Head-to-Head Comparison of ⁶⁸Ga-DOTA-JR11 and ⁶⁸Ga-DOTATATE PET/CT in Patients with Metastatic, Well-Differentiated Neuroendocrine Tumors: A Prospective Study

Abstract

Ga-DOTA-JR11 is a somatostatin receptor subtype 2-specific antagonist used for PET/CT imaging. The purpose of this study was to compare 68 Ga-DOTA-JR11 and 68 Ga-DOTATATE PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors. Methods: Patients with histologically proven, metastatic or unresectable, well-differentiated neuroendocrine tumors were prospectively recruited to this study. Each patient received an intravenous injection of 68 Ga-DOTATATE (155 ± 52 MBq) on the first day and 68 Ga-DOTA-JR11 (148 ± 52 MBq) on the second day. Whole-body PET/CT scans were performed at 40-60 min after injection on the same scanner. Physiologic normal-organ uptake, lesion numbers, and lesion uptake were compared. Results: Thirty-one patients were prospectively enrolled in the study. The SUV max of the spleen, renal cortex, adrenal glands, pituitary glands, stomach wall, normal liver parenchyma, small intestine, pancreas, and bone marrow was significantly lower on 68 Ga-DOTA-JR11 than on 68 Ga-DOTATATE PET/CT (P , 0.001). 68 Ga-DOTA-JR11 detected significantly more liver lesions (552 vs. 365, P 5 0.001) but fewer bone lesions (158 vs. 388, P 5 0.016) than 68 Ga-DOTATATE. The target-to-background ratio of liver lesions was significantly higher on 68 Ga-DOTA-JR11 (7.7 ± 5.4 vs. 3.4 ± 2.0, P , 0.001). 68 Ga-DOTA-JR11 and 68 Ga-DOTATATE PET/CT showed comparable results for primary tumors and lymph node metastases on both patientbased and lesion-based comparisons. Conclusion: 68 Ga-DOTA-JR11 performs better in detecting liver metastases, with a better tumor-tobackground ratio, whereas 68 Ga-DOTATATE may outperform 68 Ga-DOTA-JR11 in the detection of bone metastases. However, the lower somatostatin receptor subtype 2 affinity of 68 Ga-DOTA-JR11 than of 177 Lu-DOTA-JR11 may limit its role as a diagnostic pair for the theranostic approach with 177 Lu-DOTA-JR11.

177Lu-DOTA-EB-TATE, a Radiolabeled Analogue of Somatostatin Receptor Type 2, for the Imaging and Treatment of Thyroid Cancer

“…We also compared the therapeutic efficacy of 177 Lu-labeled DOTA-TATE, DOTA-JR11, and DOTA-EB-TATE, documenting the superiority of the latter in the mouse model characterized by high SSTR2 expression. There are several studies that suggested the superiority of SST antagonists over SST agonists (16,40,41). In our study, no significant difference was observed in the uptake of octreotate (TATE-agonist) vs JR11 (antagonist) linked to the same chelator (DOTA) in the tested mice models.…”

Targeted Cancer Therapy: What’s New in the Field of Neuroendocrine Neoplasms?

“…Radiolabeled SSTR2 antagonists, such as 177Lu-satoreotide tetraxetan, have shown higher tumor uptake, independent of SSTR activation, and greater tumor-to-organ ratios than agonists in preclinical models [ 160 ]. SSTR antagonists such as 68Ga-DOTA-JR11, [18F] AlF-NOTA-JR11, 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3, have demonstrated great sensitivity for the detection of NENs, potentially superior to [68Ga]Ga-DOTATATE [ 161 , 162 , 163 , 164 ]. A phase I study evaluated the efficacy and safety of 177Lu-satoreotide tetraxetan in 20 patients with advanced SSTR2-positive NETs [ 165 ].…”

“…Patients that have received prior alkylating chemotherapy are at greater risk of developing MDS/acute leukemia following PRRT [158,159] Radiolabeled SSTR2 antagonists, such as 177Lu-satoreotide tetraxetan, have shown higher tumor uptake, independent of SSTR activation, and greater tumor-to-organ ratios than agonists in preclinical models [160]. SSTR antagonists such as 68Ga-DOTA-JR11, [18F] AlF-NOTA-JR11, 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3, have demonstrated great sensitivity for the detection of NENs, potentially superior to [68Ga]Ga-DOTATATE [161][162][163][164].…”

Use of 18F-FDG PET/CT to differentiate ectopic adrenocorticotropic hormone-secreting lung tumors from tumor-like pulmonary infections in patients with ectopic Cushing syndrome

“…All scans were obtained in a three-dimensional model. 68 Ga-DOTA-TATE PET/CT Study The 68 Ga-DOTATATE was produced following our previously published procedure [13]. The study was carried out on a PET/CT scanner (Siemens Co.).…”