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00085472can140018-sup-125096_1_supp_2544525_n825p4.pptx (4.45 MB)

Supplemental Figures S1-S8 from AEG-1 Promoter–Mediated Imaging of Prostate Cancer

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posted on 2023-03-30, 22:44 authored by Akrita Bhatnagar, Yuchuan Wang, Ronnie C. Mease, Matthew Gabrielson, Polina Sysa, Il Minn, Gilbert Green, Brian Simmons, Kathleen Gabrielson, Siddik Sarkar, Paul B. Fisher, Martin G. Pomper

S1: Schematic maps of AEG-Prom and PEG-Prom reporter constructs S2: c-MYC protein levels analyzed in prostate cancer cell lines by western blotting using anti-MYC antibody (57-70 kDa) S3: Time course for model maturation with PC3-ML-Luc cells using bioluminescence imaging (BLI) at week 5 after injection of: (A) 5 x 104 cells (intracardiac); (B) 1 x 106 cells (tail vein) S4: Cancer-specific AEG-Prom and PEG-Prom activity shown by bioluminescence imaging (BLI) in an experimental model of human prostate cancer (PC3-ML) S5: Comparison of Luc plasmid delivery to lungs of the PCa group for pAEG-Luc treated and pPEG-Luc treated animals (n = 3, PCa-1-3 in Supplemental Fig. S4), respectively S6: Correlation between AEG-1 promoter-driven Luc expression and metastatic sites by histopathological analysis in a bone metastatic prostate cancer model of prostate cancer metastasis S7: Cancer-Specific AEG-Prom activity shown by bioluminescence imaging (BLI) in experimental models of human prostate cancer (PC3-ML) S8: AEG-Prom-based SPECT/CT imaging detects distant metastasis not identified by NaF- or FDG-PET/CT

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ARTICLE ABSTRACT

We describe a new imaging method for detecting prostate cancer, whether localized or disseminated and metastatic to soft tissues and bone. The method relies on the use of imaging reporter genes under the control of the promoter of AEG-1 (MTDH), which is selectively active only in malignant cells. Through a systemic, nanoparticle-based delivery of the imaging construct, lesions can be identified through bioluminescence imaging and single-photon emission computed tomography in the PC3-ML murine model of prostate cancer at high sensitivity. This approach is applicable for the detection of prostate cancer metastases, including bone lesions for which there is no current reliable agent for noninvasive clinical imaging. Furthermore, the approach compares favorably with accepted and emerging clinical standards, including PET with [18F]fluorodeoxyglucose and [18F]sodium fluoride. Our results offer a preclinical proof of concept that rationalizes clinical evaluation in patients with advanced prostate cancer. Cancer Res; 74(20); 5772–81. ©2014 AACR.

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