The Role of 68Ga-DOTATATE Positron Emission Tomography/Computed Tomography in Well-Differentiated Neuroendocrine Tumors: A Case-Based Approach Illustrates Potential Benefits and Challenges

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In 1994, the octreotide scan (somatostatin receptor [SSTR] scintigraphy with 111In-pentetreotide) was approved for imaging of neuroendocrine tumors (NETs) based on studies suggesting that octreotide scans were better at localizing and staging NETs when compared with conventional cross-sectional imaging (computed tomography [CT] and/or magnetic resonance imaging [MRI]).1 Although octreotide scans have the advantage of whole-body visualization, they also have limitations, including low spatial resolution, uptake of the radiotracer in normal organs, and increased burden on patients requiring multiple visits and scans over 2 to 3 days.2
In 2011, our group evaluated the clinical use of octreotide scans in detecting additional NET lesions compared with conventional cross-sectional imaging.3 In our institutional series of 121 patients, cross-sectional imaging detected more NET soft tissue lesions than octreotide scans. Octreotide scans, however, identified more asymptomatic and unsuspected bone metastases. Based on our findings, we concluded that advances made in cross-sectional imaging changed the relative use of octreotide scans. We advocated for the use of octreotide scans to test for the presence of the SSTR but not to follow the extent of disease. Although our report was controversial, a subsequent investigation evaluated the clinical use of octreotide scans in the diagnosis and management of NET patients and also concluded that it did not alter surgical management.4 Given these findings, as indicated in the National Comprehensive Cancer Network (NCCN) guidelines, octreotide scans are not recommended for surveillance after resection, as an adjunct for tumor staging, or for monitoring the status of advanced disease.
In recent years, the development of novel functional imaging radioisotopes using positron emission tomography (PET) tracers (the gallium-68 [68Ga] DOTA-peptides: 68Ga-DOTATOC, 68Ga-DOTATATE, 68Ga-DOTANOC) has demonstrated promising results for the visualization of NET lesions in comparison with conventional octreotide scans.5–12 Unlike octreotide scans, 68Ga imaging is a single-day procedure with higher spatial resolution, improved dosimetry, and the ability to semiquantify the activity in a given region as the standard uptake value.13
On June 1, 2016, the US Food and Drug Administration (FDA) approved Netspot, the first kit for the preparation of 68Ga-DOTATATE injection for PET imaging, as a diagnostic tool to help clinicians determine the location and extent of NETs. With FDA approval, there has been gradual increase in access to 68Ga-DOTATATE PET/CT in the United States, and this scan is now included in the NCCN guidelines as a form of SSTR-based imaging. As availability of 68Ga-DOTATATE PET/CT increases, it is believed that this imaging will become the criterion standard, replacing octreotide scans for the evaluation of SSTR-positive disease in patients with NETs.
Despite the advances in SSTR functional imaging, it remains unclear how 68Ga-DOTATATE PET/CT will change our clinical practice. Will this scan be used preoperatively to define the extent of disease and alter decisions to operate? Will it replace cross-sectional imaging? Will increased detection of disease alter medical management and importantly, should it? All of these questions remain unanswered. Given the current lack of prospective data to address these questions, we have selected patient cases that we believe illustrate the potential benefits and challenges in using 68Ga-DOTATATE PET/CT in the routine clinical setting.

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