MRI with Hyperpolarized Bicarbonate for Prostate Cancer

Overseen By Maya Aslam

Age: 18+

Sex: Male

Trial Phase: Phase < 1

Sponsor: Robert Flavell, MD, PhD

Must not be taking: Carbonic anhydrase inhibitors

Disqualifiers: Poorly controlled hypertension, Congestive heart failure, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging method for prostate cancer using a special compound called hyperpolarized bicarbonate (13C). The goal is to determine if this method safely and effectively shows acidity levels in prostate tissue, potentially enhancing cancer understanding. The trial includes individuals with confirmed prostate cancer who plan to undergo surgery soon. Participants will receive an injection before an MRI scan. This study could benefit those interested in advancing prostate cancer diagnostics while gaining a closer look at their condition. As an Early Phase 1 trial, this research focuses on understanding how the new imaging method works in people, offering participants a chance to explore this innovative diagnostic approach.

Will I have to stop taking my current medications?

The trial requires that you stop taking carbonic anhydrase inhibitors, such as acetazolamide, dichlorphenamide, or methazolamide. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

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

Research has shown that hyperpolarized 13C bicarbonate is generally safe for people. Studies have demonstrated that doctors can inject this contrast agent into humans without causing serious side effects. It is used with MRI scans to help visualize acidity levels in body tissues. These findings suggest that the treatment is well-tolerated, but further research is needed to confirm these results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about using hyperpolarized bicarbonate (13C) with MRI for prostate cancer because it offers a unique way to visualize tumor metabolism in real-time. Unlike standard treatments, such as surgery or radiation, which focus on removing or destroying cancer cells, this approach provides detailed insights into how aggressive a tumor might be by looking at its chemical processes. This novel imaging technique could help doctors make better, more personalized treatment decisions by identifying which cancers are more likely to respond to specific therapies.

What evidence suggests that hyperpolarized bicarbonate (13C) might be an effective treatment for prostate cancer?

Research has shown that a new imaging method using hyperpolarized bicarbonate (13C), which participants in this trial will receive, could help detect prostate cancer. Early studies suggest this technology highlights the acidity in tumor tissues, making cancerous areas stand out more clearly. Initial human trials confirmed that this method is safe and may effectively image prostate cancer. This advancement could significantly improve how doctors understand and treat prostate cancer by allowing them to see the cancer more clearly and make better treatment decisions. ^{3 4 5 6 7}

Who Is on the Research Team?

Robert Flavell, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Men over 18 with localized prostate cancer confirmed by biopsy, who are fit (ECOG status of 0 or 1), and have adequate organ function. They must understand the study and consent to participate. Excluded are those with prior prostate cancer treatments like cryosurgery or radiotherapy, inability to undergo MRI, latex allergy, certain medication use, metallic implants affecting MR imaging quality, uncontrolled high blood pressure, significant heart conditions or recent heart attack.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

My tumor is at least 1.0 cm big on an MRI or ultrasound, or I had a positive biopsy with at least 3 cores.

Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) <=1.5 X institutional upper limit of normal

Exclusion Criteria

My blood pressure is higher than 160/100 despite treatment.

I have had treatments like cryosurgery or radiotherapy for prostate cancer but not TURP.

Patients unwilling or unable to undergo MR imaging, including patients with contraindications to Magnetic resonance imaging (MRI) as per UCSF radiology departmental guidelines

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an infusion of hyperpolarized 13C bicarbonate followed by MR imaging with an endorectal coil

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the hyperpolarized 13C bicarbonate injection

5-9 days

Routine and safety assessments

What Are the Treatments Tested in This Trial?

Interventions

• Hyperpolarized Bicarbonate (13C)
• Magnetic Resonance Imaging

Trial Overview The trial is testing a new method using hyperpolarized bicarbonate (13C) injections followed by MRI scans to measure pH levels in prostate tissue before surgery. It's a small-scale pilot study at UCSF for men scheduled for radical prostatectomy within 12 weeks after the imaging tests.

How Is the Trial Designed?

Group I: Pre-surgical participants with prostate cancer Experimental Treatment 2 Interventions

The hyperpolarized 13C bicarbonate injection includes the administration of 35 mL injected intravenously (IV) at a rate of 5 mL/second followed by a 20 mL saline flush at 5 mL/second, followed by magnetic resonance (MR) imaging. The intervention will include routine and safety assessments 5 to 9 days after the injection.

Who Is Running the Clinical Trial?

Robert Flavell, MD, PhD

Lead Sponsor

Trials

5

Recruited

90+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

U.S. Army Medical Research Acquisition Activity

Collaborator

Trials

26

Recruited

10,500+

Published Research Related to This Trial

A new method was developed to simultaneously polarize multiple 13C-enriched metabolites, including sodium bicarbonate and pyruvate, allowing for detailed in vivo analysis of metabolic pathways and pH levels in tumors.

