title: The tumour sink effect on the biodistribution of 68Ga-DOTA-octreotate: implications for peptide receptor radionuclide therapy.
abstract: OBJECTIVE
  Tumour sequestration of radiotracer may lead to decreased bioavailability in healthy tissue resulting in lower absorbed radiation dose to critical organs. This study aims to assess the impact of disease burden, body habitus and urinary excretion on the biodistribution of (68)Ga-DOTA-octreotate.
  
  
  METHODS
  Ten patients with highly varied burden of somatostatin receptor-positive neuroendocrine tumour on (68)Ga-DOTA-octreotate positron emission tomography (PET)/CT were selected. Volumes of interest were drawn to derive the average uptake of renal parenchyma, spleen and body background, as well as to compute the fraction of injected activity sequestered in tumour and excreted in urine. Uptake values were assessed for correlation with tumour sequestration, weight, lean body weight, body surface area and urinary excretion.
  
  
  RESULTS
  There was a trend for tumour sequestration, body habitus and urinary excretion to inversely influence all healthy tissue uptake values. In particular, renal uptake, splenic intensity and background soft tissue activity were all significantly correlated to composite factors combining tumour sequestration with body habitus and renal excretion. When combined with body habitus index or a body habitus index and renal excretion, tumour sequestration was strongly and significantly correlated inversely with renal uptake.
  
  
  CONCLUSIONS
  Our results suggest that tumour sequestration of (68)Ga-DOTA-octreotate is a major factor leading to a sink effect that decreases activity concentration in healthy organs such as the kidney. However, body habitus and renal function also influence tissue biodistribution, in a synergistic fashion. Compared with a fixed-dose peptide receptor radionuclide therapy protocol, an adjusted-dose regimen tailored to tumour burden, body habitus and renal function may allow greater radiation dose to individual lesions without substantially adding to toxicity in normal tissues.
authors.affiliation: Centre for Cancer Imaging, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Australia. Jean-Mathieu.Beauregard@chuq.qc.ca
authors.forename: Jean-Mathieu
authors.initials: JM
authors.lastname: Beauregard
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hofman
authors.forename: Grace
authors.initials: G
authors.lastname: Kong
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007267:Injections; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy*; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D017481:Receptors, Somatostatin / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: D009942:Organometallic Compounds; D017481:Receptors, Somatostatin; C513399:gallium Ga 68 dotatate