{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T02:01:43Z","timestamp":1787968903156,"version":"build-2784847793"},"reference-count":64,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01CA256740"],"award-info":[{"award-number":["R01CA256740"]}]},{"name":"NIH","award":["R01CA215694"],"award-info":[{"award-number":["R01CA215694"]}]},{"name":"NIH","award":["R01CA238379"],"award-info":[{"award-number":["R01CA238379"]}]},{"name":"NIH","award":["U01EB026412"],"award-info":[{"award-number":["U01EB026412"]}]},{"name":"NIH","award":["P41EB013598"],"award-info":[{"award-number":["P41EB013598"]}]},{"name":"NIH","award":["S10OD025077"],"award-info":[{"award-number":["S10OD025077"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Most of the existing hyperpolarized (HP) 13C MRI analyses use univariate rate maps of pyruvate-to-lactate conversion (kPL), and radiomic-style multiparametric models extracting complex, higher-order features remain unexplored. Purpose: To establish a multivariate framework based on whole abdomen\/pelvis HP 13C-pyruvate MRI and evaluate the association between multiparametric features of metabolism (MFM) and clinical outcome measures in advanced and metastatic prostate cancer. Methods: Retrospective statistical analysis was performed on 16 participants with metastatic or local-regionally advanced prostate cancer prospectively enrolled in a tertiary center who underwent HP-pyruvate MRI of abdomen or pelvis between November 2020 and May 2023. Five patients were hormone-sensitive and eleven were castration-resistant. GMP-grade [1-13C]pyruvate was polarized using a 5T clinical-research DNP polarizer, and HP MRI used a set of flexible vest-transmit, array-receive coils, and echo-planar imaging sequences. Three basic metabolic maps (kPL, pyruvate summed-over-time, and mean pyruvate time) were created by semi-automatic segmentation, from which 316 MFMs were extracted using an open-source, radiomic-compliant software package. Univariate risk classifier was constructed using a biologically meaningful feature (kPL,median), and the multivariate classifier used a two-step feature selection process (ranking and clustering). Both were correlated with progression-free survival (PFS) and overall survival (OS) (median follow-up = 22.0 months) using Cox proportional hazards model. Results: In the univariate analysis, patients harboring tumors with lower-kPL,median had longer PFS (11.2 vs. 0.5 months, p &lt; 0.01) and OS (NR vs. 18.4 months, p &lt; 0.05) than their higher-kPL,median counterparts. Using a hypothesis-generating, age-adjusted multivariate risk classifier, the lower-risk subgroup also had longer PFS (NR vs. 2.4 months, p &lt; 0.002) and OS (NR vs. 18.4 months, p &lt; 0.05). By contrast, established laboratory markers, including PSA, lactate dehydrogenase, and alkaline phosphatase, were not significantly associated with PFS or OS (p &gt; 0.05). Key limitations of this study include small sample size, retrospective study design, and referral bias. Conclusions: Risk classifiers derived from select multiparametric HP features were significantly associated with clinically meaningful outcome measures in this small, heterogeneous patient cohort, strongly supporting further investigation into their prognostic values.<\/jats:p>","DOI":"10.3390\/cancers17132211","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:56:54Z","timestamp":1751353014000},"page":"2211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Multivariate Framework of Metabolism in Advanced Prostate Cancer Using Whole Abdominal and Pelvic Hyperpolarized 13C MRI\u2014A Correlative Study with Clinical Outcomes"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2765-1685","authenticated-orcid":false,"given":"Hsin-Yu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"de Kouchkovsky","sequence":"additional","affiliation":[{"name":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1737-9056","authenticated-orcid":false,"given":"Robert A.","family":"Bok","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA"},{"name":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6878-8189","authenticated-orcid":false,"given":"Michael A.","family":"Ohliger","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8118-3931","authenticated-orcid":false,"given":"Daniel","family":"Gebrezgiabhier","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanner","family":"Nickles","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Carvajal","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy W.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4183-3634","authenticated-orcid":false,"given":"Peder E. Z.","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3544-5339","authenticated-orcid":false,"given":"John","family":"Kurhanewicz","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA"},{"name":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B.","family":"Vigneron","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94158, USA"},{"name":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1016\/S0140-6736(22)00367-1","article-title":"Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): A multicentre, open-label, randomised, phase 3 study with a 2 \u00d7 2 factorial design","volume":"399","author":"Fizazi","year":"2022","journal-title":"Lancet"},{"key":"ref_2","first-page":"891","article-title":"Olaparib for Metastatic Castration-Resistant Prostate Cancer","volume":"383","author":"Kang","year":"2020","journal-title":"Reply. 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