This clinical trial is a single-center, open-label, non-randomized, first-in-human (FIH), dose-escalation study evaluating the safety, tolerability, and preliminary efficacy of 177Lu-DOTA-SNA040 in patients with advanced Claudin18.2-positive solid tumors (e.g., gastric cancer, gastroesophageal junction adenocarcinoma, pancreatic cancer, cholangiocarcinoma, etc.) who have disease progression following first-line therapy.

Eligible subjects should first undergo 68Ga-NODAGA-SNA014 PET/CT imaging. Patients with negative 68Ga-NODAGA-SNA014 tumor uptake will be discharged from the study after one week of follow-up for adverse events. Patients with positive 68Ga-NODAGA-SNA014 tumor uptake (SUVmax ≥10) will proceed to the subsequent 177Lu-DOTA-SNA040 dose escalation study (with at least a 2-day interval between 68Ga-NODAGA-SNA014 imaging and 177Lu-DOTA-SNA040 treatment). After completing the first cycle of dosing for DLT observation, subsequent 2-6 cycles of 177Lu-DOTA-SNA040 treatment may be administered. For dose group 1, the subsequent 2-6 cycles of 177Lu-DOTA-SNA040 dosing activity will be determined by the investigator, with the dose per cycle adjustable. For dose groups 2-4, the 177Lu-DOTA-SNA040 dosing activity will follow the fixed original dose (e.g., the first cycle dose for dose group 2 is 100 mCi, with subsequent 2-6 cycles fixed at 100 mCi).

Inclusion Criteria:

1. Age range of 18 to 75 years old (including boundary values);
2. Individuals with behavioral capacity who voluntarily participate in this clinical study and sign an informed consent form (ICF);
3. Individuals with ECOG scores ranging from 0 to 1 (see Appendix 1 for details);
4. Life expectancy>6 months;
5. Patients with advanced solid tumors confirmed by histopathology or cytology (such as gastric cancer or adenocarcinoma at the gastroesophageal junction, pancreatic cancer, and cholangiocarcinoma) and confirmed by the investigator, who fail to receive first-line treatment or have disease progression; According to RECIST 1.1 definition, there must be at least one measurable lesion;

7. At least one lesion must be immunohistochemistry positive for Claudin18.2 (≥ 20% of tumor cells have Claudin18.2 immunohistochemistry membrane staining intensity ≥ 2+); Before the first administration of 177Lu-DOTA-SNA040 treatment, the toxicity caused by previous treatments must be restored to ≤ level 2 (CTCAE V5.0) or a stable state evaluated by the researcher (excluding hair loss and pigmentation); 177Lu DOTA-SNA040 has sufficient organ function one week before treatment, defined as follows:

1. Bone marrow:

   White blood cell count range from 3.0 to 10.0 × 10^9/L Absolute neutrophil count range from 1.5 to 7.0 × 10^9/L Platelets range from 75 to 300 × 10^9/L Hemoglobin ≥ 90g/L

2. Liver:

   Total bilirubin ≤ 2.5 x upper limit of normal (ULN) Serum albumin>3.0 g/dL Alanine aminotransferase and aspartate aminotransferase ≤ 3 × ULN or liver metastasis patients ≤ 5 × ULN

3. Kidney:

   Serum/plasma creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 mL/min (calculated using the Cockcroft Gault formula)

4. Coagulation function The international standardized ratio of prothrombin is less than 1.5 × ULN Prothrombin time<2 × ULN During the treatment with 177Lu-DOTA-SNA040, the best support/standard of care agreed upon by the researcher is allowed; 11. Patients and/or partners with fertility must use adequate contraceptive measures during the study period and within 6 months after the last administration of the study drug.

Exclusion Criteria:

1. The nutritional status is extremely poor, with a BMI of less than 18.5 during screening, and the subjects cannot tolerate the test;
2. Individuals who have previously been allergic to 177Lu DOTA-SNA040 or its analogues;
3. Patients who have received therapeutic drugs and radiation therapy labeled with 177Lu and other radioactive isotopes 4 weeks before treatment with 177Lu DOTA-SNA040;
4. 177Lu DOTA-SNA040 patients who received antibody conjugated drug (ADC) treatment 4 weeks before treatment;
5. Those who have received other experimental anti-tumor drug treatments 4 weeks before 177Lu DOTA-SNA040 treatment;
6. Individuals known to have central nervous system metastases and/or malignant meningitis;
7. Major comorbidities: including but not limited to New York Heart Association grade III or IV congestive heart failure, a history of congenital QT interval prolongation syndrome, active severe infections, or other major diseases that the researcher deems unsuitable for participation in the study;
8. Patients with obvious gastric bleeding and/or untreated gastric ulcers;
9. Diagnosed with other malignant tumors that may alter life expectancy or interfere with disease assessment;
10. Pregnant or lactating women;
11. The researcher believes that they are not suitable to participate in this clinical study.