MR Imaging with Pyruvate for Prostate Cancer

(pyruvate Trial)

Overseen By Louise Magat

Age: 18+

Sex: Male

Trial Phase: Phase < 1

Sponsor: University of California, San Francisco

Must not be taking: Androgen deprivation therapy

Disqualifiers: Under 18, MRI contraindications, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how effectively a special MRI technique, using hyperpolarized carbon (13C) pyruvate, detects high-grade prostate cancer confined to the prostate. Researchers will test this imaging method on two groups: those scheduled for prostate surgery and those who have undergone high-intensity focused ultrasound (HIFU) treatment. Men with biopsy-confirmed prostate cancer who are planning surgery or have completed HIFU therapy may be suitable candidates for this trial. The goal is to enhance the diagnosis of aggressive prostate cancers and differentiate them from less severe cases.

As an Early Phase 1 trial, this research focuses on understanding how this innovative imaging technique functions in people, offering participants the chance to contribute to groundbreaking advancements in cancer diagnosis.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on androgen deprivation therapy or a 5-alpha reductase inhibitor, you must stop these at least one month or 14 days before the study, depending on the cohort.

What prior data suggests that this imaging technique is safe for prostate cancer patients?

Research has shown that hyperpolarized [1-13C]pyruvate is generally safe and well-tolerated for imaging. Studies have found it can be used in prostate cancer patients without causing major side effects. In earlier studies, patients handled the treatment well, with no serious problems reported.

For hyperpolarized [13C,15N2]urea, animal research suggests it is safe for studying tumor conditions, such as low oxygen levels in tissues, known as hypoxia. Although this research comes from animal studies, the results support its safety and effectiveness.

Both treatments are in the early testing stages for imaging prostate cancer. They are still under close study for safety, but current data appears promising. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses hyperpolarized 13C-pyruvate and hyperpolarized 13C,15N2-urea to improve MRI imaging for prostate cancer. Unlike typical imaging techniques, this method allows for a detailed view of the tumor's metabolism and blood flow in real-time. This means doctors might get a clearer picture of the cancer's behavior, potentially leading to more precise treatment planning. By enhancing the imaging resolution, the trial aims to provide insights that could improve diagnosis and treatment outcomes for prostate cancer patients.

What evidence suggests that this imaging technique is effective for detecting prostate cancer?

This trial will study a special imaging technique using hyperpolarized 13C-pyruvate to detect prostate cancer by highlighting areas with high energy use, a sign of cancer activity. Participants in Cohort A, pre-surgical prostate cancer patients, and Cohort B, post-HIFU participants, will receive an infusion of hyperpolarized 13C-pyruvate alone or combined with hyperpolarized 13C,15N2-urea. This method can also predict treatment effectiveness by focusing on how cancer cells obtain energy. By combining hyperpolarized 13C-pyruvate with 13C,15N2-urea, doctors can observe changes in energy use and blood flow in the tissue, providing a clearer picture of the cancer's behavior. Early research suggests this combined approach is promising for distinguishing between more aggressive and less aggressive prostate cancer. These methods are still under study but offer a non-invasive way to better understand and diagnose prostate cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Ivan de Kouchkovsky, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for men with biopsy-proven prostate cancer who are planning a radical prostatectomy at UCSF within 12 weeks. They must have good blood counts, liver and kidney function, and be able to undergo MRI/MRSI. Men with severe allergies, heart conditions, or those unable to give consent are excluded.

Inclusion Criteria

The subject is able and willing to comply with study procedures and provide signed and dated informed consent

Hemoglobin >= 9.0 mg/dL

Platelets >= 75,000 cells/uL

Exclusion Criteria

I cannot have certain rectal procedures due to past surgery or allergies.

I have heart failure or my condition limits my physical activity.

I have a history of heart issues but not recent heart attacks or uncontrolled heart rhythm problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Treatment

Participants receive hyperpolarized 13C-pyruvate or co-polarized 13C pyruvate and 13C, 15N2 urea intravenously and undergo MRSI within 12 weeks of radical prostatectomy or biopsies

12 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging and treatment

24 hours

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Hyperpolarized 13C,15N2-urea
• Pyruvate (13C)

Trial Overview The study tests if Magnetic Resonance Spectroscopic Imaging (MRSI) using hyperpolarized carbon C13 pyruvate can accurately identify high-grade localized prostate cancer in patients scheduled for surgery.

