title: Comparison of somatostatin receptor agonist and antagonist for peptide receptor radionuclide therapy: a pilot study.
abstract: Preclinical and clinical studies have indicated that somatostatin receptor (sst)-expressing tumors demonstrate higher uptake of radiolabeled sst antagonists than of sst agonists. In 4 consecutive patients with advanced neuroendocrine tumors, we evaluated whether treatment with (177)Lu-labeled sst antagonists is feasible.
  
  
  METHODS
  After injection of approximately 1 GBq of (177)Lu-DOTA-[Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr-NH2] ((177)Lu-DOTA-JR11) and (177)Lu-DOTATATE, 3-dimensional voxel dosimetry analysis based on SPECT/CT was performed. A higher tumor-to-organ dose ratio for (177)Lu-DOTA-JR11 than for (177)Lu-DOTATATE was the prerequisite for treatment with (177)Lu-DOTA-JR11.
  
  
  RESULTS
  Reversible minor adverse effects of (177)Lu-DOTA-JR11 were observed. (177)Lu-DOTA-JR11 showed a 1.7-10.6 times higher tumor dose than (177)Lu-DOTATATE. At the same time, the tumor-to-kidney and tumor-to-bone marrow dose ratio was 1.1-7.2 times higher. All 4 patients were treated with (177)Lu-DOTA-JR11, resulting in partial remission in 2 patients, stable disease in 1 patient, and mixed response in the other patient.
  
  
  CONCLUSIONS
  Treatment of neuroendocrine tumors with radiolabeled sst antagonists is clinically feasible and may have a significant impact on peptide receptor radionuclide therapy.
authors: Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany Division of Nuclear Medicine, University of Basel Hospital, Basel, Switzerland damian.wild@usb.ch.
authors: Damian
authors: D
authors: Wild
authors: Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany Division of Nuclear Medicine, University of Basel Hospital, Basel, Switzerland.
authors: Melpomeni
authors: M
authors: Fani
authors: Oncology "Dreiländereck," Lörrach, Germany.
authors: Richard
authors: R
authors: Fischer
authors: Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany.
authors: Luigi
authors: L
authors: Del Pozzo
authors: Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany Division of Nuclear Medicine, University of Basel Hospital, Basel, Switzerland.
authors: Felix
authors: F
authors: Kaul
authors: Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany.
authors: Simone
authors: S
authors: Krebs
authors: Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany.
authors: Richard
authors: R
authors: Fischer
authors: Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California.
authors: Jean E F
authors: JE
authors: Rivier
authors: Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Berne, Switzerland.
authors: Jean Claude
authors: JC
authors: Reubi
authors: Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany German Cancer Consortium (DKTK), Freiburg, Germany; and.
authors: Helmut R
authors: HR
authors: Maecke
authors: Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany German Cancer Consortium (DKTK), Freiburg, Germany; and Department of Radiology, Sloan-Kettering Cancer Center, New York, New York.
authors: Wolfgang A
authors: WA
authors: Weber
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008187:Lutetium / Q000627:therapeutic use; D008297:Male; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D009942:Organometallic Compounds / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D010865:Pilot Projects; D011868:Radioisotopes / Q000627:therapeutic use; D011874:Radiometry; D017481:Receptors, Somatostatin / Q000819:agonists* / Q000037:antagonists & inhibitors*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D009842:Oligopeptides; D009942:Organometallic Compounds; D011868:Radioisotopes; D017481:Receptors, Somatostatin; D008187:Lutetium; C447941:lutetium Lu 177 dotatate; D015282:Octreotide
keywords: antagonists; neuroendocrine tumors; somatostatin receptor targeting