SAT-575 Radiolabeled Somatostatin Receptor Analog 86Y-EB-TATE is Characterized by Superior Tumor Uptake Compared to 68Ga-DOTA-TATE and 68Ga-DOTA-JR11 in Thyroid Cancer Mice Models

Abstract

Background: Differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC) are characterized by the overexpression of somatostatin receptor type 2 (SSTR2). There are limited data on the use of SSTR2 as a molecular target for imaging and treatment of DTC and MTC. The goal of our study was to compare the diagnostic accuracy of three different radiolabeled SSTR2 analogs in DTC and MTC mouse models: JR11, an antagonist; DOTATATE, an agonist; and EB-TATE, a novel modified agonist characterized by a longer half-life in the blood. Methods: SSTR2 expression was analyzed in two DTC cell lines (BCPAP and FTC133) and one MTC cell line (TT) by RT-PCR and immunoblotting. A rat pancreatic cell line (AR42J), characterized by intrinsically high SSTR2 expression, was used as a positive control. A metastatic (MT) mouse model was generated using immunocompromised mice which develop lung and liver metastases after tail vein injection of FTC133 and BCPAP cells. Subcutaneous (SC) xenograft mice models were generated by injecting FTC133, BCPAP, TT, and AR42J cells. The fast-growing FTC133 and AR42J cells formed soft, sizable tumors in 2 weeks, while BCPAP and TT cells formed very solid tumors after 4 and 8 weeks, respectively. Maximum standard uptake value of 68Ga-DOTATATE, 86Y-EB-TATE, and 68Ga-DOTA-JR11 (IPSEN®) was compared in each mouse in MT and SC models by PET/CT. Results: Among thyroid cancer cell lines, TT cells were characterized by the highest SSTR2 expression at the mRNA level compared with BCPAP (p<0.001) and FTC133 (p<0.001). At the protein level, BCPAP and TT cells were characterized by similar SSTR2 expression and FTC133 cells had the lowest expression. Among examined radiolabeled SSTR2 analogs, 86Y-EB-TATE showed the highest tumor uptake in all MT and SC mouse models in comparison to 68Ga-DOTATATE (p< 0.001) and 68Ga-DOTA-JR11, (p<0.001). 68Ga-DOTA-JR11 was characterized by higher tumor uptake than 68Ga-DOTATATE in only the SC FTC133 mouse model (p=0.01). The AR42J mouse model (positive control) had the highest tumor uptake of all three radioactive analogs in comparison to DTC and MTC mice models (p<0.001). Among thyroid cancer mice models, aggressively growing FTC133 tumors were characterized by the highest uptake of 68Ga-DOTA-JR11 and 86Y-EB-TATE compared with slow-growing BCPAP (p<0.01 & p<0.001, respectively) and TT tumors (p<0.05 & p<0.001, respectively) in SC mice models. There was no significant difference in the 68Ga-DOTATATE uptake between FTC133 and BCPAP mice models (p= 0.97), which were characterized by significantly higher uptake than the TT mouse model (p= 0.01 & 0.03, respectively). Conclusion: We show for the first time that a novel SSTR2 analog 86Y-EB-TATE is characterized by superior tumor uptake compared to 68Ga-DOTATATE and 68Ga-DOTA-JR11 in TC mice models. Uptake of the radiolabeled analogs not only depends on SSTR2 expression levels, but also on the tumor aggressiveness.