Somatostatin Receptor Imaging and Theranostics: Current Practice and Future Prospects

Abstract

A new era of precision diagnostics and therapy for patients with neuroendocrine neoplasms began with the approval of somatostatin receptor (SSTR) radiopharmaceuticals for PET imaging followed by peptide receptor radionuclide therapy (PRRT). With the transition from SSTRbased g-scintigraphy to PET, the higher sensitivity of the latter raised questions regarding the direct application of the planar scintigraphy-based Krenning score for PRRT eligibility. Also, to date, the role of SSTR PET in response assessment and predicting outcome remains under evaluation. In this comprehensive review article, we discuss the current role of SSTR PET in all aspects of neuroendocrine neoplasms, including its relation to conventional imaging, selection of patients for PRRT, and the current understanding of SSTR PET-based response assessment. We also provide a standardized reporting template for SSTR PET with a brief discussion.

Nephrotoxicity after radionuclide therapies

“…The tumor uptake of a radiopharmaceutical depends primarily on the delivery of the radio-tracer to the target site, expression of the relevant receptors/ transporters and the target-specific affinity of the radiopharmaceutical [94] . Decreased perfusion can be one of the major limiting factors for reduced tracer uptake and hence, reduced tumor absorbed doses.…”

Molecular imaging phenotyping for selecting and monitoring radioligand therapy of neuroendocrine neoplasms

“…For lesions > 2 cm, the scores of 3–4 are deemed adequate for considering PRRT. However, for lesions smaller than 2 cm, the PET-based scoring might overestimate compared to the original Krenning score [ 4 ]. In principle, PRRT should not be considered in patients with the majority of lesions demonstrating no or low avidity on SSTR PET.…”

“…SSTR sub-types 2, 3 and 5 are most commonly expressed on the NEN cells with the dominant subtype 2 being primarily targeted for molecular imaging using positron emission tomography (PET) or single-photon emission computed tomography (SPECT) [ 3 ]. SSTR PET using 68 Ga- or 64 Cu- labeled somatostatin analogs (DOTANOC, DOTATATE, DOTATOC, SARTATE) has superior diagnostic performance in comparison to SPECT with 111 In-Pentetreotide (Octreoscan), with the former being the modality of choice for functional imaging of the NETs [ 4 , 5 ]. 18 F-Fluorodeoxyglucose ( 18 F-FDG), the ubiquitous radiotracer for oncologic PET imaging has a limited role in the detection of low-grade, well-differentiated NENs.…”

“…These are primarily higher grade NENs, which have imaging features similar to other aggressive cancers in having augmented glycolytic metabolism. Accordingly, 18 F-FDG can provide complementary information, particularly by the detection of more aggressive and poorly-differentiated tumour foci, that can co-exist in patients with the otherwise low-grade disease [ 4 ]. Alternative molecular targets are available for specific subcategories of NEN.…”

“…Peptide receptor radionuclide therapy (PRRT), most widely available with 177 Lu-DOTATATE, has emerged as a valuable treatment modality for metastatic NENs and showed superior outcomes over the standard-of-care in patients with inoperable or advanced and progressive midgut NETs in a phase-3 randomized controlled trial (NETTER-1) [ 15 ]. However, the treatment outcomes of PRRT depend heavily on the adequacy of patient selection, performed using a combination of imaging and non-imaging techniques, as highlighted previously [ 4 , 16 , 17 ].…”