Evaluation of 68Gallium-DOTATATE PET/CT for Detecting Neuroendocrine Tumors

Background:

• Neuroendocrine tumors (NETs) are rare malignancies occurring in the gastrointestinal tract, islets of the pancreas, lung, adrenal medulla and thyroid C-cells.
• Their incidence has increased over the last decade, with an incidence of 6 per 100,000 persons a year and they represent 0.46% of all malignancies.
• Most NETs are sporadic, but they can be part of familial cancer syndromes such as multiple endocrine neoplasia type 1 (MEN1), MEN2, and neurofibromatosis type 1 (NF1) or Von Hippel-Lindau (VHL) syndrome.
• Surgical resection remains the only curative treatment option for patients with NETs but 80% of patients are diagnosed with advanced (metastatic, locally inoperable, or recurrent) disease.
• The main prognostic factor in patients with NET is the extent of disease.
• The best imaging technique for detecting unknown primary and metastatic NETs has yet to be determined.
• NET cells express somatostatin receptors that can be targeted with radiolabeled 68Gallium-DOTATATE (Octreotate) for imaging purposes.
• The primary goal of this protocol is to determine the accuracy of a new somatostatin receptor targeted imaging technique, using 68Gallium-DOTATATE PET/CT to detect unknown primary and metastatic NETs.

Objectives:

-To determine the accuracy of 68Gallium-DOTATATE PET/CT scans in detecting unknown primary and metastatic gastrointestinal and pancreatic neuroendocrine tumors.

Eligibility:

• Patients with:

• suspicion of NET on axial imaging (CT/magnetic resonance imaging (MRI)/fluorodeoxyglucose-positron emission tomography (FDG PET) and/or
• biochemical evidence of NET (serum/urinary) based on elevated levels of chromogranin A, pancreatic polypeptide, neuron-specific enolase, vasoactive intestinal polypeptide, serotonin (urinary 5-HIAA), gastrin, somatostatin, catecholamines, metanephrines, calcitonin, fasting insulin, C-peptide (proinsulin), glucagon and/or
• familial predisposition to NET in patients with multiple endocrine neoplasia type 1 (MEN1) and VHL.
• Age greater than or equal to 18 years of age.
• Patients must be willing to return to National Institutes of Health (NIH) for follow-up.

Design:

• Prospective study.
• A 68Ga-DOTATATE PET/CT scan will be done in patients with suspicious lesions, unknown primary tumor or metastatic gastrointestinal or pancreatic neuroendocrine disease found on anatomic imaging (CT/MRI) or in patients having biochemically active disease.
• Both functional and non-functional solid tumors will be included in this study. Furthermore, asymptomatic and symptomatic, sporadic and familial cases of NETs (such as Von Hippel-Lindau (VHL), MEN1) will be included.
• Demographic, clinical and pathologic data will be collected from the medical record and patient interview for each patient. Data will be stored in a computerized database.
• After their initial on-study evaluation, patients will be staged according to findings on imaging studies with respect to primary tumor site, size and metastases. Surgical resection of NET and/or medical managements will be recommended based on standard practice guidelines. In patients who undergo surgical treatment, the samples will be immediately stored until molecular analysis.
• Follow up will be done yearly for a total duration of 5 years. This includes a yearly imaging study and a biochemical and clinical evaluation, to assess tumor growth and disease progression.
• We estimate that the accrual rate will be 3-10 patients per month; the total accrual period for this study will be 10 months to 3 years.

• INCLUSION CRITERIA:
• Patients with (any one of #1, #2, and/or #3):

• Suspicion of neuroendocrine tumors (NET) on axial imaging (computed tomography (CT)/magnetic resonance imaging (MRI)/fluorodeoxyglucose (FDG) positron emission tomography (PET) and/or
• biochemical evidence of neuroendocrine tumor (serum/urinary) based on elevated levels of chromogranin A, pancreatic polypeptide, neuron-specific enolase, vasoactive intestinal polypeptide, serotonin (urinary 5-HIAA), gastrin, somatostatin, catecholamines, metanephrines, calcitonin, fasting insulin, C-peptide (proinsulin), glucagon and/or
• familial predisposition to NET in patients with multiple endocrine neoplasia type 1 (MEN1) and Von Hippel-Lindau (VHL) (symptomatic and/or asymptomatic cases; with biochemical or anatomic imaging evidence of disease).
• Age greater than or equal to 10 years of age.
• For females: Negative urine pregnancy test OR post-menopausal for at least 2 years OR patient has had a hysterectomy.
• Patients must be willing to return to National Institutes of Health (NIH) for follow-up.
• Ability of subject or Legally Authorized Representative (LAR) (if the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable) to understand and the willingness to sign a written informed consent document indicating that they are aware of the investigational nature of this study.

Exclusion criteria

• Patients unwilling to undergo serial non-invasive imaging.
• Pregnant or lactating women: Pregnant women are excluded from this study because the effects of (68)Ga-DOTATATE in pregnancy are not known. Because there is an unknown but potential risk for adverse events in nursing infants secondary to administration of

(68)Ga-DOTATATE in the mother, breastfeeding should be discontinued for at least one day if the mother receives (68)Ga-DOTATATE.

• Patients that have recognized concurrent active infection,
• Patients with the use of any investigational product or device, excluding 18F-dihydroxyphenylalanine (F-DOPA) scans, within 30 days prior to dosing.