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Hyperpolarized Metabolic Imaging Detects Latent Hepatocellular Carcinoma Domains Surviving Locoregional Therapy
- Source :
- Hepatology
- Publication Year :
- 2020
-
Abstract
- Background and aims Advances in cancer treatment have improved survival; however, local recurrence and metastatic disease-the principal causes of cancer mortality-have limited the ability to achieve durable remissions. Local recurrences arise from latent tumor cells that survive therapy and are often not detectable by conventional clinical imaging techniques. Local recurrence after transarterial embolization (TAE) of hepatocellular carcinoma (HCC) provides a compelling clinical correlate of this phenomenon. In response to TAE-induced ischemia, HCC cells adapt their growth program to effect a latent phenotype that precedes local recurrence. Approach and results In this study, we characterized and leveraged the metabolic reprogramming demonstrated by latent HCC cells in response to TAE-induced ischemia to enable their detection in vivo using dynamic nuclear polarization (DNP) magnetic resonance spectroscopic imaging (MRSI) of 13 carbon-labeled substrates. Under TAE-induced ischemia, latent HCC cells demonstrated reduced metabolism and developed a dependence on glycolytic flux to lactate. Despite the hypometabolic state of these cells, DNP-MRSI of 1-13 C-pyruvate and its downstream metabolites, 1-13 C-lactate and 1-13 C-alanine, predicted histological viability. Conclusions These studies provide a paradigm for imaging latent, treatment-refractory cancer cells, suggesting that DNP-MRSI provides a technology for this application.
- Subjects :
- 0301 basic medicine
Male
Carcinoma, Hepatocellular
Magnetic Resonance Spectroscopy
Ischemia
Article
Causes of cancer
03 medical and health sciences
0302 clinical medicine
Text mining
In vivo
medicine
Animals
Humans
Rats, Wistar
Hepatology
business.industry
Liver Neoplasms
Magnetic resonance spectroscopic imaging
medicine.disease
Phenotype
Embolization, Therapeutic
Magnetic Resonance Imaging
Rats
Disease Models, Animal
030104 developmental biology
Hepatocellular carcinoma
Cancer cell
Cancer research
030211 gastroenterology & hepatology
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Hepatology
- Accession number :
- edsair.doi.dedup.....85eb0af247df22af88a390b38e4e94f8