Multimodal imaging guided preclinical trials of vascular targeting in prostate cancer

James Kalmuk, Margaret Folaron, Julian Buchinger, Roberto Pili, Mukund Seshadri

Research output: Contribution to journalArticle

Abstract

The high mortality rate associated with castration-resistant prostate cancer (CRPC) underscores the need for improving therapeutic options for this patient population. The purpose of this study was to examine the potential of vascular targeting in prostate cancer. Experimental studies were carried out in subcutaneous and orthotopic Myc-CaP prostate tumors implanted into male FVB mice to examine the efficacy of a novel microtubule targeted vascular disrupting agent (VDA), EPC2407 (Crolibulin™). A non-invasive multimodality imaging approach based on magnetic resonance imaging (MRI), bioluminescence imaging (BLI), and ultrasound (US) was utilized to guide preclinical trial design and monitor tumor response to therapy. Imaging results were correlated with histopathologic assessment, tumor growth and survival analysis. Contrast-enhanced MRI revealed potent antivascular activity of EPC2407 against subcutaneous and orthotopic Myc-CaP tumors. Longitudinal BLI of Myc-CaP tumors expressing luciferase under the androgen response element (Myc- CaP/ARE-luc) revealed changes in AR signaling and reduction in intratumoral delivery of luciferin substrate following castration suggestive of reduced blood flow. This reduction in blood flow was validated by US and MRI. Combination treatment resulted in sustained vascular suppression, inhibition of tumor regrowth and conferred a survival benefit in both models. These results demonstrate the therapeutic potential of vascular targeting in combination with androgen deprivation against prostate cancer.

Original languageEnglish (US)
Pages (from-to)24376-24392
Number of pages17
JournalOncotarget
Volume6
Issue number27
DOIs
StatePublished - 2015
Externally publishedYes

Fingerprint

Multimodal Imaging
Blood Vessels
Prostatic Neoplasms
Neoplasms
Castration
Magnetic Resonance Imaging
Androgens
Response Elements
Therapeutics
Survival Analysis
Luciferases
Microtubules
Prostate
Ultrasonography
Survival
Mortality
Growth
Population

Keywords

  • Androgen deprivation therapy
  • Angiogenesis
  • Multimodality imaging
  • Prostate cancer
  • Vascular disrupting agents

ASJC Scopus subject areas

  • Oncology

Cite this

Kalmuk, J., Folaron, M., Buchinger, J., Pili, R., & Seshadri, M. (2015). Multimodal imaging guided preclinical trials of vascular targeting in prostate cancer. Oncotarget, 6(27), 24376-24392. https://doi.org/10.18632/oncotarget.4463

Multimodal imaging guided preclinical trials of vascular targeting in prostate cancer. / Kalmuk, James; Folaron, Margaret; Buchinger, Julian; Pili, Roberto; Seshadri, Mukund.

In: Oncotarget, Vol. 6, No. 27, 2015, p. 24376-24392.

Research output: Contribution to journalArticle

Kalmuk, J, Folaron, M, Buchinger, J, Pili, R & Seshadri, M 2015, 'Multimodal imaging guided preclinical trials of vascular targeting in prostate cancer', Oncotarget, vol. 6, no. 27, pp. 24376-24392. https://doi.org/10.18632/oncotarget.4463
Kalmuk, James ; Folaron, Margaret ; Buchinger, Julian ; Pili, Roberto ; Seshadri, Mukund. / Multimodal imaging guided preclinical trials of vascular targeting in prostate cancer. In: Oncotarget. 2015 ; Vol. 6, No. 27. pp. 24376-24392.
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