title: [(111)In-DTPA]octreotide tumor uptake in GEPNET liver metastases after intra-arterial administration: an overview of preclinical and clinical observations and implications for tumor radiation dose after peptide radionuclide therapy.
abstract: OBJECTIVE
  With the aim to improve peptide receptor radionuclide therapy effects in patients with gastroenteropancreatic neuroendocrine tumor (GEPNET) liver metastases we explored the effect of intra-arterial (IA) administration of [(111)In-DTPA]octreotide ((111)In-DTPAOC) on tumor uptake in an animal model and in a patient study.
  
  
  METHODS
  Preclinical study: After administering (111)In-DTPAOC intra-venously (IV) or IA, biodistribution studies were performed in rats with a hepatic somatostatin receptor subtype 2 (sst2)-positive tumor. Clinical study: 3 patients with neuroendocrine liver metastases were injected twice with (111)In-DTPAOC. The first injection was given IV, and 2 weeks later, the second was injected IA (hepatic artery). Planar images of the abdomen were made up to 72 hours after injection. Blood samples were taken and urine was collected. Pharmacokinetic modeling was performed on the IV and IA data of the same patient. Based on this model, additional (177)Lu dosimetry calculations for IV and IA administrations were performed.
  
  
  RESULTS
  The preclinical study showed a two-fold higher (111)In-DTPAOC tumor uptake after IA administration than after IV injection. Patient data showed a large variability in radioactivity increment in liver metastases after IA administration compared with IV administration. Renal radioactivity was not significantly lower after IA administration; (177)Lu dosimetry simulations in 1 patient using a maximum kidney radiation dose of 23 Gy showed IA administration resulted in a mean increase in tumor radiation dose of 2.9-fold.
  
  
  CONCLUSIONS
  Preclinical and clinical data both indicate that IA administration of radiolabeled somatostatin analogs via the hepatic artery can significantly increase radionuclide uptake in GEPNET, sst2-positive, liver metastases up to 72 hours postinjection, although the effect of IA administration can differ between patients.
authors.affiliation: 1 Department of Nuclear Medicine, Erasmus MC , Rotterdam, The Netherlands .
authors.forename: Stefan E
authors.initials: SE
authors.lastname: Pool
authors.forename: Boen L R
authors.initials: BL
authors.lastname: Kam
authors.forename: Gerben A
authors.initials: GA
authors.lastname: Koning
authors.forename: Mark
authors.initials: M
authors.lastname: Konijnenberg
authors.forename: Timo L M
authors.initials: TL
authors.lastname: Ten Hagen
authors.forename: Woulter A P
authors.initials: WA
authors.lastname: Breeman
authors.forename: Eric P
authors.initials: EP
authors.lastname: Krenning
authors.forename: Marion
authors.initials: M
authors.lastname: de Jong
authors.forename: Casper H J
authors.initials: CH
authors.lastname: van Eijck
mesh_terms: D000328:Adult; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000008:administration & dosage; D007261:Infusions, Intra-Arterial; D007414:Intestinal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000532:radiotherapy* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D015282:Octreotide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D004369:Pentetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D014018:Tissue Distribution
chemical_list: C497824:111In-octreotide, DTPA(0)-; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D004369:Pentetic Acid; D015282:Octreotide
keywords: intra-arterial injection; liver metastases; neuroendocrine tumor; radionuclide therapy; somatostatin