gallium-68 labeled lm3 pet/ct in neuroendocrine tumors

Conditions: Neuroendocrine Tumors

Summary: 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.