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Individualized dosimetry-based activity reduction of 90Y-DOTATOC prevents severe and rapid kidney function deterioration from peptide receptor radionuclide therapy

  • Sofie Van Binnebeek
  • Kristof Baete
  • Bert Vanbilloen
  • Christelle Terwinghe
  • Michel Koole
  • Felix M. Mottaghy
  • Paul M. Clement
  • Luc Mortelmans
  • Karin Haustermans
  • Eric Van Cutsem
  • Alfons Verbruggen
  • Kris Bogaerts
  • Chris Verslype
  • Christophe M. Deroose
Original Article

Abstract

Purpose

Assessment of kidney function evolution after 90Y-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 111In-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 51Cr-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.

Conclusion

Prospective dosimetry using a 37 Gy BED as the threshold for kidney toxicity is a good guide for 90Y-DOTATOC PRRT and is associated with a low risk of rapid renal function deterioration and evolution to severe nephrotoxicity.

Keywords

PRRT Dosimetry Renal function 90Y-DOTATOC 

Notes

Acknowledgments

The project was funded by Instituut voor de Aanmoediging van Innovatie door Wetenschap en Technologie in Vlaanderen (IWT) (http://www.iwt.be) with grant “Innovatie door Wetenschap en Technologie-Toegepast Biomedisch onderzoek met een primair Maatschappelijke finaliteit project no. 0707181”. S.V.B. is a beneficiary of an Emmanuel van der Schueren grant of the Vlaamse Liga tegen Kanker. C.M.D. is a postdoctoral fellow of the Clinical Research Fund of the UZ Leuven. This study was partially funded within the framework of ORAMED for which funding was received from the European Community’s Seventh Framework Program (FP7/2007/2011) under grant agreement no. 211361.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

259_2013_2670_MOESM1_ESM.docx (196 kb)
ESM 1 (DOCX 195 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Sofie Van Binnebeek
    • 1
    • 2
  • Kristof Baete
    • 1
    • 2
  • Bert Vanbilloen
    • 1
    • 2
  • Christelle Terwinghe
    • 1
    • 2
  • Michel Koole
    • 3
  • Felix M. Mottaghy
    • 4
    • 5
  • Paul M. Clement
    • 6
    • 7
  • Luc Mortelmans
    • 1
    • 2
  • Karin Haustermans
    • 8
    • 9
  • Eric Van Cutsem
    • 9
    • 10
  • Alfons Verbruggen
    • 11
  • Kris Bogaerts
    • 12
  • Chris Verslype
    • 9
    • 10
  • Christophe M. Deroose
    • 1
    • 2
    • 13
  1. 1.Nuclear MedicineUniversity Hospitals LeuvenLeuvenBelgium
  2. 2.Department of Imaging & PathologyKU LeuvenLeuvenBelgium
  3. 3.Department of Nuclear MedicineUniversity Medical Centre GroningenGroningenThe Netherlands
  4. 4.Department of Nuclear MedicineUniversity Hospital AachenAachenGermany
  5. 5.Department of Nuclear MedicineMaastricht University Medical CenterMaastrichtThe Netherlands
  6. 6.Medical OncologyUniversity Hospitals LeuvenLeuvenBelgium
  7. 7.Laboratory of Experimental OncologyKU LeuvenLeuvenBelgium
  8. 8.Radiation OncologyUniversity Hospitals LeuvenLeuvenBelgium
  9. 9.Department of OncologyKU LeuvenLeuvenBelgium
  10. 10.Division of Digestive OncologyUniversity Hospitals LeuvenLeuvenBelgium
  11. 11.Laboratory for RadiopharmacyKU LeuvenLeuvenBelgium
  12. 12.Division of Public Health and Primary Care (I-Biostat)KU LeuvenLeuvenBelgium
  13. 13.Nuclear MedicineUZ LeuvenLeuvenBelgium

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