title: Experimental facts supporting a red marrow uptake due to radiometal transchelation in 90Y-DOTATOC therapy and relationship to the decrease of platelet counts.
abstract: OBJECTIVE
  The aim of this study was to retrospectively evaluate whether the red marrow (RM) takes up (111)In-diethylenetriaminepentaacetic acid (DTPA)-D-Phe(1)-octreotide and (86)Y-DOTATOC and to assess the correlation between the RM absorbed doses and platelet count reduction as a biological dose estimate.
  
  
  METHODS
  Data from 12 patients who underwent at 24 h p.i. high statistics (111)In single photon emission computed tomography (SPECT) and (86)Y positron emission tomography (PET) acquisitions of the chest were analysed. Uptake was measured on >7 cm spine length and converted to total RM uptake using standard RM distribution in man. RM absorbed doses were calculated assuming specific RM uptake and using the plasma and remainder of the body models. RM doses were correlated with the platelet count reduction at 4 weeks. In vitro experiments explored the metabolism of (111)In-DTPA-D-Phe(1)-octreotide and (90)Y-DOTATOC in plasma.
  
  
  RESULTS
  The correlation between the uptake of both tracers was excellent (R = 0.80), indicating that RM uptake of (86)Y-DOTATOC reflects a real physiological process and not reconstruction artefacts. The kinetics of (86)Y-DOTATOC RM activity was different than that in blood and tumours, with no activity at 4 h p.i. indicating that the uptake is not somatostatin receptor dependent. In vitro experiments showed a transchelation of both radiometals to free transferrin that could explain the RM uptake. In patients without chemotherapy and with a normal platelet count recovery, a good correlation (R = 0.96) was found between the RM doses and the platelet count reduction at the nadir.
  
  
  CONCLUSIONS
  These experimental facts support the existence of a true RM uptake likely related to transchelation of the radiometal to transferrin. RM uptake correlates well with the observed acute RM toxicity.
authors.affiliation: Centre de Médecine Nucléaire, Université Catholique de Louvain, Avenue Hippocrate 10, 1200 Brussels, Belgium. stephan.walrand@uclouvain.be
authors.forename: Stephan
authors.initials: S
authors.lastname: Walrand
authors.forename: Raffaella
authors.initials: R
authors.lastname: Barone
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pauwels
authors.forename: François
authors.initials: F
authors.lastname: Jamar
mesh_terms: D000328:Adult; D000368:Aged; D001692:Biological Transport; D001792:Blood Platelets / Q000166:cytology / Q000528:radiation effects*; D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000528:radiation effects*; D002614:Chelating Agents / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D004369:Pentetic Acid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D010976:Platelet Count; D049268:Positron-Emission Tomography; D011829:Radiation Dosage; D011859:Radiography; D012189:Retrospective Studies; D015899:Tomography, Emission-Computed, Single-Photon; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D002614:Chelating Agents; C071632:SDZ 215-811; D004369:Pentetic Acid; C496730:90Y-octreotide, DOTA-Tyr(3)-; D015282:Octreotide