Impact and Potential Pitfalls of Ga-68 DOTATATE PET/CT

1221 Introduction: Neuroendocrine tumors (NETs) are a heterogeneous class of rare tumors which have been increasing in incidence, partly due to improved diagnosis.[1] Most NETs do not secrete hormones, such that the particular symptoms caused by a given NET are often non-specific, including abdominal discomfort arising from mass effects, or typical NET symptoms of diarrhea or flushing.[1] Early diagnosis of NET is pivotal for a successful management leading clinicians to the most optimal treatment option for an individual patient. In addition to clinical signs and symptoms, chromogranin A (CgA) as a sensitive tumor marker for NETs provide a diagnostic sensitivity of 70%-85%. However, this laboratory test is not sufficient for identification of tumor sites and also may not be as specific as desired because proton pump inhibitor therapy, atrophic gastritis, renal insufficiency, and numerous other conditions can cause elevated levels.[1] Imaging modalities, including CT, MRI, endoscopy, and endosonography have facilitated the diagnosis of suspected NETs. However, molecular imaging through targeting somatostatin receptors (SSTR) has allowed for more specific NET detection.[1] In-111 octreotide has been widely used in NET diagnosis, but a half-life of 67 hours, image acquisition at 24 and 48 hours, and its low sensitivity for primary NET in the range of 35%- 80% are its main drawbacks.[2] Ga-68 DOTATATE has been approved by the FDA on 6/1/2016 as a PET/CT probe.[3] Ga-68 DOTATATE targets mainly somatostatin receptor subtype 2 (SSTR2) and provides superior image quality, lower radiation dosimetry, and greater patient convenience compared to In-111 octreotide.[4] Ga-68 DOTATATE PET/CT has an estimated sensitivity of 90.9% (95% confidence interval, 81.4%-96.4%), and specificity of 90.6% (95% confidence interval, 77.8%-96.1%).[4] This molecular diagnostic tool through the Krenning scoring system has also been integral in the selection as well as follow-up of patients who undergo peptide receptor nuclide therapy (PRRT), with Lu-177 DOTATATE. EDUCATIONAL OBJECTIVES 1) Clinical indications for Ga-68 DOTATATE PET/CT 2) Optimal PET/CT imaging protocol 3) Patient preparation for Ga-68 DOTATATE 4) Physiologic distribution of Ga-68 DOTATATE and the suggested interpretation scheme 5) Case examples showing pitfalls and potential sources for false positive and negatives 6) Clinical examples of Ga-68 DOTATATE PET/CT, in comparison to In-111 Octreotide SPECT/CT in selected cases and its attendant clinical impact. SUMMARY Patients with a NET suspected on the basis of clinical symptoms, elevated levels of tumor markers, and/or equivocal findings on other diagnostic modalities have greatly benefited from Ga-68 DOTATATE PET/CT, given its proven superiority to all existing imaging modalities that are in clinical use for patients with NET. However, imagers should be fully cognizant of using the correct imaging protocol, patient preparation, right interpretation scheme, potential pitfalls and expected clinical impact for improving clinical care of NET patients.