Molecular imaging in neuroendocrine tumors: recent advances, controversies, unresolved issues, and roles in management

Abstract

Purpose To review recent advances in molecular imaging of neuroendocrine tumors (NETs), discuss unresolved issues, and review how these advances are affecting clinical management. Recent findings Molecular imaging of NETs underwent a number of important changes in the last few years, leading to some controversies, unresolved issues, and significant changes in clinical management. The most recent changes are reviewed in this article. Particularly important is the rapid replacement in somatostatin receptor scintigraphy (SRS) of 111In-DTPA-SPECT/CT by 68Ga-DOTA-peptide-PET/CT imaging, which is now approved in many countries including the US. Numerous studies in many different types of NETs demonstrate the greater sensitivity of 68Ga-DOTA-peptide-PET/CT, its high specificity, and its impact on management. Other important developments in SRS/molecular imaging include demonstrating the prognostic value of both 68Ga-DOTA-peptide-PET/CT and 18F-FDG –PET/CT; how their use can be complementary; comparing the sensitivities and usefulness of 68Ga-DOTA-peptide-PET/CT and 18F-FDOPA PET/CT; introducing new linkers and radiolabeled ligands such as 64Cu-DOTA-peptides with a long half-life, enhancing utility; and the introduction of somatostatin receptor antagonists which show enhanced uptake by NETs. In addition, novel ligands which interact with other receptors (GLP1, Bombesin, CCK, GIP, integrin, chemokines) are described which show promise in the imaging of both NETs and other tumors. Summary Molecular imaging is now required for all aspects of the management of patients with NETs. It results are essential not only for the proper diagnostic management of the patient, but also for assessing whether the patient is a candidate for peptide receptor radionuclide therapy (PRRT) with 177Lu and also for providing prognostic value.

Diagnosis of Zollinger–Ellison Syndrome in the Era of Ppis, Faulty Gastrin Assays, Sensitive Imaging and Limited Access to Acid Secretory Testing

“…However, if SRI is used for imaging with either 68 Ga-DOTATATE PET/CT or 111 In-DTPA-octreotide with SPECT/CT imaging combined instead of a cross-sectional imaging study, the likelihood of ZES is higher but this too is not always diagnostic, because overexpression of somatostatin receptors does occur in certain non-endocrine tumors (breast, prostate, lymphomas, CNS, lung, etc.) [108, 135], non-endocrine tissues, and almost all well-differentiated neuroendocrine tumors [108, 135], even if ZES is absent. There are some specific situations that strongly support a diagnosis of ZES (Table 3) without the presence of a pH measurement but it is essential to realize that PPI therapy clearly confounds the diagnosis in most other scenarios (Table 4).…”

“… (3) SRI can be positive in nonngastrinoma NETs, numerous other tumors and both physiological and pharmacologic processes [see text], so alone is not specfic for gastrinoma[107, 108, 135]. …”

Malignant transformation of glucagonoma with SPECT/CT In-111 OctreoScan features

“…[ 6 ] Another useful purpose of performing SRS is the evaluation of the functional state of the tumor and of the secondary localization, thus providing suitability for therapy with peptide receptor radionuclide therapy (PRRT). [ 22 , 25 ]…”

Neuropeptide G Protein-Coupled Receptors as Oncotargets

“…SST receptor imaging (SRI) was originally approved for the use of 111 In-labeled pentetreotide with SPECT/CT scanning (Octreoscan), which is now replaced by the use of 68 Ga-DOTATATE PET/CT scanning, which has greater resolution, sensitivity and high specificity ( 118 – 122 ). Almost all well differentiated NETs overexpress the somatostatin receptor subtypes (SSTR2 > SSTR5 > SSTR3) that bind this radiolabeled agonist with high affinity ( 118 , 119 , 123 ). A systematic review ( 122 ) demonstrated that the use of 68 Ga-DOTATATE PET/CT scanning changed the management of the patient in a mean of 44% (range, 16–71%).…”