How Is the Trial Designed?

Group I: Cohort B: Post-HIFU Participants Experimental Treatment 0 Interventions

Participants will receive an infusion of hyperpolarized 13C-pyruvate alone or co-hyperpolarized 13C pyruvate with hyperpolarized 13C, 15N urea injection prior to metabolic/perfusion high spatial resolution MRI/1H MRSI staging exam (PROSE) with endorectal coil using both a phased-array abdominal coil and an endorectal coil will be performed for participants with planned post-HIFU surveillance systematic and MR-targeted non-investigational biopsies

Group II: Cohort A: Pre-surgical Prostate Cancer patients Experimental Treatment 0 Interventions

Participants will receive an infusion of hyperpolarized 13C-pyruvate alone or co-hyperpolarized 13C pyruvate with hyperpolarized 13C, 15N urea injection prior to metabolic/perfusion high spatial resolution MRI/1H MRSI staging exam (PROSE) with endorectal coil using both a phased-array abdominal coil and an endorectal coil will be performed within 12 weeks of subsequent non-investigational radical prostatectomy.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Ivan de Kouchkovsky, MD

Lead Sponsor

Trials

3

Recruited

190+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

American Cancer Society, Inc.

Collaborator

Trials

237

Recruited

110,000+

National Institute for Biomedical Imaging and Bioengineering (NIBIB)

Collaborator

Trials

102

Recruited

21,600+

Published Research Related to This Trial

Hyperpolarized 13C magnetic resonance spectroscopy can effectively distinguish between high-grade and low-grade prostate cancer by measuring increased lactate production, which is linked to higher levels of lactate dehydrogenase (LDH) activity and monocarboxylate transporter 4 (MCT4) expression in high-grade tumors.

In a study using cultured prostate tissues, significant differences in lactate efflux were observed, indicating that this non-invasive imaging technique could help identify aggressive prostate cancer, potentially improving patient management and treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elevated Tumor Lactate and Efflux in High-grade Prostate Cancer demonstrated by Hyperpolarized 13C Magnetic Resonance Spectroscopy of Prostate Tissue Slice Cultures. Sriram, R., Van Criekinge, M., DeLos Santos, J., et al.[2020]

This study demonstrates that hyperpolarized (13)C-labeled pyruvate can effectively differentiate between various histologic grades of prostate cancer in a mouse model, with significant increases in hyperpolarized lactate levels correlating with cancer progression.

Elevated levels of hyperpolarized lactate, along with total hyperpolarized carbon (THC) and alanine, serve as promising noninvasive biomarkers for detecting prostate cancer and assessing its severity, potentially enhancing future imaging techniques in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading. Albers, MJ., Bok, R., Chen, AP., et al.[2018]

Hyperpolarized 13C-pyruvate MRI successfully detected high rates of glycolytic metabolism in metastatic prostate cancer, with specific kPL values indicating metabolic activity in bone and liver metastases.

The study demonstrated that HP 13C-pyruvate MRI can measure changes in metabolism over time, showing a decrease in kPL values in response to chemotherapy, suggesting its potential as a tool for monitoring treatment efficacy in advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C-pyruvate MRI detects real-time metabolic flux in prostate cancer metastases to bone and liver: a clinical feasibility study. Chen, HY., Aggarwal, R., Bok, RA., et al.[2021]

This study found that aggressive prostate cancer cells (PC3) showed significantly higher uptake of [18F]FDG compared to less aggressive cells (LNCaP), indicating that PET imaging can effectively differentiate between cancer aggressiveness.

Despite similar rates of pyruvate to lactate conversion in both cell types, a negative correlation was observed between [18F]FDG uptake and the rate of this conversion, suggesting that metabolic pathways in prostate cancer may differ from other tumors and highlighting the potential of combining imaging techniques for better diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyruvate-lactate exchange and glucose uptake in human prostate cancer cell models. A study in xenografts and suspensions by hyperpolarized [1-13 C]pyruvate MRS and [18 F]FDG-PET. van Heijster, FHA., Heskamp, S., Breukels, V., et al.[2021]

Hyperpolarized magnetic resonance imaging (MRI) of pyruvate metabolism shows consistent delivery and conversion in patients with primary prostate cancer, indicating its potential reliability for metabolic imaging.

