About

Kavindra Nath, Ph.D., is a Research Associate Professor of Radiology at the University of Pennsylvania's Perelman School of Medicine. He is an associate member of the Institute of Translational Medicine and Therapeutics (ITMAT) and the Penn Medicine Abramson Cancer Center, where he serves as the Director of the Molecular Imaging Section in the Department of Radiology. His research expertise focuses on metabolic modulation to improve therapeutic responses in cancer, developing methods to selectively acidify and de-energize human cancers by exploiting their glucose-to-lactate conversion, which enhances tumor sensitivity to chemotherapy, radiation therapy, hyperthermia, and photodynamic therapy. Dr. Nath employs noninvasive magnetic resonance spectroscopy techniques to identify metabolic biomarkers that predict and monitor treatment responses, particularly in melanoma, lymphoma, and prostate cancer models. His work aims to advance personalized cancer treatment strategies through metabolic imaging and targeted metabolic interventions.

Research topics

• Medicine
• Chemistry
• Internal medicine
• Cancer research
• Nuclear magnetic resonance

Selected publications

• Metabolic Signatures of Dual mTOR Inhibition in Diffuse Large B-Cell Lymphoma

  Research Square · 2026-03-11

  preprintOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Prostate cancer: metabolic remodelling in expressed prostatic secretions reveals cellular structural changes measured by mpMRI

  Molecular Omics · 2026-03-01

  article

  Early and accurate differentiation of prostate cancer (PC) from benign prostatic hyperplasia (BPH) remains challenging; metabolomics enables biomarker discovery by capturing disease-specific metabolic changes. The study includes 64 expressed prostatic secretion from 31 PC cases and 33 BPH cases. Nuclear magnetic resonance spectroscopy was used for metabolomics. Multivariate analyses, including principal component analysis, orthogonal partial least squares discriminant analysis, and artificial neural network modelling, were performed to identify discriminative metabolites. Diagnostic performance was assessed using receiver operating characteristic curve analysis. Clinical correlations with prostate-specific antigen (PSA) levels, multiparametric MRI (mpMRI), and Gleason score (GS) were executed. Citrate, glutamate, myo-inositol, and cis-aconitate were identified as key metabolites distinguishing PC from BPH, showing significant correlations with PSA, mpMRI-derived Prostate Imaging Reporting and Data System scores and apparent diffusion coefficient values as well as histopathology-based GS. The identified metabolic signature demonstrates strong potential as a noninvasive tool to support early PC detection and clinical decision-making, showing correlation with PSA, mpMRI indices and GS to enhance diagnostic accuracy before structural changes become evident.

  PublisherDOI

• Metabolic and Functional Imaging Biomarkers of Response to Immunotherapy in Melanoma

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  articleSenior author

  Motivation: Studying immunotherapy effects at the subcellular level in melanoma may reveal critical biomarkers of response and improve therapeutic strategies. Goal(s): We aim to study the impact of anti-PD-1 immunotherapy on metabolite levels, bioenergetics, pH, diffusivity, and T2 relaxation times in immunogenic melanoma models. Approach: We used in vivo MRI and MRS to assess the impact of anti-PD-1 immunotherapy on the immunogenic melanoma model YUMMER1.7. Results: Early-phase changes in lactate, alanine, pH, bioenergetics, ADC, and T2 relaxation time occurred during anti-PD-1 immunotherapy. Preliminary in vitro studies with two metabolic modulators further characterized the metabolic phenotypes of isolated YUMMER1.7 melanoma cells. Impact: This study emphasizes the potential of early subcellular changes (metabolism, pH, bioenergetics, diffusion, T2 relaxation) as predictive biomarkers of melanoma immunotherapy response. Preliminary findings with metabolic modulators indicate possible strategies for enhancing treatment outcomes through metabolic modulation.

  PublisherDOI

• Magnetic resonance spectroscopy–based detection of response to therapy targeting glutaminolysis in lymphoma

  Blood Neoplasia · 2025-04-15

  articleOpen access1st authorCorresponding
  PublisherDOI

• Metabolic inhibition therapy targeting glutaminolysis in mantle cell lymphoma

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  article1st authorCorresponding

  Motivation: Mantle cell lymphoma (MCL) poses clinical challenges due to resistance to current treatment modalities. Targeting cell metabolism may prove new therapeutic approach to MCL. Goal(s): We evaluated effectiveness of CB-839, a glutaminase inhibitor, against MCL in in vitro and in vivo preclinical studies. Approach: We employed 1H magnetic resonance spectroscopy (1H MRS) imaging and biochemical analyses to investigate the effects of CB-839 on key metabolites in MCL cells, to potentially identify biomarkers of treatment response. Results: Decreases in lactate and alanine concentration emerged as promising biomarkers of response to CB-839 and may potentially serve as biomarkers in MCL patients. Impact: Therapy-mediated decreased intra-tumoral concentrations of lactate and alanine measured by 1H MRS may potentially become early and sensitive biomarkers of glutaminase inhibition in MCL and, likely, other types of malignancies.

