In vivo binding of [68Ga]-DOTATOC to somatostatin receptors in neuroendocrine tumours--impact of peptide mass

Nucl Med Biol. 2010 Apr;37(3):265-75. doi: 10.1016/j.nucmedbio.2009.11.008. Epub 2010 Jan 15.

Abstract

Objectives: The aim of this pilot study was to explore the impact of peptide mass on binding of [(68)Ga]-DOTATOC to neuroendocrine tumour somatostatin receptors in vivo using a tracer of variable specific radioactivity (SRA) and to show the logistic feasibility of sequential PET scans in the same patient.

Material and methods: Nine patients with gastroenteropancreatic neuroendocrine tumours were included. Six of them underwent three sequential PET-CT examinations with intravenous injections of [(68)Ga]-DOTATOC proceeded by 0, 50 and 250 or 500 microg of octreotide, administered 10 min before the tracer. Three patients were examined by dynamic and static PET/CT for pharmacokinetic and dosimetric calculations. The [(68)Ga]-DOTATOC synthesis included preconcentration and purification of the generator eluate and microwave heating in a semi-automated in-house procedure.

Results: [(68)Ga]-DOTATOC synthesis and quality control were accomplished within 30 min and radiochemical purity was >95%. The tracer accumulation in the tumours varied and depended on the total amount of the administered peptide. In five of six patients, the highest tumour-to-normal tissue ratio was found when 50 microg of octreotide was preadministered. One patient showed a continuously increasing tumour uptake. Dosimetrically, a large variation in organ doses was found (kidney: 0.086-0.168 mSv/MBq; liver: 0.026-0.096 mSv/MBq; spleen: 0.046-0.226 mSv/MBq). The effective dose (0.015, 0.0067 and 0.0042 mSv/MBq) was correlated to the total amount of decays.

Discussion: Three sequential PET-CT examinations using (68)Ga-based tracer was carried out in 1 day. The use of high SRA [(68)Ga]-DOTATOC and unlabelled octreotide indicates an optimal mass leading to better image contrast. [(68)Ga]-DOTATOC-PET-CT employing variable SRA may be utilised for accurate quantification of tumour uptake with subsequent dosimetry for personalized therapy management.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / diagnostic imaging*
  • Neuroendocrine Tumors / metabolism*
  • Octreotide / analogs & derivatives*
  • Octreotide / pharmacokinetics
  • Organometallic Compounds / pharmacokinetics*
  • Pilot Projects
  • Protein Binding
  • Radionuclide Imaging
  • Radiopharmaceuticals / pharmacokinetics
  • Receptors, Somatostatin / metabolism*

Substances

  • Ga(III)-DOTATOC
  • Organometallic Compounds
  • Radiopharmaceuticals
  • Receptors, Somatostatin
  • Octreotide