title: Individualized dosimetry-based activity reduction of ⁹⁰Y-DOTATOC prevents severe and rapid kidney function deterioration from peptide receptor radionuclide therapy.
abstract: OBJECTIVE
  Assessment of kidney function evolution after (90)Y-DOTATOC peptide receptor radionuclide therapy (PRRT) with capped activity administration based on a 37-Gy threshold of biological effective dose (BED) to the kidney.
  
  
  METHODS
  In a prospective phase II study, patients with metastasized neuroendocrine tumours were evaluated for therapy using 185 MBq (111)In-pentetreotide with amino acid coinfusion. Planar whole-body images were acquired at four time-points after injection and kidney volumes were measured using CT/MRI. BED to the kidneys was estimated using an extended BED formula and biexponential renal clearance. Based on published BED dose-toxicity relationships, we allowed a maximal kidney BED of 37 Gy; if the calculated BED exceeded 37 Gy, treatment activity was reduced accordingly. Kidney function was assessed at baseline and at 18 months, predominantly using (51)Cr-EDTA. The rate of renal function decline was expressed as annual glomerular filtration rate loss (aGFRL).
  
  
  RESULTS
  Only 22 of 50 patients reached the 18-months time-point, with most missing patients having died due to disease progression. In the 22 patients who reached 18 months, no rapid kidney function deterioration was observed over the 18 months, aGFRL >33% was not seen, and only three patients showed an increase of one toxicity grade and one patient an increase of two grades. No significant correlations between kidney volume (p = 0.35), baseline GFR (p = 0.18), risk factors for renal function loss (p = 0.74) and aGFRL were observed. Among the 28 patients who did not reach 18 months, one developed grade 4 kidney toxicity at 15 months after PRRT.
  
  
  CONCLUSIONS
  Prospective dosimetry using a 37 Gy BED as the threshold for kidney toxicity is a good guide for (90)Y-DOTATOC PRRT and is associated with a low risk of rapid renal function deterioration and evolution to severe nephrotoxicity.
authors.affiliation: Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium, sofie.vanbinnebeek@uzleuven.be.
authors.forename: Sofie
authors.initials: S
authors.lastname: Van Binnebeek
authors.forename: Kristof
authors.initials: K
authors.lastname: Baete
authors.forename: Bert
authors.initials: B
authors.lastname: Vanbilloen
authors.forename: Christelle
authors.initials: C
authors.lastname: Terwinghe
authors.forename: Michel
authors.initials: M
authors.lastname: Koole
authors.forename: Felix M
authors.initials: FM
authors.lastname: Mottaghy
authors.forename: Paul M
authors.initials: PM
authors.lastname: Clement
authors.forename: Luc
authors.initials: L
authors.lastname: Mortelmans
authors.forename: Karin
authors.initials: K
authors.lastname: Haustermans
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: Alfons
authors.initials: A
authors.lastname: Verbruggen
authors.forename: Kris
authors.initials: K
authors.lastname: Bogaerts
authors.forename: Chris
authors.initials: C
authors.lastname: Verslype
authors.forename: Christophe M
authors.initials: CM
authors.lastname: Deroose
mesh_terms: D000328:Adult; D000368:Aged; D004067:Digestive System Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology / Q000528:radiation effects; D007677:Kidney Function Tests; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D057285:Precision Medicine / Q000379:methods; D011829:Radiation Dosage; D011874:Radiometry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D015282:Octreotide; C106246:Edotreotide