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?

This trial aims to understand how kidney cancers, such as renal cell and urothelial cell carcinomas, utilize different nutrients for growth. Researchers employ special nutrient tracers, including 13C-Acetate, 13C-Fructose, 13C-Glucose, 13C-Glutamine, and 13C-Lactate, to observe how these cancers process fuels like glucose and fructose. Participants will receive these tracers during surgery, and researchers will collect blood and tissue samples to monitor the process. Individuals with kidney or related cancer who require surgery and are willing to sign a consent form are suitable candidates for this study. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new insights into cancer metabolism.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using 13C-labeled nutrients such as fructose, lactate, glucose, acetate, and glutamine is generally safe for people. These tracers are stable isotopes, meaning they behave like natural substances in the body.

Studies have found that 13C-fructose can safely monitor how the body processes sugar. Similarly, 13C-lactate and 13C-glucose have been used in imaging studies without safety concerns.

For 13C-acetate, research suggests it does not affect important metabolic levels in tumors or nearby tissues, indicating safety in use.

Lastly, 13C-glutamine, a common amino acid involved in many body functions, has not shown any harmful effects in research.

In summary, these tracers are well-tolerated, and studies have not reported significant adverse events. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of metabolic tracers like 13C-Acetate, 13C-Fructose, 13C-Glucose, 13C-Glutamine, and 13C-Lactate for kidney cancer because these tracers provide a unique way to map cancer metabolism directly in the body. Unlike traditional imaging techniques, which often only show the size and location of tumors, metabolic tracers can reveal how tumors use nutrients, offering insights into their growth and behavior. This approach could lead to more personalized treatment plans by identifying specific metabolic vulnerabilities in a patient's cancer, potentially making treatments more effective. Additionally, it could help in early detection of treatment response, allowing for quicker adjustments to therapeutic strategies.

What evidence suggests that this trial's treatments could be effective for kidney cancer?

This trial will examine the effects of various metabolic tracers on kidney cancer. Participants will receive one of the following tracers: 13C-Fructose, 13C-Glucose, 13C-Lactate, 13C-Acetate, or 13C-Glutamine. Research has shown that certain nutrients can promote the growth of kidney cancer cells. Fructose can accelerate the growth and spread of these cells while reducing their death. Cancer cells use glucose for energy and growth, though its role may vary in kidney cancer. Lactate influences the tumor environment, aiding cancer cell survival. Acetate plays a role in cancer cell metabolism, and targeting it might slow cancer growth. Glutamine is vital for cancer cells, providing energy and aiding survival. Researchers aim to understand how these nutrients fuel cancer growth, potentially leading to new treatment options. ^{3 6 7 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

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]

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]

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 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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-leiomyomatosis-8-2019-cc189

Metabolic Tracers 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.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8773685/

Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate ... This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP- ...

3. researchgate.net researchgate.net/publication/392032047_Evaluating_the_metabolic_effects_of_neoadjuvant_treatment_in_clear_cell_renal_cell_carcinoma_using_hyperpolarised_1-13Cpyruvate_MRI

Evaluating the metabolic effects of neoadjuvant treatment ... This is the first study to evaluate the potential of clinical HP 13C-MRI in assessing early treatment response in renal cancer, which detected ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11669533/

ACSS1-dependent acetate utilization rewires mitochondrial ... Lastly, we observe decreased melanoma metastatic growth in the kidney and liver when ACSS1 expression is suppressed, demonstrating that ACSS1- ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2211124724013391

ACSS1-dependent acetate utilization rewires mitochondrial ... Our study highlights a key role for ACSS1-dependent acetate metabolism for cancer growth, raising the potential for ACSS1-targeting therapies in cancer.

6. digitalcommons.library.tmc.edu digitalcommons.library.tmc.edu/cgi/viewcontent.cgi?article=4105&context=uthgsbs_docs

Mitochondrial Complex I Promotes Kidney Cancer Metastasis The conditions that we used to infuse [1,2-13C]acetate did not alter acetyl-CoA levels in tumours or adjacent kidneys and produced similar ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/n/spr9781071609781/ch16/

Hyperpolarized Carbon (13C) MRI of the Kidneys - NCBI - NIH Here we introduce the general concept of HP 13C MRI and review the most relevant probes and applications to renal disease, including kidney ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9934542/

Mitochondrial metabolism in primary and metastatic human ... The conditions we used to infuse [1,2-13C]acetate did not alter acetyl-CoA levels in tumours or adjacent kidneys and produced similar levels of acetyl-CoA ...

9. biorxiv.org biorxiv.org/content/10.1101/2023.02.06.527285v1.full.pdf

Mitochondrial metabolism in primary and metastatic human ... kidney cancer. Labeling from [U-13C]glucose varies across cancer ... infusion of [1,2-13C]acetate at 1.5 mg/kg/minute. Patients ...