Initial studies in a prostate cancer model showed that this technique can effectively measure tumor metabolism and pH, revealing higher lactate levels and lower pH in tumors compared to normal tissues, indicating its potential for non-invasive cancer diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-compound polarization by DNP allows simultaneous assessment of multiple enzymatic activities in vivo. Wilson, DM., Keshari, KR., Larson, PE., 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]

A new hyperpolarization technique using carbonate precursors can produce high concentrations of hyperpolarized (13)C bicarbonate, which is biocompatible and low in toxicity.

This method allows for enhanced (13)C pH imaging, demonstrating significant signal gains in both phantom studies and in vivo tests on a mouse model of prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic nuclear polarization of biocompatible (13)C-enriched carbonates for in vivo pH imaging. Korenchan, DE., Flavell, RR., Baligand, C., et al.[2023]

Hyperpolarized 13C MRI has shown promise in providing unique metabolic insights into cancer, with a dose-ranging study confirming its safety and feasibility in patients with prostate cancer.

Ongoing research is exploring the use of hyperpolarized agents in various cancer types, and advancements in technology and collaboration among academia, industry, and government are essential for translating this imaging technique into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C MRI: Path to Clinical Translation in Oncology. Kurhanewicz, J., Vigneron, DB., Ardenkjaer-Larsen, JH., et al.[2023]

The study demonstrated that hyperpolarized carbon-13 (HP-13C) metabolic imaging is safe and well-tolerated in pediatric patients with brain tumors, with no adverse events reported during the imaging process.

HP-13C imaging successfully showed the brain's metabolism of HP [1-13C]pyruvate, indicating its potential as a useful tool for assessing metabolic changes in pediatric CNS tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers. Autry, AW., Park, I., Kline, C., et al.[2022]

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]

A new hyperpolarized carbon-13 MRI method has been developed to accurately image the extracellular pH of prostate tumors, which can help detect aggressive forms of prostate cancer and assist in risk stratification.

This method has been validated in preclinical studies and is now ready for human trials, with the potential to improve prostate cancer management by providing a reliable imaging biomarker for tumor acidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinically Translatable Hyperpolarized 13C Bicarbonate pH Imaging Method for Use in Prostate Cancer. Mu, C., Liu, X., Kim, Y., et al.[2023]

Hyperpolarized carbon 13 MRI (13C MRI) is a groundbreaking imaging technique that allows for real-time, noninvasive observation of tissue metabolism, particularly useful in cancer research.

This method has shown promise in clinical applications such as tumor grading, tailoring treatment based on metabolic profiles, and detecting early treatment responses by monitoring metabolic changes before structural alterations in tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon 13 MRI: Clinical Applications and Future Directions in Oncology. Deen, SS., Rooney, C., Shinozaki, A., et al.[2023]

Hyperpolarized 13C-MRI has been developed to monitor metabolic activity in prostate cancer, allowing for the identification of high-grade tumors and assessment of treatment responses.

New PET radiotracers have been introduced that can help distinguish between different subtypes of advanced prostate cancer, showcasing advancements in imaging technology for better patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The changing role of imaging in clinical care. Aggarwal, R., Kurhanewicz, J.[2021]

This study demonstrates that hyperpolarized (HP) (13)C MR spectroscopy can effectively track metabolic changes in prostate cancer, showing increased pyruvate to lactate flux in malignant tissue compared to benign tissue, which correlates with specific metabolic markers.

The research provides the first mechanistic evidence that HP (13)C lactate can serve as a biomarker for prostate cancer in living human tissues, paving the way for better identification of cancer presence and aggressiveness in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic reprogramming and validation of hyperpolarized 13C lactate as a prostate cancer biomarker using a human prostate tissue slice culture bioreactor. Keshari, KR., Sriram, R., Van Criekinge, M., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10683509/

Clinically Translatable Hyperpolarized 13C Bicarbonate pH ... The results demonstrated that we can routinely produce a highly polarized and safe HP H13CO3– contrast agent suitable for human injection.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05851365

Magnetic Resonance (MR) Imaging With Hyperpolarized ... This is a single site, prospective pilot study to determine the feasibility and safety of the administration of HP 13C bicarbonate in 10 patients with prostate ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4349324/

Hyperpolarized 13C MR for Molecular Imaging of Prostate ... The recent first-in-man hyperpolarized 13C MR imaging study in prostate cancer patients has confirmed the clinical potential of this remarkable technology (1).

4. pubs.acs.org pubs.acs.org/doi/10.1021/acssensors.3c00851

Clinically Translatable Hyperpolarized 13 C Bicarbonate pH ... We developed a hyperpolarized carbon-13 MRI method to image the tumor extracellular pH (pH e ) and prepared it for clinical translation for detection and risk ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-03218

Magnetic Resonance Imaging with Hyperpolarized 13C ... This early phase I trial tests the safety and side effects of hyperpolarized 13C bicarbonate prior to magnetic resonance imaging (MRI) in measuring tissue ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37878761/

Clinically Translatable Hyperpolarized 13C Bicarbonate pH ... The results demonstrated that we can routinely produce a highly polarized and safe HP H13CO3- contrast agent suitable for human injection.

7. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05851365

Magnetic Resonance (MR) Imaging With Hyperpolarized ... This is a single site, prospective pilot study to determine the feasibility and safety of the administration of HP 13C bicarbonate in 10 ...