Molecularly Targeted Radionuclide Therapy Via the Integrin Alphavbeta6

Inclusion Criteria:

\[68Ga\]Ga DOTA-5G PET/CT Inclusion Criteria:

1. Ability to understand and willingness to sign a written informed consent document.
2. Age 18 or more years
3. Pathologically confirmed NSCLC with metastatic disease and measurable disease per RECIST (version 1.1) (i.e. at least 1 lesion \> 1 cm or lymph node \> 1.5 cm in short axis)
4. Participant must have documented tumor progression for metastatic disease during or following at least one prior FDA approved systemic regimen as established by diagnostic imaging.
5. Available archival tumor tissue (excisional, core, or FNA is acceptable). Tissue from a metastatic site is preferred when available.
6. Eastern Cooperative Oncology Group Performance Status ≤ 2
7. Participant must have completed prior systemic therapy at least 2 weeks (washout period) prior to \[68Ga\]Ga DOTA-5G PET scan. Any clinically significant toxicity (with the exceptions of hair loss and sensory neuropathy) related to prior therapy resolved to Grade 1 or baseline.
8. Hematologic parameters defined as:

   Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 Platelet count ≥ 100,000/mm3 Hemoglobin ≥ 8 g/dL
9. Blood chemistry levels defined as:

   AST, ALT, alkaline phosphatase ≤ 5 times upper limit of normal (ULN) Total bilirubin ≤ 2 times ULN Creatinine ≤ 2 times ULN
10. Anticipated life expectancy ≥ 3 months
11. Able to remain motionless for up to 30-60 minutes per scan

\[177Lu\]Lu DOTA-ABM-5G therapy Inclusion Criteria:

1. Completion of entry into \[68Ga\]Ga DOTA-5G PET study and completion of scan
2. The presence of at least one measurable disease by \[68Ga\]Ga DOTA-5G PET/CT (SUVmax\>2-fold above normal bone, brain, lung or liver and identified on standard of care diagnostic imaging) Patients with a history of brain metastases and or any clinical concern for brain metastases will be evaluated with brain MRI as per standard of care for patients with metastatic NSCLC.

Exclusion Criteria:

\[68Ga\]Ga DOTA-5G and \[177Lu\]Lu DOTA-ABM-5G therapy Exclusion Criteria:

1. Participants with Class 3 or 4 NYHA Congestive Heart Failure
2. Clinically significant bleeding within two weeks prior to trial. entry (e.g. gastrointestinal bleeding, intracranial bleeding)
3. Pregnant or lactating women
4. Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e., larger than what is required for placement of a central venous access, percutaneous feeding tube, or biopsy) within 28 days prior to study day 1 or anticipated surgery within the subsequent 6 weeks
5. Has an additional active malignancy requiring therapy within the past 2 years (other than early stage, surgically managed basal and squamous skin cancer and in situ malignancies of the breast and cervix)
6. Active, uncontrolled bacterial, viral, or fungal infection(s) despite systemic therapy
7. Psychiatric illness/social situations that would interfere with compliance with study requirements
8. Cannot undergo PET/CT or SPECT/CT scanning because of weight limits (350 lbs.)
9. Known interstitial lung disease or pre-existing pulmonary fibrosis
10. INR \>2.0: PTT\>15 seconds above ULN