Characterizing Prostate Tumor Mouse Xenografts with CEST and MT-MRI and Redox Scanning

  • Kejia Cai
  • He N. Xu
  • Anup Singh
  • Mohammad Haris
  • Ravinder Reddy
  • Lin Z. LiEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 765)


The main goal of this study was to use multimodality imaging methods to reveal the heterogeneity in prostate cancer and seek the correlation between the characteristic heterogeneity and tumor aggressiveness. Here we report the preliminary data on chemical exchange saturation transfer (CEST) and magnetization transfer (MT) magnetic resonance imaging (MRI) and redox scanning [cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imaging] of two aggressive human prostate tumor lines (DU-145 and PC-3) xenografted in athymic nude mice. The results obtained by these methods appeared to be consistent, with all showing a higher level of heterogeneity in DU-145 tumors than in PC-3 tumors. DU-145 tumors showed CEST maps with both positive and negative areas while PC-3 CEST maps were relatively homogeneous. The mean CEST value for PC-3, 23.0 ± 2.1 %, is at a significantly higher level (p < 0.05) than DU-145 (1.9 ± 6.7 %) at the peak of the CEST asymmetric curve (+2 ppm). Fp redox ratio (Fp/(NADH + Fp)) images exhibited localized highly oxidized regions in DU-145 tumors, whereas PC-3 tumors appeared to be less heterogeneous. These results suggest a possible role of metabolism in tumor progression. More studies, including an indolent prostate tumor line and with larger sample size, will be performed in the future to identify the biomarkers for prostate tumor aggressiveness.


Mitochondrial redox state Fluorescence imaging Metabolism Tumor aggressiveness 



The authors thank Drs. Weixia Liu and Steve Pickup for their technical assistance with animal MRI scanners. This work was supported by an NIH research resource (P41RR02305, R. Reddy) and the SAIR grant 2U24-CA083105 (J.D. Glickson and L. Chodosh).


  1. 1.
    Jemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69CrossRefPubMedGoogle Scholar
  2. 2.
    Li LZ, Zhou R, Xu HN et al (2009) Quantitative magnetic resonance and optical imaging biomarkers of melanoma metastatic potential. Proc Natl Acad Sci U S A 106:6608–6613CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Li LZ, Zhou R, Zhong T et al (2007) Predicting melanoma metastatic potential by optical and magnetic resonance imaging. Adv Exp Med Biol 599:67–78CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Grossman RI, Gomori JM, Ramer KN et al (1994) Magnetization transfer: theory and clinical applications in neuroradiology. Radiographics 14:279–290CrossRefGoogle Scholar
  5. 5.
    Henkelman RM, Stanisz GJ, Graham SJ (2001) Magnetization transfer in MRI: a review. NMR Biomed 14:57–64CrossRefGoogle Scholar
  6. 6.
    Sun PZ, Zhou J, Sun W et al (2006) Detection of the ischemic penumbra using pH-weighted MRI. J Cereb Blood Flow Metab 27:1129CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Zhou J, Payen JF, Wilson DA et al (2003) Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med 9:1085–1090CrossRefPubMedGoogle Scholar
  8. 8.
    Ling W, Regatte RR, Navon G et al (2008) Assessment of glycosaminoglycan concentration in vivo by chemical exchange-dependent saturation transfer (gagCEST). Proc Natl Acad Sci U S A 105:2266–2270CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    van Zijl PCM, Jones CK, Ren J et al (2007) MRI detection of glycogen in vivo by using chemical exchange saturation transfer imaging (glycoCEST). Proc Natl Acad Sci 104:4359–4364CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Chance B, Schoener B, Oshino R et al (1979) Oxidation–reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals. J Biol Chem 254:4764–4771PubMedPubMedCentralGoogle Scholar
  11. 11.
    Quistorff B, Haselgrove JC, Chance B (1985) High spatial resolution readout of 3-D metabolic organ structure: An automated, low-temperature redox ratio-scanning instrument. Anal Biochem 148:389–400CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Xu HN, Nioka S, Chance B et al (2011) Heterogeneity of mitochondrial redox state in premalignant pancreas in a PTEN null transgenic mouse model. Adv Exp Med Biol 201:207–213CrossRefGoogle Scholar
  13. 13.
    Xu HN, Nioka S, Glickson JD et al (2010) Quantitative mitochondrial redox imaging of breast cancer metastatic potential. J Biomed Opt 15:036010CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Pulukuri SM, Gondi CS, Lakka SS et al (2005) RNA interference-directed knockdown of urokinase plasminogen activator and urokinase plasminogen activator receptor inhibits prostate cancer cell invasion, survival, and tumorigenicity in vivo. J Biol Chem 280:36529–36540CrossRefPubMedGoogle Scholar
  15. 15.
    Haris M, Cai K, Singh A et al (2010) In vivo mapping of brain myo-inositol. Neuroimage 54:2079–2085CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Xu HN, Wu B, Nioka S et al (2009) Calibration of redox scanning for tissue samples. Proc SPIE 7174:71742F1–71742F8Google Scholar
  17. 17.
    Xu HN, Wu B, Nioka S et al (2009) Quantitative redox scanning of tissue samples using a calibration procedure. J Innov Opt Health Sci 2:375–385CrossRefGoogle Scholar
  18. 18.
    van Zijl PCM, Zhou J, Mori N et al (2003) Mechanism of magnetization transfer during on-resonance water saturation. A new approach to detect mobile proteins, peptides, and lipids. Magn Reson Med 49:440CrossRefPubMedGoogle Scholar
  19. 19.
    van Zijl PCM, Yadav NN (2011) Chemical exchange saturation transfer (CEST): what is in a name and what isn’t? Magn Reson Med 65:927CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Woessner DE, Zhang S, Merritt ME et al (2005) Numerical solution of the Bloch equations provides insights into the optimum design of PARACEST agents for MRI. Magn Reson Med 53:790–799CrossRefGoogle Scholar
  21. 21.
    Laniado ME, Lalani EN, Fraser SP et al (1997) Expression and functional analysis of voltage-activated Na+ channels in human prostate cancer cell lines and their contribution to invasion in vitro. Am J Pathol 150:1213–1221PubMedPubMedCentralGoogle Scholar
  22. 22.
    Dai Y, Bae K, Siemann DW (2011) Impact of hypoxia on the metastatic potential of human prostate cancer cells. Int J Radiat Oncol 81:521–528CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Kejia Cai
    • 1
  • He N. Xu
    • 1
  • Anup Singh
    • 1
  • Mohammad Haris
    • 1
  • Ravinder Reddy
    • 1
  • Lin Z. Li
    • 1
    Email author
  1. 1.Department of RadiologyUniversity of PennsylvaniaPhiladelphiaUSA

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