177 Lu-3BP-227 for Neurotensin Receptor 1-Targeted Therapy of Metastatic Pancreatic Adenocarcinoma: First Clinical Results

J Nucl Med. 2018 May;59(5):809-814. doi: 10.2967/jnumed.117.193847. Epub 2017 Oct 12.

Abstract

Neurotensin receptor 1 (NTR1) is overexpressed in ductal pancreatic adenocarcinoma, which is still one of the deadliest cancers, with a very poor prognosis. Eligible patients were offered salvage radiopharmaceutical therapy with the novel NTR1 antagonist 177Lu-3BP-227. Methods: Six patients with confirmed ductal pancreatic adenocarcinoma who had exhausted all other treatment options received 177Lu-3BP-227 for evaluation of NTR1 expression in vivo. Three patients received treatment activities of 5.1-7.5 GBq. Results: Administration of 177Lu-3BP-227 was well tolerated by all patients. The kidneys were identified as the dose-limiting organ. The most severe adverse event was reversible grade 2 anemia. One patient achieved a partial response and experienced significant improvement of symptoms and quality of life. This patient survived 13 mo from diagnosis and 11 mo from the start of 177Lu-3BP-227 therapy. Conclusion: This initial report provides clinical evidence of the feasibility of treatment of ductal pancreatic adenocarcinoma using 177Lu-3BP-227.

Keywords: 177Lu; TRLT; dosimetry; neurotensin receptor 1 antagonist; pancreatic adenocarcinoma; targeted radioligand therapy.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / therapy*
  • Aged
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / therapy*
  • Combined Modality Therapy
  • Drug Design
  • Female
  • Humans
  • Injections, Intravenous
  • Kidney / radiation effects
  • Lutetium / pharmacology*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / therapy*
  • Quality of Life
  • Radiometry
  • Radionuclide Imaging
  • Radiopharmaceuticals
  • Receptors, Neurotensin / antagonists & inhibitors*
  • Retrospective Studies
  • Salvage Therapy
  • Tomography, Emission-Computed, Single-Photon
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Radiopharmaceuticals
  • Receptors, Neurotensin
  • neurotensin type 1 receptor
  • Lutetium