Mid-way seminar: Peptide receptor radionuclide therapy with 177Lu-DOTATATE in small-intestinal and pancreatic neuroendocrine neoplasms; Aspects of tumor characteristics and receptor recycling

  • Date:
  • Lecturer: Doctoral student: Ulrika Jahn
  • Contact person: Anders Sundin (huvudhandledare)
  • Halvtidsseminarium

The seminar will be held in Swedish.

A zoom-link will soon be here.
 

Abstract

Background: Well-differentiated neuroendocrine neoplasms (NENs) are characterized by an abundance of somatostatin receptors (SSTR) that can be targeted with somatostatin analogs (SSA). When activated with a single dose of SSA, the receptor-ligand complex is internalized and the receptor is by default recycled within 24 h. Ongoing medication with long-acting SSAs at 111Inpentetreotide-scintigraphy and 68Ga-DOTA-SSA-PET have been shown to increase the tumor-tonormal organ contrast. This study was performed to investigate the time dependent extended effect (7h) of a single intravenous dose of 400 µg short-acting octreotide on the tumor versus normal tissue uptake of 68Ga-DOTATOC.

Methods: Patients with small-intestinal NETs received a single intravenous dose of 400 µg octreotide and underwent dynamic abdominal 68Ga-DOTATOC-PET/CT at three sessions (0, 3 and 6 h) plus static whole-body (WB) PET/CT (1, 4 and 7 h), starting each PET/CT session by administering 167±21 MBq, 23.5±4.2 µg (mean±SD, n=12) of 68Ga-DOTATOC. A previously acquired clinical whole-body 68Ga-DOTATOC scan was used as baseline. SUV and net uptake rate Ki were calculated in tumors and healthy organs during each imaging session, after correction for remaining activity from previous scans.

Results: Tumor SUV decreased significantly compared to baseline at 1 and 4 h post injection but subsequently increased over time and was no longer significantly lower than baseline at 7 h, whereas SUV in liver, spleen and pancreas remained significantly below baseline also at 7 h. The tumor net uptake rate Ki similarly showed a significant increase over time between the first and third examination. Hence, the receptor turn-over in tumors exceeded that in the normal tissue, liver, spleen and pancreas, and the restitution of tumor 68Ga-DOTATOC uptake was mainly completed at 7 hours. This was corroborated by the linear correlation between tumor SUV and Ki.

Conclusion: SSTR recycling is faster in small-intestinal NETs than in normal organs - liver, spleen and pancreas. This opens the possibility to protect normal tissues during PRRT by administering a 3 single dose of cold peptide hours before peptide receptor radionuclide therapy (PRRT), and most likely additionally improve the availability and uptake of the therapeutic preparation in the tumors.

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