Biodistribution and radiation dose estimates for 68Ga-DOTA-JR11 in patients with metastatic neuroendocrine tumors

Eur J Nucl Med Mol Imaging. 2019 Mar;46(3):677-685. doi: 10.1007/s00259-018-4193-y. Epub 2018 Oct 29.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: JR11; Neuroendocrine tumors; PET/CT; Somatostatin receptor antagonists.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Feasibility Studies
  • Female
  • Gallium Radioisotopes / adverse effects
  • Gallium Radioisotopes / pharmacokinetics*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neuroendocrine Tumors / diagnostic imaging*
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / pathology*
  • Positron Emission Tomography Computed Tomography* / adverse effects
  • Radiation Dosage*
  • Radiometry
  • Safety
  • Tissue Distribution
  • Young Adult

Substances

  • Gallium Radioisotopes