The goal of this clinical trial is to evaluate the clinical efficacy and safety of endoscopic ultrasonography (EUS)-guided radioactive iodine 125 seeds in combination with AG regimen chemotherapy for the treatment of metastatic pancreatic cancer. The main questions it aims to answer are:

• whether the combination of minimally invasive endoscopy-guided local radiation therapy with chemotherapy may improve overall survival
• the adverse events of the combination therapy Participants will receive the implantation of radioactive seeds under EUS guide. 48h after implantation, chemotherapy with Gem/nab-P given on days 1 and 8 of each 21-day cycle will be conducted.

Researchers will compare the I125+AG group with the group that takes AG chemotherapy alone to see if the overall survival can be improved.

Inclusion Criteria:

(Before the trial, subjects must meet all of the requirements listed below in order to be enrolled)

1. 18 to 80 years old;
2. Stage IV pancreatic ductal adenocarcinoma with distant metastases confirmed by clinical, imaging, and pathology, and the primary and metastatic mass can be measured on imaging.
3. No treatment history of chemotherapy, radiotherapy, or surgery
4. Expected survival > 6 months
5. ECGO score of 0-2
6. Eligible for chemotherapy (white blood cell > 3.5×109/L, neutrophil value > 1.5×109/L, hemoglobin > 80g/L, platelets > 100×109/L, albumin > 25g/L, alanine aminotransferase or aspartate aminotransferase ≤ 3 times the upper limit of normal and total bilirubin level ≤ 34.2umol/L, creatinine < 176.8 umol/L, normal ECG)
7. Signed written informed consent;

Exclusion Criteria:

1. Contraindication of EUS-guide procedure or technical infeasibility (e.g.,coagulation disorder, anatomical changes, large vessels along the puncture path)
2. Pregnant or breastfeeding
3. Presence of brain metastases
4. Presence of deep vein thrombosis or pulmonary embolism
5. Presence of HIV, HBV, HCV infection or other uncontrollable active infection
6. Hypersensitivity to chemotherapy drugs
7. History of other malignancies within 5 years
8. Peripheral neuropathy or interstitial lung disease within 5 years
9. Patient is enrolled in any other clinical protocol or investigational trial.

Patients will be randomly assigned(1:1) to the two treatment groups by an independent staff who is not involved in the treatment. The endoscopist and patient are not masked because they exactly know whether EUS-guided implantation is performed or not. Survival will be assessed by blinded researchers during follow-up.