Next Generation Precision Imaging for Cancer Immunotherapy: Dynamic Nuclear Polarization and Metabolomics Study

The investigators plan a 3-year trial with a randomized, two-groups allocation observational study design that will enroll 90 subjects with newly diagnosed or recurrent gynecological cancer from Linkou Chang Gung Memorial Hospital (CGMH) receiving ICI therapy for this prospective study. Standard cares, eg. MRI/CT/PET, are priorly required for the first-line screening method, with tumor slides and routine blood work at the initial visit. After being randomly assigned, 30 eligible subjects will be assigned to the next-generation imaging group, and will receive two integrated examinations between the baseline and 2 weeks of immunotherapy-the integrated examination of DNP and metabolomics.

Subjects in the next-generation imaging group will receive splenic DNP imaging, followed by non-contrast-enhancing MRF at the lesion and MR Relaxometry, which provide quantitative measurements of metabolism occurring within the spleen and within the cancer cells, respectively. DNP is injected with 13C contrast agent hyperpolarized 13C pyruvate (HP [1-13C] Pyruvate) intravenously in the arm, and the study drug is injected at a dose of 0.43 ml/kg, which is labeled with the non-radioactive isotope 13C at the C1 position, hyperpolarized 13C signals are obtained through MR spectrum acquisition, and then MRF sequences are performed to obtain multi-parameter tissue characteristics. The general imaging group will receive the same MR strategies but without spleen DNP scan.

All MRI sequences will be performed on a 3T clinical scanner (Discovery MR750w,GE Healthcare, Milwaukee, USA) with a flexible surface 13C/1H multinuclear transmit-receive coil (RAPID Biomedical, Bavaria, Germany) to cover the splenic region.

DNP-MRI:

To comply with the Good Manufacturing Practice (GMP) of pharmaceuticals, [1-13C]pyruvate for human will be prepared in the ISO 8 clean room and ISO 5 laminar flow in the Department of Nuclear Medicine, Chang Gung Memorial Hospital at Linkou, Taiwan. The premixed [1-13C]pyruvic acid/12.5 mM Electronic Paramagnetic Agent (Electronic Paramagnetic Agent; EPA; AH111501, GE Healthcare, Oslo, Norway) will be packed into a sterile pharmacy Kit (Sterile Fluid Path; SFP, GE Research Circle Technology) and polarized in the polarizer (SPINlab, GE Research Circle Technology) at 0.7 - 0.8 K and a magnetic field of 5 T for at least 2 - 3 hrs. After being quickly dissolved in heated water, it will pass through an EPA filter to remove excess EPA and be mixed with neutralization medium (NaOH/TRIS/EDTA) in the receiver, and then automatically detected by optical measurement in the QC machine (GE GE Research Circle Technology), including pyruvate concentration, EPA concentration, pH, temperature, volume, and polarization level, while simultaneously drawing a solution containing hyperpolarized [1-13C]pyruvate through a 0.2 μm terminal filter (ZenPure, Manassas, Virginia) into an administration syringe (Medrad, Warrendale, Pennsylvania) to ensure sterility. After the responsible physician checks that the QC parameters meet the criteria, the patient will be injected intravenously at a dose of 0.43 mL/Kg at a flow rate of 5 mL/s, and then flushed with 20 mL of physiological saline. Terminal filter integrity (Threshold = 50 psi) will be checked immediately after dispensing.