Upper gastrointestinal (GI) cancers are a major health problem in Canada. At the metastatic stage, options are limited (usually chemotherapy, immunotherapy, personalized therapies under research protocols). These options are not applicable to all patients and may have significant toxicities. Endoradiotherapy (ERT) using a radioisotope coupled with a localization vector specifically targeting tumor cells to deliver a localized dose of radiation therapy is a promising avenue as it can treat disseminated neoplastic disease in a specific manner sparing healthy tissue with minimal side effects. The main goal of this study is to confirm that patients with upper GI cancer would be eligible for ERT (177Lu-PSMA treatment by using 68Ga-PSMA PET/CT assessment).

Background: Upper gastrointestinal (GI) cancers are a major health problem in Canada. At the metastatic stage, options are limited (usually chemotherapy, immunotherapy, personalized therapies under research protocols). These options are not applicable to all patients and may have significant toxicities. Endoradiotherapy (ERT) using a radioisotope coupled with a localization vector specifically targeting tumor cells to deliver a localized dose of radiation therapy is a promising avenue as it can treat disseminated neoplastic disease in a specific manner sparing healthy tissue with minimal side effects.

177Lu-PSMA would be a potentially usable ERT agent for upper GI cancers. Initially developed for prostate cancer, for which it has been successfully proven, it targets the PSMA protein found on tumor cells or their microenvironment. Its localization is usually confirmed by imaging with 68Ga-PSMA, which is the other component of its theranostic pair.

There are many case reports showing significant accumulation of 68Ga-PSMA in upper GI cancers, but there are no prospective studies to determine with certainty whether these are isolated cases or whether these tumors consistently uptake this agent; the same uptake that determines whether 177Lu-PSMA ERT has potential efficacy for these patients.

We believe that 177Lu-PSMA ERT could provide an effective radiation dose to treat metastatic high-grade GI cancers without exceeding acceptable dose limits to healthy tissue, providing a new therapeutic avenue for this patient group.

Objective:

1. To confirm that patients with upper gastric cancers would be eligible for 177Lu-PSMA treatment by using 68Ga-PSMA PET/CT assessment, according to the criteria suggested by the European Association of Nuclear Medicine (EANM) (tumor uptake 1.5 times higher than the liver)
2. Determine tumor heterogeneity (proportion of tumor lesions identified by computed tomography (CT) that capture 68Ga-PSMA) in each patient;
3. Determine the proportion of patients with lesions that do not accumulate 68Ga-PSMA;
4. Calculate the pharmacokinetics of 68Ga-PSMA by serial PET imaging;
5. Calculate dosimetry of healthy and tumor tissues;

Study population: Adults with upper metastatic gastric cancer (adenocarcinomas of the esophagus, stomach, bile ducts and pancreas)

Procedure and Follow-up: Patient will undergo 68Ga-PSMA PET imaging at different post-injection times (total visit duration of approximately half a day). Clinical data will be collected from this imaging and from the participant's medical record (demographic, treatment, medication, pathology, lab test results) for a 2-year follow-up period.

Inclusion Criteria:

• Age 18 years and older

• Active cancer of the type adenocarcinoma (of the esophagus, of the stomach, of the bile ducts, or of the pancreas) documented by a CT scan performed within the last 8 weeks at the time of recruitment.

  • An active cancer is defined as at least one lesion identified as stable or progressive neoplastic on CT imaging.
  • A lesion treated with local therapy (e.g., external radiotherapy, cryoablation, radiofrequency ablation, resection) is not counted for inclusion criteria if this is done between the CT scan and the 68Ga-PSMA PET imaging. A lesion treated prior to the last CT scan may be considered eligible if progression is documented at the last CT scan.

• Able to provide free and informed consent.

• Feasibility to perform 68Ga-PSMA PET within 2 months of the CT scan that was used for inclusion.

Exclusion Criteria:

• Other active cancer (non-metastatic non-melanoma skin cancer excluded). Cancer in remission for at least 3 years will not be considered active.
• ECOG > 3.
• Pregnant woman.
• Unable to follow study rules.