Somatostatin Receptor Type 2 as an Imaging and Treatment Target for Thyroid Cancer.

Abstract

HomeRadiology: Imaging CancerVol. 3, No. 3 PreviousNext Research HighlightsFree AccessSomatostatin Receptor Type 2 as an Imaging and Treatment Target for Thyroid CancerAdeline N. BoettcherAdeline N. BoettcherAdeline N. BoettcherPublished Online:May 28 2021https://doi.org/10.1148/rycan.2021219009MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Take-Away Points■ Major Focus: To assess somatostatin receptor type 2 (SSRT2) expression in metastatic thyroid cancer and the feasibility of using an Evans blue (EB) analog conjugated to DOTA-0-Tyr-octreotate (DOTA-TATE), called DOTA-EB-TATE, for imaging and treatment.■ Key Result: DOTA-EB-TATE had higher tumor uptake than other somatostatin (SST) analogs.■ Impact: DOTA-EB-TATE could be further developed as a therapeutic agent for enhanced treatment of metastatic thyroid cancer.SSRT2 is a receptor commonly overexpressed in tumors. As such, ligands that target this receptor could be used for theranostic applications. DOTA-TATE and DOTA-Tyr-ocretotide (DOTA-TOC) are both clinically available somatostatin (SST) analogs that bind to SSRT2. These agents can be linked to radioligands for both imaging and therapeutic applications. Recent research in this area has shown that the incorporation of an EB analog, which binds to albumin, has higher tumor uptake and residence time than tracers that do not have EB. Some have called this mechanism «albumin hitchhiking« to improve the pharmacokinetics of administered drugs and imaging tracers (1).Thakur and colleagues assessed SSRT2 expression in human thyroid tumors from The Cancer Genome Atlas, as well as by gallium 68 (68Ga) DOTA-TATE PET/CT imaging in patients with radioactive iodine nonavid metastatic differentiated thyroid cancer and medullary thyroid cancer. Additionally, in mouse xenograft models, the authors investigated the efficacy of using DOTA-EB-TATE for characterization and treatment of tumors compared with DOTA-TATE and DOTA-JR11 (an SSRT2 antagonist with high binding affinity).In all, they found that thyroid tumors had higher expression of SSRT2 compared with normal thyroid tissue and that most patients with metastatic thyroid cancer exhibited positive 68Ga-DOTA-TATE uptake, indicating that these tumors expressed SSRT2. In different mouse xenograft models, yttrium 86 DOTA-EB-TATE consistently had higher uptake in both the primary tumor and metastatic sites compared with 68Ga-DOTA-TATE and 68Ga-DOTA-JR11. Next, lutetium 177 (177Lu)-DOTA-EB-TATE treatment efficacy was compared with 177Lu-DOTA-TATE and 177Lu-DOTA-JR11. Administration of 177Lu-DOTA-EB-TATE resulted in significant tumor growth reduction compared with the other two SST analogs.The results from this study support further investigation into targeting SSRT2-positive thyroid tumors, as well as to assess EB analog conjugates for enhanced therapeutic delivery.Highlighted ArticleThakur S, Daley B, Millo C, et al. 177Lu-DOTA-EB-TATE, a radiolabeled analogue of somatostatin receptor type 2, for the imaging and treatment of thyroid cancer. Clin Cancer Res 2021;27(1399):1409. doi: https://doi.org/10.1158/1078-0432.CCR-20-3453Reference1. Ehlerding EB, Lan X, Cai W. “Albumin hitchhiking” with an Evans blue analog for cancer theranostics. Theranostics. Ivyspring International Publisher; 2018;8(3):812–814. Google ScholarArticle HistoryPublished online: May 28 2021 FiguresReferencesRelatedDetailsRecommended Articles Radiotheranostics in Cancer Diagnosis and ManagementRadiology2018Volume: 286Issue: 2pp. 388-400Invited Commentary: Nuclear Theranostics—The Path ForwardRadioGraphics2020Volume: 40Issue: 6pp. 1741-1742Theranostics in Nuclear Medicine: Emerging and Re-emerging Integrated Imaging and Therapies in the Era of Precision OncologyRadioGraphics2020Volume: 40Issue: 6pp. 1715-174068Ga Fibroblast Activation Protein Inhibitor PET/CT in the Detection of Metastatic Thyroid Cancer: Comparison with 18F-FDG PET/CTRadiology2022Volume: 304Issue: 2pp. 397-405Current Concepts in the Molecular Genetics and Management of Thyroid Cancer: An Update for RadiologistsRadioGraphics2016Volume: 36Issue: 5pp. 1478-1493See More RSNA Education Exhibits Practical Strategies to Improve the Use of PET CT in Thyroid CancerDigital Posters2019Differentiated Thyroid Carcinoma Radioiodine Refractory Patients: How Can FDG-PET/CT Help in the Theranostic Era?Digital Posters2018Theranostic Nuclear Medicine: Past, Present, and FutureDigital Posters2020 RSNA Case Collection Dedifferentiated Thyroid CancerRSNA Case Collection2020TI-RADS 5 NoduleRSNA Case Collection2022Papillary Thyroid CarcinomaRSNA Case Collection2022 Vol. 3, No. 3 Metrics Altmetric Score PDF download