Hyperpolarized [1-¹³C]-pyruvate MRS evaluates immune potential and predicts response to radiotherapy in cervical cancer

BACKGROUND: Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1- 13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer.

METHODS: This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39-60) evaluated using HP [1- 13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton ( 1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups.

RESULTS: The splenic HP [1- 13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1- 13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1- 13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different.

CONCLUSIONS: This exploratory study revealed the feasibility of HP [1- 13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04951921 , registered 7 July 2021.

RELEVANCE STATEMENT: This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients' immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer.

KEY POINTS: • Effective radiotherapy induces abscopal effect via altering immune metabolism. • Hyperpolarized 13C MRS evaluates patients' immune potential non-invasively. • Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy.