Objective : Transarterial chemoembolization (TACE) is the most common treatment for hepatocellular carcinoma (HCC) in the United States. TACE blocks HCC’s arterial blood supply, effecting locoregional restriction of oxygen and nutrient supply. While TACE slows disease progression, a majority of patients experience recurrence following a period of apparent latency after undergoing TACE. Current diagnostic imaging modalities are unable to identify latent cell populations predating recurrence, thus failing to identify patients who could benefit from repeat interventions. We hypothesized that magnetic resonance spectroscopy enhanced by dynamic nuclear polarization (DNP-MRS) may provide a functional readout of tumor metabolism that detects viable tumor cells following TAE when conventional imaging cannot.
Methods : Bland TAE was performed in male Wistar rats after appreciation of HCC tumor nodules greater than 5 mm in diameter following ad libitum intake of 0.01% diethylnitrosamine for 12 weeks. Study animals underwent conventional magnetic resonance (MR) imaging and spectroscopic imaging (following administration of [1-13C]-DNP-Pyruvate) before and after (post-operative days 4, 7, & 14) embolization. Images and spectra were analyzed and quantified with MATLAB. Animals that survived 14 days beyond embolization (n=6) were sacrificed and histologic examination of tumor tissue was performed.
Results : [1-13C]-DNP-Pyruvate demonstrated a statistically significant decrease in tumor perfusion following TAE (n=6; p<0.05). Interestingly, tumoral delivery of pyruvate persisted when viability was not evident on conventional imaging (n=18). Furthermore, lactate (n=18) and alanine (n=16) generation provided functional metabolic readouts of viability that were confirmed by histology. Recurrence on conventional imaging was appreciated in two of six animals within two weeks of embolization.
Conclusions : DNP-MRS provides a functional readout of tumor metabolism that has an increased sensitivity to detect cancer latency following TAE as compared to conventional MR imaging. This technology may help identify candidates for secondary interventions or adjuvant therapeutics.