targeting enables achieve selective destruction of cancer cells while minimizing harm to normal cells. We work on the development and clinical translation of molecular imaging and therapeutic agents that can 1) identify dysregulated pathways noninvasively; 2) serve as prognostic indicators of response and/or monitor response to therapy; 3) aid in understanding drug pharmacokinetics; and 4) take advantage of target overexpression to develop companion radiotherapeutics. The molecular imaging agent can be a small molecule, peptide, antibody, or a nanoparticle and conjugated to a radioactive or optically active or therapeutic payload depending on the intended application. We have leveraged targets such as PSMA, epichaperome, PARP, NaV1.7, and GLP1R to develop targeted theranostics. By collaborating with other laboratories and clinicians at Memorial Sloan Kettering Cancer Center, we have been able to translate several molecular imaging agents for first-in-human studies; These include epichaperome-specific PET probes [124I]-PU-H71 (Pillarsetty et al. 2019, NCT01269593, NCT01393509) and [124I]-PU-AD (Bolaender et al. 2021, NCT03371420), PARP-specific fluorescent intraoperative probe PARPi-FL (Kossatz et al 2020, NCT03085147), and several other PET probes that have entered clinical trials at MSKCC. In addition, we are actively exploring new targets that include mucins, ATM, ATR, DLL3 etc. to develop novel targeted theranostics.
Kalidindi TM, Lee SG, Jou K, Chakraborty G, Skafida M, Tagawa ST, Bander NH, Schoder H, Bodei L, Pandit-Taskar N, Lewis JS, Larson SM, Osborne JR, Pillarsetty NVK. A simple strategy to reduce the salivary gland and kidney uptake of PSMA-targeting small molecule radiopharmaceuticals. Eur J Nucl Med Mol Imaging. 2021 Jul;48(8):2642-2651. doi: 10.1007/s00259-020-05150-w. Epub 2021 Jan 25.
Pillarsetty N, Jhaveri K, Taldone T, Caldas-Lopes E, Punzalan B, Joshi S, Bolaender A, Uddin MM, Rodina A, Yan P, Ku A, Ku T, Shah SK, Lyashchenko S, Burnazi E, Wang T, Lecomte N, Janjigian Y, Younes A, Batlevi CW, Guzman ML, Roboz GJ, Koziorowski J, Zanzonico P, Alpaugh ML, Corben A, Modi S, Norton L, Larson SM, Lewis JS, Chiosis G, Gerecitano JF, Dunphy MPS. Paradigms for Precision Medicine in Epichaperome Cancer Therapy. Cancer Cell. 2019 Nov 11;36(5):559-573.e7. doi: 10.1016/j.ccell.2019.09.007. Epub 2019 Oct 24. PMCID: PMC6996250.
Gangangari KK, Humm JL, Larson SM, Pillarsetty NVK. TMSOTf assisted synthesis of 2’-deoxy-2’-[18F]fluoro-β-D-arabinofuranosylcytosine ([18F]FAC). PLoS One. 2018 May 1;13(5):e0196784. doi: 10.1371/journal.pone.0196784. PMCID: PMC5929562.
Carney B, Kossatz S, Lok BH, Schneeberger V, Gangangari KK, Pillarsetty NVK, Weber WA, Rudin CM, Poirier JT, Reiner T. Target engagement imaging of PARP inhibitors in small-cell lung cancer. Nat Commun. 2018 Jan 12;9(1):176. doi: 10.1038/s41467-017-02096-w. PMCID: PMC5766608.
Dunphy MPS, Pressl C, Pillarsetty N, Grkovski M, Modi S, Jhaveri K, Norton L, Beattie BJ, Zanzonico PB, Zatorska D, Taldone T, Ochiana SO, Uddin MM, Burnazi EM, Lyashchenko SK, Hudis CA, Bromberg J, Schöder HM, Fox JJ, Zhang H, Chiosis G, Lewis JS, Larson SM. First-in-Human Trial of Epichaperome-Targeted PET in Patients with Cancer. Clin Cancer Res. 2020 Oct 1;26(19):5178-5187. doi: 10.1158/1078-0432.CCR-19-3704. Epub 2020 May 4. PMCID: PMC7541604.
Naga Vara Kishore Pillarsetty, PhD
- The Pillarsetty Laboratory develops bioactive radiopharmaceuticals and fluorophores for molecular characterization and targeted treatment of cancer.
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