This clinical trial is a single-center, open-label, non-randomized first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics, radiation dosimetry, and preliminary efficacy of SNA028 (which is a two-step radioactivity pretargeting agents conducted by GPA33-CC and 177Lu-SmartD2) in patients with GPA33-positive colorectal cancer who have experienced disease progression/recurrence following prior standard therapy.

The trial is planned to explore three main topics: 1.the dose of GPA33-CC. 2. the intervation between administration of GPA33-CC Inervation and 177Lu-SmartD2. 3.the mass dose of SmartD2.

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 colorectal cancer diagnosed by histopathology or cytology and experiencing imaging progression/recurrence after standard treatment;
6. According to RECIST 1.1 definition, there must be at least one measurable lesion;
7. Toxicity caused by previous treatment must be restored to ≤ level 2 (CTCAE v6.0) or to a stable state evaluated by the researcher (excluding hair loss and pigmentation);
8. Having sufficient organ function, defined as follows:

1) Bone marrow:

• White blood cell count 3.0~10.0 × 10^9/L
• Absolute neutrophil count 1.5~7.0 × 10^9/L
• Platelets 75~300 × 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 9. 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. Poor nutritional status and inability to tolerate the test subjects;
2. Individuals who have previously been allergic to SNA028 components or their analogues;
3. Patients who have received therapeutic drugs and radiation therapy labeled with 177Lu and other radioactive isotopes 4 weeks before SNA028 treatment;
4. Patients who have received other experimental anti-tumor drug treatments 4 weeks before SNA028 treatment;
5. Patients who received anti-GPA33 antibody treatment 4 weeks before SNA028 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. Diagnosed with other malignant tumors that may alter life expectancy or interfere with disease assessment;
9. Pregnant or lactating women;
10. The researcher believes that they are not suitable to participate in this clinical study.