title: Comparison of 111In-[DTPA0]Octreotide Versus Non Carrier Added 177Lu- [DOTA0,Tyr3]-Octreotate Efficacy in Patients With GEP-NET Treated Intra-arterially for Liver Metastases.
abstract: OBJECTIVE
  In patients with progressive, metastatic neuroendocrine tumors (NET), intra-arterial radionuclide infusions with high activities of In-[DTPA]-octreotide and more recently with non-carrier added (nca) Lu-[DOTA,Tyr]-octreotate have been performed with encouraging results. However, the affinity profiles (IC50) of these radiopeptides for human sst2 receptors are markedly different (In-[DTPA]-octreotide, 22 ± 3.6 nM and nca Lu-[DOTA,Tyr]-octreotate, 1.5 ± 4.0 nM). The total administered activity is determined by organ dose limits (kidneys and bone marrow), and our aim therefore was to compare and evaluate the therapeutic efficacy of both radiopeptides in metastatic NETs.
  
  
  METHODS
  Thirty patients with gastroenteropancreatic (GEP) somatostatin-positive NETs with liver metastases confirmed on biopsy and In-pentetreotide scan were included. They were treated with In-[DTPA]-octreotide (n = 17) or nca Lu-[DOTA,Tyr]-octreotate (n = 13). Blood samples were collected 2, 4, 8, and 24 hours postadministration to calculate residence time in blood and in red marrow. The maximum percentage uptake in organs and tumors was estimated by region of interest analysis, and tumor dosimetry calculations were performed using OLINDA/EXM/ 1.0 software.
  
  
  RESULTS
  ncaLu-[DOTA,Tyr3]-octreotate blood radioactivity, expressed as a percentage of the injected dose, was significantly lower than In-[DTPA]-octreotide (P < 0.05), as clearly depicted from the time-activity curves; the background-corrected tumor uptake was significantly higher than In-[DTPA]-octreotide but without any significant difference in other organs (spleen, kidneys, and liver).
  
  
  CONCLUSIONS
  Using Lu-[DOTA,Tyr]-octreotate, a 3-fold higher absorbed dose to tumor tissue was achieved compared with In-[DTPA] octreotide. Residence time of nca Lu-[DOTA,Tyr]-octreotate results in a significantly higher absorbed dose to bone marrow compared with In-[DTPA]-octreotide. However, a drawback of In-[DTPA]-octreotide therapy is that the number of administrations would need to be almost doubled to achieve an equal therapeutic outcome as compared with Lu-[DOTA,Tyr]-octreotate.
authors.affiliation: From the *Division of Nuclear Medicine-I Radiology Department, "Aretaieion" Hospital, Athens University Medical Faculty, Greece; †Department of Nuclear Medicine, Santa Maria della Misericordia Hospital, Rovigo, Italy; ‡Neurologic Clinic 'Aeginiteion' Hospital, Athens University Medical Faculty, Greece; Departments of §Pathology, and ∥II Surgery, Athens University Medical Faculty, Greece; ¶Department of Nuclear Medicine, Royal Sussex County Hosp, Brighton, UK; **Department of Radiology, University of Southern California, Los Angeles, CA; and ††Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London, UK.
authors.forename: G S
authors.initials: GS
authors.lastname: Limouris
authors.forename: V
authors.initials: V
authors.lastname: Poulantzas
authors.forename: N
authors.initials: N
authors.lastname: Trompoukis
authors.forename: I
authors.initials: I
authors.lastname: Karfis
authors.forename: S
authors.initials: S
authors.lastname: Chondrogiannis
authors.forename: N
authors.initials: N
authors.lastname: Triantafyllou
authors.forename: V
authors.initials: V
authors.lastname: Gennimata
authors.forename: L-E
authors.initials: LE
authors.lastname: Moulopoulou
authors.forename: E
authors.initials: E
authors.lastname: Patsouris
authors.forename: G
authors.initials: G
authors.lastname: Nikou
authors.forename: V
authors.initials: V
authors.lastname: Michalaki
authors.forename: G
authors.initials: G
authors.lastname: Fragulidis
authors.forename: M
authors.initials: M
authors.lastname: Paphiti
authors.forename: R V
authors.initials: RV
authors.lastname: McCready
authors.forename: P M
authors.initials: PM
authors.lastname: Colletti
authors.forename: G J
authors.initials: GJ
authors.lastname: Cook
authors.forename: D
authors.initials: D
authors.lastname: Rubello
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000532:radiotherapy* / Q000556:secondary; D008297:Male; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004369:Pentetic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: C497824:111In-octreotide, DTPA(0)-; C504257:177Lu-octreotide, DOTA(0)-Tyr(3)-; D019275:Radiopharmaceuticals; D004369:Pentetic Acid; D015282:Octreotide