Safety, Biodistribution, and Radiation Dosimetry of 68 Ga-OPS202 in Patients With Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Phase I Imaging Study

J Nucl Med. 2018 Jun;59(6):909-914. doi: 10.2967/jnumed.117.199737. Epub 2017 Oct 12.

Abstract

Preclinical and preliminary clinical evidence indicates that radiolabeled somatostatin (sst) receptor antagonists perform better than agonists in detecting neuroendocrine tumors (NETs). We performed a prospective phase I/II study to evaluate the sst receptor antagonist 68Ga-OPS202 (68Ga-NODAGA-JR11; NODAGA = 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid and JR11 = Cpa-c(dCys-Aph(Hor)-dAph(Cbm)-Lys-Thr-Cys)-dTyr-NH2)) for PET imaging. Here, we report the results of phase I of the study. Methods: Patients received 2 single 150-MBq intravenous injections of 68Ga-OPS202 3-4 wk apart (15 μg of peptide at visit 1 and 50 μg at visit 2). At visit 1, a dynamic PET/CT scan over the kidney was obtained during the first 30 min after injection, and static whole-body scans were obtained at 0.5, 1, 2, and 4 h after injection; at visit 2, a static whole-body scan was obtained at 1 h. Blood samples and urine were collected at regular intervals to determine 68Ga-OPS202 pharmacokinetics. Safety, biodistribution, radiation dosimetry, and the most appropriate imaging time point for 68Ga-OPS202 were assessed. Results: Twelve patients with well-differentiated gastroenteropancreatic (GEP) NETs took part in the study. 68Ga-OPS202 cleared rapidly from the blood, with a mean residence time of 2.4 ± 1.1 min/L. The organs with the highest mean dose coefficients were the urinary bladder wall, kidneys, and spleen. The calculated effective dose was 2.4E-02 ± 0.2E-02 mSv/MBq, corresponding to 3.6 mSv, for a reference activity of 150 MBq. Based on total numbers of detected malignant lesions, the optimal time window for the scan was between 1 and 2 h. For malignant liver lesions, the time point at which most patients had the highest mean tumor contrast was 1 h. 68Ga-OPS202 was well tolerated; adverse events were grade 1 or 2, and there were no signals of concern from laboratory blood or urinalysis tests. Conclusion:68Ga-OPS202 showed favorable biodistribution and imaging properties, with optimal tumor contrast between 1 and 2 h after injection. Dosimetry analysis revealed that the dose delivered by 68Ga-OPS202 to organs is similar to that delivered by other 68Ga-labeled sst analogs. Further evaluation of 68Ga-OPS202 for PET/CT imaging of NETs is therefore warranted.

Keywords: 68Ga-NODAGA-JR11; 68Ga-OPS202; dosimetry; neuroendocrine tumors; somatostatin receptor antagonist.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Acetates / adverse effects
  • Acetates / chemistry*
  • Acetates / pharmacokinetics*
  • Acetates / pharmacology
  • Female
  • Gallium Radioisotopes*
  • Heterocyclic Compounds, 1-Ring / adverse effects
  • Heterocyclic Compounds, 1-Ring / chemistry*
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics*
  • Heterocyclic Compounds, 1-Ring / pharmacology
  • Humans
  • Intestinal Neoplasms / diagnostic imaging*
  • Intestinal Neoplasms / metabolism
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / diagnostic imaging*
  • Neuroendocrine Tumors / metabolism
  • Oligopeptides / chemistry*
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pancreatic Neoplasms / metabolism
  • Positron-Emission Tomography / adverse effects
  • Positron-Emission Tomography / methods*
  • Radiometry
  • Receptors, Somatostatin / antagonists & inhibitors
  • Safety*
  • Stomach Neoplasms / diagnostic imaging*
  • Stomach Neoplasms / metabolism
  • Time Factors
  • Tissue Distribution

Substances

  • 1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane
  • Acetates
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Oligopeptides
  • Receptors, Somatostatin
  • Gallium-68

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor