Evaluation of [⁶⁸Ga/¹⁷⁷Lu]HT547: Safety, Biodistribution, and Dosimetry in Solid Tumors

Evaluation of the Safety, Biodistribution and Human Dosimetry of [68Ga]Ga-HT547 PET/CT and [177Lu]Lu-HT547 SPECT/CT in the Clinical Diagnosis of Solid Tumor Patients

Urokinase plasminogen activator receptor (uPAR), the cell-surface receptor for its ligand uPA, plays a critical role in regulating cell migration and invasion-key drivers of cancer progression. This study aims to evaluate a novel uPAR-targeting radiopharmaceutical pair: the diagnostic agent [⁶⁸Ga]Ga-HT547 and the therapeutic agent [¹⁷⁷Lu]Lu-HT547. In patients with breast cancer, head and neck cancer, pancreatic cancer, or glioma, we will assess the diagnostic performance and biodistribution of these tracers using [⁶⁸Ga]Ga-HT547 and [¹⁷⁷Lu]Lu-HT547 SPECT/CT.

Inclusion Criteria:

1. Willing and able to communicate with the investigator, understand and comply with trial requirements, voluntarily participate in the trial, and provide written informed consent.
2. Aged 18 years or older, regardless of gender.
3. Expected survival of at least 3 months.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
5. Patients with solid tumors (breast cancer, head and neck cancer, pancreatic cancer, or brain glioma) confirmed by histology or cytology.
6. Radiographic evidence of disease progression within 12 months prior to screening (according to RECIST 1.1 criteria).
7. At least one measurable target lesion according to RECIST 1.1 criteria.
8. Positive uptake in the target lesion on ⁶⁸Ga-HT547 Positron Emission Tomography (PET) scan, with SUV ≥ 4.
9. Recovery from toxicities related to prior therapy to ≤ Grade 1 or baseline (except for alopecia, vitiligo, etc.).
10. For subjects of childbearing potential: Agreement to remain abstinent or use effective contraception (including intrauterine devices, etc.) from signing the ICF until at least 24 weeks after the last dose.

Exclusion Criteria:

1. Pregnant or breastfeeding women, or women with a positive baseline pregnancy test.

2. History of severe allergic reaction to any component of the investigational drug injection.

3. Received blood transfusion within 4 weeks prior to screening to meet the enrollment criteria.

4. Received immunotherapy, chemotherapy, radiotherapy, or other anti-tumor therapy within 4 weeks prior to the first dose.

5. Received any investigational drug within 28 days prior to the first dose, or concurrent participation in another clinical study (except: participation in an observational, non-interventional study, or being in the follow-up phase of an interventional study).

6. History of other known malignancies within the past 5 years.

7. Presence of symptomatic or unstable third-space effusions (e.g., pleural effusion, ascites, pericardial effusion) requiring repeated drainage.

8. Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.

9. Inadequate organ function (meeting any of the following):

   1. Bone marrow reserve: Neutrophil count < 1.5 x 10⁹/L, or platelet count < 100 x 10⁹/L, or hemoglobin < 90 g/L.
   2. Liver function: AST/ALT > 3 x ULN (> 5 x ULN for subjects with liver metastases), or albumin ≤ 2.8 g/dL, or total bilirubin > 1.5 x ULN.
   3. Renal function: Serum creatinine > 1.5 x ULN and creatinine clearance < 60 mL/min (calculated by Cockcroft-Gault formula).

10. Severe cardiovascular clinical diseases or symptoms that may increase subject safety risk, including:

    1. Congestive heart failure (New York Heart Association [NYHA] class > II) within the past year.
    2. Unstable angina within the past year.
    3. Myocardial infarction within the past year.
    4. Clinically significant malignant arrhythmia (except for atrial fibrillation, paroxysmal supraventricular tachycardia).
    5. Presence of clinically significant QTcF prolongation (QTcF > 470 ms, calculated by Fridericia's formula).

11. Clinically significant bleeding (e.g., gastrointestinal bleeding, intracranial hemorrhage) within 14 days prior to the first dose.

12. Major surgery or significant trauma within 28 days prior to the first dose.

13. Any other condition that, in the investigator's judgment, may increase safety risk or interfere with its interpretation.

14. Inability of the subject to understand and comply with study instructions and requirements.

15. Any other situation deemed inappropriate by the investigator.