title: Hepatic arterial infusion enhances DOTATOC radiopeptide therapy in patients with neuroendocrine liver metastases.
abstract: Intravenously administered radiolabeled peptides targeting somatostatin receptors are used for the treatment of unresectable gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Recently, we demonstrated a high first-pass effect during intra-arterial (i.a.) administration of positron emission tomography (PET) labeled (68)Ga-DOTA(0)-d-Phe(1)-Tyr(3)-octreotide (DOTATOC). In this pilot study, we investigated the therapeutic effectiveness of arterial administered DOTATOC, labeled with the therapeutic β emitters (90)Y and (177)Lu. (90)Y- and/or (177)Lu-DOTATOC were infused into the hepatic artery of 15 patients with liver metastases arising from GEP-NETs. Response was assessed using DOTATOC-PET, multiphase contrast enhanced computed tomography, magnetic resonance imaging, and the serum tumor marker chromogranin A. Pharmacokinetic data of the arterial approach were assessed using (111)In-DOTATOC scans. With the treatment regime of this pilot study, complete remission was achieved in one (7%) patient and partial remission was observed in eight (53%) patients, six patients were classified as stable (40%; response evaluation criteria in solid tumors criteria). The concomitant decrease of elevated serum tumor marker confirmed the radiologic response. Median time to progression was not reached within a mean follow-up period of 20 months. Receptor saturation and redistribution effects were identified as limiting factors for i.a. DOTATOC therapy. The high rate of objective radiologic response in NET patients treated with arterial infusion of (90)Y-/(177)Lu-DOTATOC compares favorably with systemic chemotherapy and intravenous radiopeptide therapy. While i.a. DOTATOC therapy is only applicable to patients with tumors of limited anatomic distribution, the results of this pilot study are a promising development in the treatment of GEP-NET and warrants further investigation of this novel approach.
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120 Heidelberg, Germany. clemens.kratochwil@med.uni-heidelberg.de
authors.forename: Clemens
authors.initials: C
authors.lastname: Kratochwil
authors.forename: Ruben
authors.initials: R
authors.lastname: López-Benítez
authors.forename: Walter
authors.initials: W
authors.lastname: Mier
authors.forename: Sabine
authors.initials: S
authors.lastname: Haufe
authors.forename: Berend
authors.initials: B
authors.lastname: Isermann
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Kauczor
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
authors.forename: Frederik L
authors.initials: FL
authors.lastname: Giesel
mesh_terms: D000328:Adult; D000368:Aged; D053379:Chromogranin A / Q000097:blood; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary; D015282:Octreotide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed; D015021:Yttrium Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D053379:Chromogranin A; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D015282:Octreotide; C106246:Edotreotide