Hyperpolarized 13C Pyruvate MRI for Early Immune Evaluation in Cervical Cancer Patients At Baseline and CCRT Therapy

Precision Medicine Imaging for Cervical Cancer: Integrating MR Fingerprinting, Dynamic Nuclear Polarization (DNP)-MRI and Artificial Intelligence Radiomics

In this single armed, single-center, case-controlled study, the investigators will conduct a prospective trial and integrate the most advanced imaging technology to medical practice, attempting to solve the problem detected by radiomics approach. The investigators plan a 3-year project with non-randomized, single group assignment observational study design. Thirty participants with diagnosed LACC that are to receive CCRT are to be recruited for this prospective single institutional study from Chang Gung Memorial Hospital at Linkou (CGMH). Standard-of-care MRI/CT that is required for staging will be the first line screening method. A tumor biopsy and routine blood test will be obtained at the time of the initial clinic visit. Participants eligible for this study will receive two investigative exams-MRF, CEST, DNP-MRI MRI and Metabolomics, at baseline and the 2-week during CCRT.

The new imaging methods being tested are MRF and CEST without contrast enhancement, and DNP-MRI which provides quantitative measurement of the metabolism occurring within cancer cells. It also involves injection of a contrast agent-Hyperpolarized pyruvate (13C) Injection. The participants will be injected with the study drug at a dose of 0.43 ml/kg and then receive MRI scan.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: Hyperpolarized 13C Pyruvate

Detailed Description

Primary objective

1. Bridging the Gap between Imaging and Biology. DNP is the only technology that can measure real-time flux of pyruvate to lactate conversion and mitochondria metabolism. DNP-MRI will combine the strength of MRI (anatomy, tissue contrast via MRF, CEST and DWI) and DNP (biochemistry measurement), and the blood/urine metabolomics approach, to noninvasively bring more insightful information for clinical application.
2. Precision Medicine for Precision Response Prediction. Although AI or deep learning can identify high-risk patient for particularly treatment (CCRT in this project), the predictive model is based on prior database rather than this particular patient. The investigators urgently need a non-invasive precise measurement to monitor the response in a real-world situation, to reduce the treatment uncertainty, to select the most cost-effective treatment. This is of paramount importance for the more advanced treatment i.e. target therapy, immunotherapy etc. The investigators did not intend to change the standard-of-care but the information provided by this study will help to investigate the fundamental mechanisms hence providing hopes for alternative treatments.
3. Infrastructures for MR Fingerprinting and Dynamic Nuclear Polarization (DNP)-MRI Research for Taiwanese researchers. The investigators are very grateful to be able to install the first DNP system dedicated to human research in Asia and would like to introduce this novel technology to Taiwan. Currently, human DNP study has only been conducted in the USA (UCSF, MD Anderson Cancer Center and Memorial Sloan-Kettering Cancer Center) and the UK (University College of London, Oxford and Cambridge) and Canada (Toronto University). Based on our preliminary efforts of tracer preparation, multi-nuclei scanning equipment and dedicated pulse sequences, the investigators aim to build infrastructures for MR Fingerprinting and DNP-MRI Research for Taiwanese research groups.

Secondary objective

1. Translate technical advancements to clinically applicable tools
2. Converge integrated information to construct the prediction model
3. Establish the delta radiomics prediction model with biological meaningfulness

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Guishan District
    • Taoyuan City, Guishan District, Taiwan, 333
      • Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed carcinoma of the uterine cervix.
2. Age ≥ 20 years.
3. Clinical International Federation of Gynecology and Obstetrics (FIGO) stage IB2-IV.
4. Tumor diameter ≥ 4 cm, verified by MRI or CT.
5. Scheduled curative-intent non-surgical treatment.

Exclusion Criteria:

1. Contraindication to MRI study (e.g. claustrophobia, cardiac pacemaker, metal implants in pelvis).
2. Inadequate marrow, liver and renal functions.
3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
4. Pregnant or breast-feeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hyperpolarized 13C pyruvate DNP-MRI scan; Patients receive hyperpolarized 13C pyruvate through IV injection less than 1-2 minute then undergo MRI over 3-5 minutes at baseline and 2 weeks after CCRT treatment. Total 2 times of MRI scan.	Drug: Hyperpolarized 13C Pyruvate; Procedure: Magnetic Resonance Imaging Undergo 1H-MRI of DWI/MRF/CEST for tumor cite following by 13C DNP-MRI for spleen for 3-5 minutes after hyperpolarized 13C pyruvate injection; Other Names: Hyperpolarized Pyruvate (13C); Hyperpolarized Carbon C 13 Pyruvate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI size measurement of the primary tumor	Tumor size measurement by regular MRI	Change from baseline in tumor size at 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent rate	Follow-up recurrent rate	Follow-up for 5 years

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Collaborators: Ministry of Science and Technology, Taiwan
• Investigators: Principal Investigator: Gigin Lin, MD, PhD, Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2021
• Primary Completion (Actual): July 31, 2024
• Study Completion (Actual): July 31, 2024

Study Registration Dates

• First Submitted: June 21, 2021
• First Submitted That Met QC Criteria: June 28, 2021
• First Posted (Actual): July 7, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Precision medicine; Artificial intelligence; Cervical cancer; Radiomics; Magnetic resonance fingerprinting; Hyperpolarized 13C pyruvate; Dynamic nuclear polarization
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Uterine Cervical Neoplasms
• Other Study ID Numbers: 201702080A0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes