Metabolic Tracers for Kidney Cancer

Overseen By Vitaly Margulis, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Uncontrolled diabetes, Pregnant, others

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

Compensation: Varies

Number of Visits: 1

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to understand the metabolism of cancers involving the kidney, including renal cell carcinomas and urothelial cell carcinomas, and how kidney cancers use different types of fuel to support tumor growth. This study uses specially labeled nutrient tracers of compounds normally found circulating in the blood. The nutrients (glucose, fructose, glutamine, acetate, and lactate) are also found in common foods. A nutrient tracer will be given to the participants through an intravenous (IV) catheter during surgery or biopsy, and blood will be collected every 30 minutes during the infusion to monitor safety parameters and the nutrient tracers. The investigators will collect a tissue sample after the completion of surgery. Participants not having an infusion will have their tissue collected after surgery or biopsy. Participation in this study will not change patient care. All patients will receive standard of care treatment as determined by their doctors.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications. It mentions that participation will not change your standard care, so it's likely you can continue your medications, but you should confirm with the trial team.

Is the use of 13C-labeled metabolic tracers safe for humans?

The research does not provide specific safety data for 13C-labeled metabolic tracers in humans, but these compounds are used in studies to understand tumor metabolism, suggesting they are generally considered safe for research purposes. ^{1 2 3 4 5}

How does the treatment using metabolic tracers for kidney cancer differ from other treatments?

This treatment is unique because it uses hyperpolarized 13C pyruvate magnetic resonance imaging to non-invasively differentiate between benign and malignant kidney tumors by analyzing their metabolic activity, specifically lactate production, which is not possible with conventional imaging methods. ^{1 2 5 6 7}

What data supports the effectiveness of the treatment 13C-Acetate and other Carbon-13 labeled compounds for kidney cancer?

The research does not provide direct evidence supporting the effectiveness of 13C-Acetate or other Carbon-13 labeled compounds for treating kidney cancer. However, studies show that metabolic imaging using hyperpolarized 13C-pyruvate can differentiate between aggressive and less aggressive kidney tumors, suggesting that metabolic tracers can be useful in understanding tumor behavior. ^{1 2 5 8 9}

Who Is on the Research Team?

Vitaly Margulis

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

Adults with probable or confirmed kidney or urothelial cancer needing surgery can join. They must understand and sign consent, and may be in other trials if approved by the lead doctor. Not for those with uncontrolled diabetes (if getting a tracer infusion), pregnant/breastfeeding women, or non-surgical candidates.

Inclusion Criteria

I need a biopsy or surgery for my suspected kidney or bladder cancer.

The willingness to sign and ability to understand a written informed consent.

Subjects of all races and ethnic origins

Exclusion Criteria

Pregnant or breastfeeding

My diabetes is not well-managed.

I cannot have surgery for my condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery/Biopsy and Infusion

Participants undergo surgical resection or biopsy with infusion of 13C-labeled nutrient tracers and blood collection every 30 minutes during the procedure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the procedure

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 13C-Acetate
• 13C-Fructose
• 13C-Glucose
• 13C-Glutamine
• 13C-Lactate

Trial Overview The study is examining how kidney cancers metabolize different nutrients during surgery using labeled tracers like glucose and lactate. Participants will receive these through an IV to track tumor fuel use without affecting their standard treatment.

How Is the Trial Designed?

Group I: 13C-Lactate Experimental Treatment 1 Intervention

Group II: 13C-Glutamine Experimental Treatment 1 Intervention

Group III: 13C-Glucose Experimental Treatment 1 Intervention

Group IV: 13C-Fructose Experimental Treatment 1 Intervention

Group V: 13C-Acetate Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Howard Hughes Medical Institute

Collaborator

Trials

4

Recruited

24,500+

Published Research Related to This Trial

In a study involving 21 patients with suspected kidney tumors, [1-(11)C]acetate (AC) was found to have variable uptake in tumors compared to surrounding kidney tissue, with most tumors showing equal or lower uptake than normal tissue.

The results suggest that AC PET is not effective for characterizing renal masses, as most tumors did not accumulate AC more than the normal kidney parenchyma, limiting its utility in diagnosing renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[1-(11)C]acetate uptake is not increased in renal cell carcinoma. Kotzerke, J., Linné, C., Meinhardt, M., et al.[2018]

A novel magnetic resonance-compatible bioreactor platform was used to study patient-derived renal tumor tissue, revealing that clear cell renal cell carcinomas (ccRCCs) produce more lactate and release it faster than benign tumors.

The increased lactate production in ccRCCs is linked to higher levels of lactate dehydrogenase A and monocarboxylate transporter 4, suggesting that hyperpolarized 13C pyruvate MR could effectively differentiate malignant tumors from benign ones, potentially reducing unnecessary surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive differentiation of benign renal tumors from clear cell renal cell carcinomas using clinically translatable hyperpolarized 13C pyruvate magnetic resonance. Sriram, R., Van Criekinge, M., DeLos Santos, J., et al.[2020]

Metabolic imaging using carbon-13 MRI (HP-13C-MRI) can effectively differentiate aggressive clear cell renal cell carcinoma (ccRCC) from less aggressive tumors, showing a strong correlation between the imaging results and tumor grade.

The study found that higher levels of the pyruvate transporter MCT1, which were linked to tumor aggressiveness, also predicted overall and disease-free survival in patients, suggesting that HP-13C-MRI could be a valuable non-invasive tool for assessing renal cancer aggressiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study. Ursprung, S., Woitek, R., McLean, MA., et al.[2023]

In a study of 100 patients with renal cell carcinoma (RCC), the maximum standard uptake value (SUVmax-T) from 18F-FDG PET/CT was found to be a significant predictor of overall survival, with a cut-off level of 5.4 showing 81% sensitivity and 75% specificity.

The study revealed that while SUVmax-T and cancer staging are important prognostic factors for survival in RCC, factors like gender and pathological subtypes did not significantly affect survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Significance of 18F-FDG PET/CT Imaging in Survival Outcomes in Patients with Renal Cell Carcinoma. Tatar, G., Gündoğan, C., Şahin, ÖF., et al.[2022]

Molecular profiling of clear cell renal cell cancer (ccRCC) has shown significant metabolic reprogramming, with upregulation of genes related to glycolysis, glutamine metabolism, and lipogenesis, which correlates with tumor grade and patient survival.

Preclinical studies suggest that targeting metabolic pathways, such as aerobic glycolysis and fatty acid synthesis, may offer new therapeutic strategies for ccRCC, supported by ongoing phase 1 and 2 clinical trials evaluating these targeted agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel drugs that target the metabolic reprogramming in renal cell cancer. van der Mijn, JC., Panka, DJ., Geissler, AK., et al.[2020]

In a study of 20 patients with suspected renal tumors, (11)C-acetate PET imaging showed a 70% detection rate for renal cell carcinoma, indicating its potential effectiveness as a diagnostic tool.

The study suggests that (11)C-acetate demonstrates significant uptake in renal cell carcinoma, making it a promising PET tracer for detecting this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

11C-Acetate PET imaging for renal cell carcinoma. Oyama, N., Okazawa, H., Kusukawa, N., et al.[2021]

A study involving patients with brain tumors showed that infusing (13)C-enriched acetate prior to surgery led to the production of (13)C-enriched glucose and lactate, indicating active metabolism of acetate in tumors.

The contribution of glucose and lactate synthesis from acetate metabolism in brain tumors was found to be less than 4%, suggesting that direct oxidation of acetate in the citric acid cycle is the primary metabolic pathway in these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic gluconeogenesis influences (13)C enrichment in lactate in human brain tumors during metabolism of [1,2-(13)C]acetate. Pichumani, K., Mashimo, T., Vemireddy, V., et al.[2018]

Patient-derived xenografts (PDX) of clear cell renal cell carcinoma (ccRCC) accurately reflect the imaging and metabolic characteristics of human tumors, making them valuable for preclinical studies.

The study revealed significant metabolic heterogeneity among different PDX models, highlighting the importance of considering metabolic plasticity when using these models for testing new imaging and therapeutic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiparametric Magnetic Resonance Imaging and Metabolic Characterization of Patient-Derived Xenograft Models of Clear Cell Renal Cell Carcinoma. Agudelo, JP., Upadhyay, D., Zhang, D., et al.[2022]

This study demonstrated that pyruvate carboxylase is highly active in the kidney, significantly contributing to renal metabolism, particularly when lactate is used as a substrate.

The research revealed that while the TCA cycle is active, pyruvate cycling and pyruvate dehydrogenase are less active, indicating a complex metabolic compartmentalization in kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isotopomer analyses with the tricarboxylic acid cycle intermediates and exchanging metabolites from the rat kidney. Jin, ES., Wen, X., Malloy, CR.[2023]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

[1-(11)C]acetate uptake is not increased in renal cell carcinoma. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Non-invasive differentiation of benign renal tumors from clear cell renal cell carcinomas using clinically translatable hyperpolarized 13C pyruvate magnetic resonance. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study. [2023]

4. Turkey pubmed.ncbi.nlm.nih.gov

Prognostic Significance of 18F-FDG PET/CT Imaging in Survival Outcomes in Patients with Renal Cell Carcinoma. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Novel drugs that target the metabolic reprogramming in renal cell cancer. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

11C-Acetate PET imaging for renal cell carcinoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Hepatic gluconeogenesis influences (13)C enrichment in lactate in human brain tumors during metabolism of [1,2-(13)C]acetate. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Multiparametric Magnetic Resonance Imaging and Metabolic Characterization of Patient-Derived Xenograft Models of Clear Cell Renal Cell Carcinoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Isotopomer analyses with the tricarboxylic acid cycle intermediates and exchanging metabolites from the rat kidney. [2023]