Precision medicine is a major goal in oncology. It aims to tailor treatments to the specific characteristics of each patient's tumor. This approach makes it possible to identify unique therapeutic targets and select the therapeutic alternative that specifically targets the abnormalities identified. Positron emission tomography (PET) plays a key role in this approach by providing detailed functional imaging of tumors in a non-invasive way. Usually, one radio-tracer is used to perform PET. Depending on the type of tumor, each tracer is carefully selected for its specific behavior and characteristics. However, it may be useful to perform several PET scans with different tracers, each providing different information, for the initial staging and therapeutic management of patients. Hepatocellular carcinoma (HCC), the most common form of liver cancer and the third leading cause of cancer-related death, requires precise imaging for optimal treatment selection. [18F]F-choline PET is often preferred for the initial detection of well-differentiated HCC and local recurrence, while [18F]FDG (fluorodésoxyglucose) PET is more useful for aggressive forms of HCC and for assessing metastases. Similarly, gastro-entero-pancreatic tumors (GEP-NETs), a type of neuroendocrine tumor found in the gastrointestinal tract and pancreas, also benefit from tailored imaging approaches. GEP-NETs commonly express somatostatin receptors, which are effectively targeted by [68Ga]Ga-DOTATOC PET to enhance diagnostic accuracy and staging, particularly in well-differentiated lesions. Conversely, [18F]FDG PET is valuable for imaging GEP-NETs with high metabolic activity, providing insight into tumor aggressiveness and proliferation. The combined use of [18F]FDG PET and [18F]F-choline PET in HCC, as well as [68Ga]Ga-DOTATOC PET and [18F]FDG PET in GEP-NETs, provides complementary information that helps to comprehensively characterize the tumor, guide treatment decisions, and monitor therapeutic response.

In this context, a highly innovative way using multiplexed PET imaging offers potential for targeted therapy and precision medicine. The aim of this study is to evaluate the use of simultaneous dual-tracer PET imaging with a staggered injection (referred to here as multiplexed PET), combining [18F]FDG and [18F]F-choline in HCC, and [68Ga]Ga-DOTATOC and [18F]FDG in GEP-NETs as compared to both pairs of single PET.

Inclusion Criteria:

• - Men or women ≥ 18 years

• Written informed consent

• Affiliation with French social security system or beneficiary from such system

• ECOG (Eastern Cooperative Oncology Group) performance ≤ 2

• Presence of at least one morphological evaluable lesion according to RECIST 1.1 using contrast CT (computer tomography)/MRI (Magnetic Resonance Imaging) (must be performed within 6 months before inclusion)

• Willing and able to follow scheduled visits and study procedure

• Cohort 1 and 3: Child-Pugh A for cirrhotic patients (initial diagnosis, suspected relapse or progression) with histologically proven diagnosis. Albumin > 28 g/L, total bilirubin < 35 µM/L, TP>50%. The biopsy may have been performed at any point, without time limitations before inclusion.

• Cohort 2: GEP-NET (initial diagnosis, suspected relapse or progression) with histologically proven with liver metastases and/or pancreatic involvement. The biopsy may have been performed at any point, without time limitations before inclusion.

• Women must meet one of the following criteria at the time of inclusion:

  • present a negative pregnancy test (blood test) before receiving the first dose of test drug and use highly1 effective contraceptive measures for a duration of 6 months after the multiplexed PET Scan
  • or be post-menopausal (aged over 50 with amenorrhea for at least 12 months after stopping all exogenous hormone treatments);
  • or (if under 50 years of age) have been in amenorrhea for at least 12 months after stopping exogenous hormone treatments and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels corresponding to post-menopausal levels;
  • or have undergone irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy (this operation must be documented);

• Male patients will be required to use male contraception (condoms) for a duration of 3 months after the multiplexed PET Scan ;

• Women partners will be required to use an acceptable2 contraceptive measure (as they will not receive the trial drug) for a duration of 3 months after the multiplexed PET Scan ;

• Male partners will be required to use male contraception (condoms) for a duration of 6 months after the multiplexed PET Scan.

Exclusion Criteria:

• - Known hypersensitivity to gallium-68, fluor-18 to any excipient or derivative or to radiographic contrast agents.
• Any major surgery within 4 weeks before enrollment.
• Any uncontrolled significant medical, psychiatric or surgical condition or laboratory findings that, in the opinion of the investigator, might jeopardise the subject's safety or that would limit compliance with the objectives and assessments of the study.
• Other known malignancies (except for fully-resected non-melanoma skin cancer or cervical cancer in situ) unless definitively treated and proven no evidence of recurrence for 2 years.
• Women who are pregnant or breastfeeding. A serum pregnancy test will be performed at the start of the study and within 48 hours prior to multiplexed PET scan for all female subjects of childbearing potential.
• Patient under guardianship or trusteeship.
• Patient under judicial protection.
• Patient unable to understand spoken or written French