  PublisherDOI

• Enhancing Radiation Therapy Response in Prostate Cancer Through Metabolic Modulation by Mito-Lonidamine: A 1H and 31P Magnetic Resonance Spectroscopy Study

  International Journal of Molecular Sciences · 2025-01-09

  articleOpen accessSenior authorCorresponding

  Radiation therapy (RT) is the cornerstone treatment for prostate cancer; however, it frequently induces gastrointestinal and genitourinary toxicities that substantially diminish the patients’ quality of life. While many individuals experience transient side effects, a subset endures persistent, long-term complications. A promising strategy to mitigate these toxicities involves enhancing tumor radiosensitivity, potentially allowing for lower radiation doses. In this context, mito-lonidamine (Mito-LND), an antineoplastic agent targeting the mitochondrial electron transport chain’s complexes I and II, emerges as a potential radiosensitizer. This study investigated Mito-LND’s capacity to augment RT efficacy and reduce adverse effects through comprehensive in vitro and in vivo assessments using hormone-sensitive and hormone-refractory prostate cancer models. Employing a Seahorse analysis and 1H/31P magnetic resonance spectroscopy (MRS), we observed that Mito-LND selectively suppressed lactate production, decreased intracellular pH, and reduced bioenergetics and oxygen consumption levels within tumor cells. These findings suggest that Mito-LND remodels the tumor microenvironment by inducing acidification, metabolic de-energization, and enhanced oxygenation, thereby sensitizing tumors to RT. Our results underscore the potential of Mito-LND as a therapeutic adjunct in RT to improve patient outcomes and reduce radiation-associated toxicities in early-stage prostate cancer.

  PublisherOA PDFDOI

• MRS and Optical Imaging Studies of Therapeutic Response to Combination Therapy Targeting BRAF/MEK in Murine Melanomas

  Academic Radiology · 2025-02-20 · 1 citations

  articleOpen accessSenior author

  <h3>Rationale and Objectives</h3> Melanoma, an aggressive skin cancer, often harbors BRAFV600E mutations driving tumor progression via the mitogen-activated protein kinase (MAPK) pathway. While targeted therapies like BRAF (dabrafenib) and MEK (trametinib) inhibitors have improved outcomes, resistance linked to metabolic reprogramming remains a challenge. This study investigates metabolic changes induced by dual BRAF/MEK inhibition in a BRAFV600E-mutant murine melanoma model using magnetic resonance spectroscopy (MRS), optical redox imaging (ORI), and biochemical assays. We aim to identify metabolic biomarkers for predicting therapeutic response or resistance. <h3>Materials and Methods</h3> YUMM1.7 murine melanoma cells and tumored mice were treated with dabrafenib and trametinib. ORI assessed mitochondrial redox status by measuring reduced nicotinamide adenine dinucleotide (NADH), oxidized flavoproteins (Fp), and the redox ratio (Fp/(NADH+Fp)) in vitro. Glucose consumption and lactate production were analyzed using a YSI Biochemical Analyzer. In vivo metabolic changes were monitored via ¹H and ³¹P MRS, evaluating lactate, alanine, pH, βNTP/Pi, and total NAD(P)(H), which represents combined oxidized nicotinamide adenine dinucleotide (NAD⁺), NADH, and reduced nicotinamide adenine dinucleotide phosphate (NADPH). <h3>Results</h3> Under the combined therapeutic regimen of dabrafenib and trametinib, YUMM1.7 murine melanoma cells exhibited significant inhibition of lactate generation, non-significant reduction of glucose utilization, decreased intracellular levels of NADH and total NAD(P)(H), and more oxidized redox status in vitro, which can be interpreted as inhibition of the Warburg effect and improved OXPHOS efficiency by targeting BRAF/MEK signaling activities. Furthermore, YUMM1.7 mouse tumors demonstrated less tissue acidification and improved bioenergetics (βNTP/Pi), in agreement with the in vitro data. <h3>Conclusion</h3> MRS, ORI, and biochemical assays identified critical metabolic changes, highlighting potential biomarkers and supporting the integration of metabolic inhibitors with MAPK-targeted therapies to improve clinical outcomes.

