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Updated: Jun 20, 2026
Hyperpolarized 13C Metabolic Magnetic Resonance Spectroscopy and Imaging
Published on: December 30, 2016
Proton MRS detects metabolic changes in hormone sensitive and resistant human prostate cancer models CWR22 and CWR22r
H Carl Le1, Mihaela Lupu, Khushali Kotedia
1Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. lec@mskcc.org
Abstract:
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.
Insights
17-Allylamino, 17-demethoxygeldanamycin (17-AAG) effectively targets tumor heat shock protein 90 (hsp90), reducing oncogenic proteins and showing promise in prostate cancer. Tumor total choline levels, measured by proton MR spectroscopy, decreased post-treatment, indicating potential as an early biomarker for targeted therapy response.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- 17-Allylamino, 17-demethoxygeldanamycin (17-AAG) is an inhibitor of heat shock protein 90 (hsp90).
- 17-AAG preferentially inhibits tumor hsp90 over normal cells, showing efficacy in various cancers, including hormone-resistant prostate cancer.
- Treatment with 17-AAG reduces critical oncogenic proteins like androgen receptor and HER2/neu, and induces metabolic changes in tumor cells.
Purpose of the Study:
- To investigate the metabolic changes in total choline levels in prostate cancer xenografts following 17-AAG treatment.
- To assess the utility of proton magnetic resonance spectroscopic imaging (MRSI) in detecting these metabolic changes as an early biomarker of treatment response.
Main Methods:
- Proton MR spectroscopy was used to measure total choline distributions in CWR22 (hormone-sensitive) and CWR22r (hormone-resistant) prostate cancer xenograft tumors in mice.
- Measurements were taken before and at 4 h and 48 h after a single-bolus administration of 17-AAG (100 mg/kg).
- Immunohistochemistry and tumor growth inhibition were also assessed.
Main Results:
- Total choline levels significantly declined at 4 h post-treatment in CWR22 tumors (P = 0.001) and at 48 h in CWR22r tumors (P = 0.003).
- Metabolic changes in total choline intensity detected by MRSI correlated with immunohistochemistry findings and tumor growth inhibition in CWR22r (P = 0.01).
- Prostate-specific antigen levels remained constant in control CWR22 but increased in treated CWR22r tumors.
Conclusions:
- Metabolic changes in total choline, detectable by proton MRSI, serve as an early indicator of response to 17-AAG targeted therapy in advanced-stage prostate cancer.
- Proton MRSI can be a valuable non-invasive biomarker for monitoring treatment efficacy.
- These findings support the use of 17-AAG as a targeted therapy for prostate cancer, with MRSI aiding in early response assessment.
