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

Trial Summary

What is the purpose of this trial?

This pilot clinical trial studies how well magnetic resonance spectroscopic imaging (MRSI) with hyperpolarized carbon 13 (13C) pyruvate alone or in combination with 13C 15N2 Urea works in finding prostate cancer that exhibits poorly differentiated or undifferentiated cells (high-grade) and that is restricted to the site of origin, without evidence of spread (localized) in patients undergoing radical prostatectomy. Diagnostic procedures, such as MRSI with hyperpolarized carbon (13C) pyruvate, may aid in the diagnosis of prostate cancer and in discriminating high-grade from low-grade prostate cancer and benign adjacent prostate tissue

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 data supports the effectiveness of the treatment Hyperpolarized 13C,15N2-urea, Pyruvate (13C) for prostate cancer?

Research shows that using hyperpolarized 13C-pyruvate in imaging can help detect and assess prostate cancer by highlighting changes in tumor metabolism. This technique has been effective in identifying high-grade prostate cancer by measuring increased levels of lactate, a byproduct of cancer cell metabolism, which suggests it could be useful for diagnosing and monitoring treatment response. ^{1 2 3 4 5}

Is hyperpolarized 13C-pyruvate MRI safe for use in humans?

In a study involving 31 patients with prostate cancer, hyperpolarized 13C-pyruvate was used without any dose-limiting toxicities, indicating it is generally safe for human use. ^{1 2 3 5 6}

How does MR Imaging with Pyruvate differ from other prostate cancer treatments?

MR Imaging with Pyruvate is unique because it uses hyperpolarized 13C-pyruvate to provide real-time imaging of metabolic activity in prostate cancer, offering a non-invasive way to assess tumor metabolism and potentially detect cancer more accurately than traditional imaging methods. ^{1 2 3 5 7}

Research Team

Ivan de Kouchkovsky, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

Bilirubin < 1.5 x upper limit of normal (ULN) (unless Gilbert's is suspected)

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

I am fully active or restricted in physically strenuous activity but can do light work.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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]

References

1. England 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. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading. [2018]

3. England 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. [2021]

4. Switzerland 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. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Metabolic imaging of patients with prostate cancer using hyperpolarized [1-¹³C]pyruvate. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1. [2021]

7. China pubmed.ncbi.nlm.nih.gov

Kinetic and perfusion modeling of hyperpolarized (13)C pyruvate and urea in cancer with arbitrary RF flip angles. [2021]