  PublisherOA PDFDOI

• Metabolic Biomarkers of Therapeutic Response in YUMM1.7 Melanoma Targeting BRAF and MEK Inhibition

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  articleSenior author

  Motivation: Monitor the metabolic effects of a combined dabrafenib and trametinib therapy in YUMM1.7 melanoma models using 1H/31P MRS. Goal(s): Test the metabolic effects of the combined BRAF and MEK inhibition in YUMM1.7 melanoma models. Approach: We use in vivo, 1H/31P MRS, tests to measure lactate, alanine, bioenergetics (β-NTP/Pi), and NAD(H). We aim to test whether they are early, sensitive biomarkers for the combined therapy response in the YUMM1.7 melanoma model. Results: Rapid changes in lactate, alanine, bioenergetics, and NADH in response to combined dabrafenib and trametinib therapy are closely linked to subsequent tumor response. Impact: This study shows that combining dabrafenib and trametinib may block the overactive BRAF and MEK proteins. Variations in critical metabolites (lactate and alanine), bioenergetics, NADH, and pH may explain differential therapeutic responses in YUMM1.7 melanoma models.

  PublisherDOI

• 1H and 31P Magnetic Resonance Spectroscopic Metabolomic Imaging: Assessing Mitogen-Activated Protein Kinase Inhibition in Melanoma

  Cells · 2024-07-19 · 3 citations

  articleOpen accessSenior authorCorresponding

  The MAPK signaling pathway with BRAF mutations has been shown to drive the pathogenesis of 40–60% of melanomas. Inhibitors of this pathway’s BRAF and MEK components are currently used to treat these malignancies. However, responses to these treatments are not always successful. Therefore, identifying noninvasive biomarkers to predict treatment responses is essential for personalized medicine in melanoma. Using noninvasive 1H magnetic resonance spectroscopy (1H MRS), we previously showed that BRAF inhibition reduces lactate and alanine tumor levels in the early stages of effective therapy and could be considered as metabolic imaging biomarkers for drug response. The present work demonstrates that these metabolic changes observed by 1H MRS and those assessed by 31P MRS are also found in preclinical human melanoma models treated with MEK inhibitors. Apart from 1H and 31P MRS, additional supporting in vitro biochemical analyses are described. Our results indicate significant early metabolic correlations with response levels to MEK inhibition in the melanoma models and are consistent with our previous study of BRAF inhibition. Given these results, our study supports the potential clinical utility of noninvasive MRS to objectively image metabolic biomarkers for the early prediction of melanoma’s response to MEK inhibition.

  PublisherOA PDFDOI

• In Vivo Measurement of Regional Brain Nicotinamide Adenine Dinucleotide (NAD) by 31P MR Spectroscopic Imaging at 1.5 T

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2024-11-26

  article

  Motivation: Our incentive is to validate the clinical translation of the nicotinamide adenine dinucleotide (NAD) indices as biomarkers in aging and neurodegenerative diseases in clinically accessible 1.5T MR scanners. Goal(s): We aimed to demonstrate the feasibility of the noninvasive assessment of the NAD indices in the human brain using 31P magnetic resonance spectroscopic imaging at 1.5 T. Approach: We used advanced data processing, including principal component analysis, and performed simulations to support quantifying the brain NAD indices using low magnetic fields. Results: Our results demonstrate that total NAD is reliably measured under our conditions, making it a potential metabolic biomarker for aging and neurodegeneration. Impact: Brain nicotinamide adenine dinucleotide is a potential biomarker and therapeutic target in aging and neurodegeneration. Its noninvasive measurement by 31P magnetic resonance spectroscopic imaging on highly accessible 1.5T clinical scanners will facilitate its biomarker development and treatment utility.

  PublisherDOI

Recent grants

• Metabolic Biomarkers of Response of Mantle Cell Lymphoma to Bruton Tyrosine Kinase Inhibition

  NIH · $2.5M · 2020–2026

• Metabolic Imaging of Targeted Therapies in Cancer

  NIH · $3.0M · 2022–2026

• Melanoma: Metabolic Biomarkers of Response to Targeted Therapy

  NIH · $2.4M · 2020–2026

Frequent coauthors

• Rakesh K. Gupta

  Fortis Memorial Research Institute

  47 shared

• M. Albert Thomas

  University of California, Los Angeles

  38 shared

• Ramkishore Singh Rathore

  36 shared

• Pranav Kumar Mandal

  36 shared

• Jitesh Singh

  GLA University

  36 shared

• Sona Saksena

  Thomas Jefferson University

  36 shared

• David Nelson

  University of Pennsylvania

  24 shared

• Jerry D. Glickson

  University of Pennsylvania

  24 shared

Labs

• Laboratory of Molecular ImagingPI

Education

• Research Assistant Professor, Radiology

  University of Pennsylvania