Proton MRS detects metabolic changes in hormone sensitive and resistant human prostate cancer models CWR22 and CWR22r.
17-Allylamino, 17-demethoxygeldanamycin (17-AAG), an effective inhibitor of the heat shock protein hsp90, preferentially inhibiting tumor hsp90 compared to hsp90 from normal cells, has shown promising results against several cancers, including hormone-resistant prostate cancer. Levels of several oncogenic proteins critical to tumor growth and progression, such as androgen receptor and HER2/neu, were reduced 4 h post 17-allylamino, 17-demethoxygeldanamycin treatment. Posttreatment metabolic changes have also been observed in several tumor cell lines. In this study, total choline distributions in hormone sensitive CWR22 and hormone resistant CWR22r prostate cancer xenograft tumors in mice were measured before and at 4 h and 48 h after a single-bolus 17-allylamino, 17-demethoxygeldanamycin treatment at 100 mg/kg, using proton MR spectroscopy. Our results show that tumor total choline levels declined 4 h after the treatment for CWR22 (P = 0.001) and 48 h post treatment for CWR22r (P = 0.003). Metabolic changes, in particular of total choline intensity detected by proton magnetic resonance spectroscopic imaging (MRSI), are consistent with the observed immunohistochemistry changes, tumor growth inhibition for CWR22r (P = 0.01 at 14 days post treatment), and a constant prostate specific antigen level versus increasing prostate specific antigen for control CWR22 (P = 0.01). Metabolic changes in total choline by proton MRSI can be used as an early biomarker of response for advanced-stage prostate cancer in targeted therapy such as 17-allylamino, 17-demethoxygeldanamycin.
Le
H Carl
HC
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. lec@mskcc.org
Lupu
Mihaela
M
Kotedia
Khushali
K
Rosen
Neal
N
Solit
David
D
Koutcher
Jason A
JA
D000728:Androgens / Q000008:administration & dosage* / Q000378:metabolism*; D016227:Benzoquinones / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002794:Choline / Q000378:metabolism*; D006801:Humans; D047029:Lactams, Macrocyclic / Q000008:administration & dosage*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011522:Protons
D000728:Androgens; D016227:Benzoquinones; D014408:Biomarkers, Tumor; D047029:Lactams, Macrocyclic; D011522:Protons; C112765:tanespimycin; D002794:Choline