EVALUATION OF [11C]MPC-6827 AS A MICROTUBULE TARGETING PET RADIOTRACER IN CANCER CELL LINES

Authors

  • J. S. DILEEP KUMAR Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, 1051 Riverside Drive, New York, NY 10032, USA https://orcid.org/0000-0001-6688-3991
  • JAYA PRABHAKARAN Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, 1051 Riverside Drive, New York, NY 10032, USA, Department of Psychiatry, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA
  • NARESH DAMUKA Department of Radiology, Wake Forest School of Medicine, One Medical Center Boulevard, Winston-Salem, NC 27157-1088, USA
  • JUSTIN W. HINES Department of Radiology, Wake Forest School of Medicine, One Medical Center Boulevard, Winston-Salem, NC 27157-1088, USA
  • STEVEN J. KRIDEL Department of Cancer Biology, Wake Forest School of Medicine, One Medical Center Boulevard, Winston-Salem, NC 27157-1088, USA
  • J. JOHN MANN Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, New York, 1051 Riverside Drive, New York, NY 10032, USA, Department of Psychiatry, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA, Department of Radiology, Columbia University Medical Center, 622 West 168th Street, PB-1-301, New York, NY 10032, USA
  • AKIVA MINTZ Department of Radiology, Columbia University Medical Center, 622 West 168th Street, PB-1-301, New York, NY 10032, USA
  • KIRAN KUMAR SOLINGAPURAM SAI Department of Radiology, Wake Forest School of Medicine, One Medical Center Boulevard, Winston-Salem, NC 27157-1088, USA

DOI:

https://doi.org/10.22159/ijpps.2020v12i1.35657

Keywords:

PET, Microtubule, Radiotracer, Cancer, Cytoskeleton

Abstract

Objective: The objective of this study was to evaluate the uptake and specificity of [11C]MPC-6827, a MT targeted PET ligand in prostate, glioblastoma and breast cancer cells.

Methods: [11C]MPC-6827 was synthesized by reacting corresponding desmethyl precursors with [11C]CH3I in a GE-FX2MeI/FX2M radiochemistry module. In vitro binding of [11C]MPC-6827 was performed in breast cancer MDA-MB-231, glioblastoma (GBM) patient-derived tumor (GBM-PDX), GBM U251 and prostate cancer 3 (PC3) cell lines at 37 °C in quadruplicate at 5, 15, 30, 60, and 90 minute incubation time. The nonspecific bindings were determined by incubation with unlabeled microtubule targeting agents MPC-6827, HD-800, colchicine, paclitaxel and docetaxel (5.0 mM).

Results: [11C]MPC-6827 provided the highest binding in the breast cancer cell, MDA-MB-231, among all the cells studied, with 90% specific binding. [11C]MPC-6827 binds to glioblastoma PDX and U251 cells with ~50% and 40% specific binding, whereas, prostate cancer cell line, PC3 cells showed 40% specific binding. [11C]MPC-6827 also exhibits binding to the taxane and colchicine binding sites of MTs, in MDA-MB-231 cells.

Conclusion: These data indicate that [11C]MPC-6827 can be a promising PET radiotracer for preclinical imaging of the brain and peripheral cancers.

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Published

01-01-2020

How to Cite

KUMAR, J. S. D., J. PRABHAKARAN, N. DAMUKA, J. W. HINES, S. J. KRIDEL, J. J. MANN, A. MINTZ, and K. K. SOLINGAPURAM SAI. “EVALUATION OF [11C]MPC-6827 AS A MICROTUBULE TARGETING PET RADIOTRACER IN CANCER CELL LINES:”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 12, no. 1, Jan. 2020, pp. 43-47, doi:10.22159/ijpps.2020v12i1.35657.

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