Gallium-68 Labeled LM3 PET/CT in Neuroendocrine Tumors

LM3 is a novel somatostatin receptor antagonist, while Gallium-68 DOTATATE is a typical somatostatin receptor agonist, This study is to evaluate the safety, biodistribution, dosimetry, and lesion detection ability of Gallium-68 labeled somatostatin receptor antagonist LM3 for the diagnostic imaging of metastatic, well-differentiated neuroendocrine tumors using positron emission tomography / computed tomography (PET/CT).

The results will be compared between antagonist Gallium-68 labeled LM3 and agonist Gallium-labeled DOTATATE in the same group of patients.

It will also be compared between the two different antagonists, Gallium-68 DOTA-LM3 and Gallium-68 NODAGA-LM3, in two parallel-designed arms.

Patients with histologically confirmed metastatic, well-differentiated neuroendocrine tumors will be recruited in this study.

All patients will be randomized into two groups: Gallium-68 NODAGA-LM3 group and Gallium-68 DOTA-LM3 group.

The study will be divided into the following 2 parts:

Part ONE, which will enroll 16 patients (8 in each group), focuses on the safety evaluation, biodistribution, and dosimetry. In Part A, patients will undergo serial whole-body PET/CT scans at multiple time points (5m, 10m, 20m, 40m, 1h, 2h) after administering 40ug/150-200MBq Gallium-68 NODAGA-LM3 or Gallium-68 DOTA-LM3 (according to their group).

Part TWO, which will enroll 24 patients (12 in each group) and follows Part A study, focuses on lesion detection ability. In Part B, patients will undergo one whole-body PET/CT scan at 1 hour after administering 40ug/150-200MBq Gallium-68 NODAGA-LM3 or Gallium-68 DOTA-LM3 (according to their group).

All patients need to do a Gallium-68 DOTATATE PET/CT scan (40ug/150-200MBq, 1h post-injection) for comparison on the next day.

Eligibility Criteria:
Inclusion Criteria:

* Written informed consent.
* Patients of either gender, aged ≥ 18 years.
* Histologically confirmed diagnosis of Metastatic, well-differentiated neuroendocrine tumor.
* A diagnostic computed tomography (CT) or magnetic resonance imaging (MRI) of the tumor region within the previous 6 months prior to dosing day is available.
* At least 1 measurable lesion based on RECIST v1.1.
* Blood test results as follows (White blood cell: ≥ 3\*10\^9/L, Hemoglobin: ≥ 8.0 g/dL, Platelets: ≥ 50x10\^9/L, Alanine aminotransferase / Aspartate aminotransferase / Alkaline phosphatase: ≤ 5 times upper limit od normal (ULN), Bilirubin: ≤ 3 times ULN)
* Serum creatinine: within normal limits or \< 120 μmol/L for patients aged 60 years or older.
* Calculated Glomerular filtration rate (GFR) ≥ 45 mL/min.

Exclusion Criteria:

* Known hypersensitivity to Gallium-68, to NODAGA, to DOTA, to LM3, to TATE or to any of the excipients of Gallium-68 DOTA-LM3, Gallium-68 NODAGA-LM3 or Gallium-68 DOTATATE.
* Presence of active infection at screening or history of serious infection within the previous 6 weeks.
* Therapeutic use of any somatostatin analog, including long-acting Sandostatin (within 28 days) and short-acting Sandostatin (within 2 days) prior to study imaging. If a patient is on long-acting Sandostatina, then a wash-out phase of 28 days is required before the injection of the study drug. If a patient is on short-acting Sandostatin, then a wash-out phase of 2 days is required before the injection of the study drug.
* Any neuroendocrine tumor-specific treatment between antagonist and agonist scans.
* Prior or planned administration of a radiopharmaceutical within 8 half-lives of the radionuclide used on such radiopharmaceutical including at any time during the current study.
* Pregnant or breast-feeding women.
* Current history of any malignancy other than neuroendocrine tumor; patients with a secondary tumor in remission of \> 5 years can be included.
* Any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.