Biodistribution and radiation dose estimates for 68Ga-DOTA-JR11 in patients with metastatic neuroendocrine tumors
Somatostatin receptor antagonists have shown promise for imaging neuroendocrine tumors (NETs) in preclinical studies, but clinical data is still very limited. In this study, we assess the feasibility of using the novel somatostatin antagonist 68Ga-DOTA-JR11 for PET imaging of NETs.
Twenty patients with advanced NETs underwent whole-body PET/CT imaging 60 min after injection of 169 MBq (median) 68Ga-DOTA-JR11 as part of a prospective study. Volumes of interest were drawn around up to four 68Ga-DOTA-JR11-avid lesions per patient (with uptake greater than liver) and standardized uptake values were estimated. Additionally, target-to-normal tissue ratios were calculated. A subset of six patients had additional imaging (25-min dynamic scan of the upper abdomen including, at least partly, cardiac left ventricle, liver, spleen, and kidney, and a whole-body PET/CT scan at 30 min post-injection) to determine the time course of tracer distribution and facilitate radiation dose estimates. Absorbed doses were calculated using OLINDA/EXM 1.0.
In contrast to the known biodistribution of somatostatin receptor agonists, little or no uptake above background was seen in the pituitary gland, spleen, adrenals, and uninvolved liver; e.g., median spleen SUVmean 1.4 (range: 0.7–1.8), liver SUVmean 1.1 (0.7–1.9). A total of 42 tumor lesions were analyzed with median SUVmax 13.0 (range: 2.9–94), TNR blood 9.3 (1.8–87), TNR spleen 4.9 (1.9–48), TNR kidney 2.2 (0.52–28), and TNR liver 10.5 (2.3–107). Tumor uptake reached plateau levels by 20-30 min post-injection. The highest absorbed dose estimates (mGy/MBq) to normal tissues were: urinary bladder wall (0.30; SD 0.06) and kidneys (0.050; SD 0.013). The effective dose (ICRP 103) was 0.022 (SD 0.003) mSv/MBq.
68Ga-DOTA-JR11 demonstrated rapid tumor uptake, high tumor/background ratios, and rapid clearance from blood. The low liver background is advantageous and may facilitate detection of liver metastases. Dosimetric data compare favorably with published data for 68Ga-DOTATATE and 68Ga-DOTATOC.
KeywordsSomatostatin receptor antagonists JR11 PET/CT Neuroendocrine tumors
This study was supported in part by the Geoffrey Beene Cancer Research Center at MSK and the MSK Radiochemistry and Molecular Imaging Probe Core, which is funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. We gratefully acknowledge funding by Caring for the Carcinoid/NETRF. SK was supported in part by the NIH/NCI Paul Calabresi Career Development Award for Clinical Oncology K12 CA184746. The precursor used in this study was provided by Ipsen.
We gratefully acknowledge Rashid Ghani and members of the Nuclear Medicine Pharmacy; nuclear medicine nurses Ann Longing and Louise Harris for their help in patient management; RSAs Alicia Lashley, Hanh Pham, and Martha Ziolkowska and Clinical Research Manager Bolorsukh Gansukh for their excellent support with patient flow and protocol management; the radiation safety officers and nuclear medicine technologists for their excellent technical assistance; and members of the Department of Medicine at MSK for patient referral. We also thank Leah Bassity for her assistance in editing this manuscript.
This study was supported in part by the Geoffrey Beene Cancer Research Center at MSK, and the MSK Radiochemistry and Molecular Imaging Probe Core was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. We gratefully acknowledge the funding by Caring for the Carcinoid/NETRF. SK was supported in part by NIH/NCI Paul Calabresi Career Development Award for Clinical Oncology K12 CA184746. The precursor used in this study was provided by Ipsen.
Compliance with ethical standards
Conflict of interest
DR was a member of the Advisory Board for Ipsen, Novartis, Advanced Accelerator Applications (AAA), and Lexicon Pharmaceuticals and has received research funding from Ipsen and Novartis. LB acted as a consultant for Advanced Accelerator Applications (AAA) and Ipsen. WW has served as a consultant for Endocyte, Ipsen, and Piramal Imaging. JAD has served as a consultant to WILEX AG, Algeta ASA, and Janssen Pharmaceuticals, Inc. SK, NP, BJB, SKL, and JSL declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed written consent was obtained from all individual participants included in the study.
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