The study found that higher lactate levels correlate with more aggressive cancer (higher Gleason grade) and are associated with specific genomic alterations, such as PTEN loss, suggesting a link between cancer genetics and metabolic changes that could inform treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1. Granlund, KL., Tee, SS., Vargas, HA., et al.[2021]

MRI using hyperpolarized agents can effectively differentiate cancerous tissues from healthy ones by measuring the conversion rate of pyruvate to lactate, which is significantly higher in tumors (Kpl = 0.050 for prostate and 0.052 for liver tumors) compared to healthy tissues (Kpl = 0.028).

The study also found that cancerous tissues exhibit significantly higher pyruvate perfusion compared to urea perfusion, indicating increased metabolic activity and blood supply in tumors, which could aid in better monitoring and treatment response assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetic and perfusion modeling of hyperpolarized (13)C pyruvate and urea in cancer with arbitrary RF flip angles. Bahrami, N., Swisher, CL., Von Morze, C., et al.[2021]

The study demonstrated that hyperpolarized [1-¹³C]pyruvate is safe for use in humans, with no dose-limiting toxicities observed in 31 prostate cancer patients, confirming its potential for noninvasive imaging.

The imaging technique successfully detected elevated levels of [1-¹³C]lactate in tumor regions, indicating its effectiveness in characterizing tumor metabolism and potentially aiding in cancer diagnosis and treatment monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic imaging of patients with prostate cancer using hyperpolarized [1-¹³C]pyruvate. Nelson, SJ., Kurhanewicz, J., Vigneron, DB., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7984723/

Hyperpolarized [1-13C]-Pyruvate Magnetic Resonance ... Conclusions: Hyperpolarized [1-13C]-pyruvate MRSI of prostate cancer predicts efficacy of targeting the Warburg effect. Introduction.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e15059

Correlating survival outcomes in patients with advanced ... Correlating survival outcomes in patients with advanced prostate cancer with novel hyperpolarized 13C MRI metabolic imaging biomarkers.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31685983/

Hyperpolarized 13 C-pyruvate MRI detects real-time metabolic ... Results: We observed a high rate of glycolytic metabolism in prostate cancer metastases, with a mean kPL value of 0.020 ± 0.006 (s-1) and 0.026 ± 0.000 (s-1) ...

4. analyticalsciencejournals.onlinelibrary.wiley.com analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/nbm.3997

Investigation of analysis methods for hyperpolarized 13C ... MRI using hyperpolarized (HP) carbon-13 pyruvate is being investigated in clinical trials to provide non-invasive measurements of metabolism ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1476558618304056

Hyperpolarized (13)C MRI: path to clinical translation in ... A dose-ranging study of HP [1-13C]pyruvate in patients with prostate cancer established safety and feasibility of this technique. Additional studies are ongoing ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4201045/

Metabolic Imaging of Patients with Prostate Cancer Using ... This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-13C]pyruvate as an agent for noninvasively characterizing ...

7. dctd.cancer.gov dctd.cancer.gov/drug-discovery-development/reagents-materials/imaging-ind-resources/documentation/13c-pyruvate-clinical.pdf

Summary of Data: Clinical prostate cancer access the safety and tolerability and imaging potential of hyperpolarized [1-13C] pyruvate Injection via 13C imaging (13C MRI) and 13C MR ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03933670

Hyperpolarized Pyruvate (13C) MR Imaging in Monitoring ... This phase II trial studies the side how well hyperpolarized carbon C 13 pyruvate (HP C-13 pyruvate) magnetic resonance imaging (MRI) works in monitoring ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2666441024000207

Dual hyperpolarized [1-13C]pyruvate and [13C]urea ... Hyperpolarized [1-13C]pyruvate MRI was able to detect areas of clinically occult prostate cancer not seen on multiparametric MRI. •. The novel addition of ...

10. nature.com nature.com/articles/s41391-019-0180-z

Hyperpolarized 13 C-pyruvate MRI detects real-time ... HP 13 C-pyruvate MRI can detect real-time glycolytic metabolism within prostate cancer metastases, and can measure changes in quantitative k PL values ...