Radiation dosimetry of [131 I]ICF01012 in rabbits: Application to targeted radionuclide therapy for human melanoma treatment

Med Phys. 2018 Nov;45(11):5251-5262. doi: 10.1002/mp.13165. Epub 2018 Sep 24.

Abstract

Purpose: Dosimetry for melanoma-targeted radionuclide therapy (TRT) with [131 I]ICF01012, a melanin ligand, has been previously evaluated in mice bearing melanomas. In this study, activity distribution and dosimetry are performed on healthy rabbits (Fauve de Bourgogne) using SPECT-CT imaging and ex vivo measurements.

Material and methods: Ex vivo biodistribution (i.v. injection: 370 kBq/kg, n = 2 per point) is performed on blood, eyes, brain, lung, liver, kidneys, heart, stomach, and spleen. Dosimetry calculations follow the MIRD formalism: S values are calculated from CT images using the GATE Monte Carlo platform and activity distributions are obtained from SPECT-CT imaging (i.v. injection: 37 MBq/kg n = 3 per point). A specific study is presented to assess dose to human retina.

Results: Time-integrated activities based on SPECT-CT are in accordance with ex vivo measurements except for spleen. Doses to liver and eyes are the most significant, with respectively, 6.38 ± 0.50 Gy/GBq (evaluated through SPECT-CT imaging) and 45.8 ± 7.9 Gy/GBq (evaluated through ex vivo measurements). Characterization of ocular [131 I]ICF01012 biodistribution in rabbits and quantification of melanin allowed to assess a dose of 3.07 ± 0.70 Gy/GBq to human retina.

Conclusion: This study sustains [131 I]ICF01012 as a good candidate for melanoma TRT and open perspectives for personalized dosimetry calculation during phase I clinical transfer.

Keywords: GATE; dosimetry; imaging; pigmented melanoma; targeted radionuclide therapy.

MeSH terms

  • Animals
  • Female
  • Humans
  • Iodine Radioisotopes / therapeutic use*
  • Male
  • Melanoma / diagnostic imaging
  • Melanoma / metabolism
  • Melanoma / radiotherapy*
  • Quinoxalines / pharmacokinetics
  • Quinoxalines / therapeutic use*
  • Rabbits
  • Radiometry
  • Radiotherapy Dosage
  • Single Photon Emission Computed Tomography Computed Tomography
  • Software
  • Tissue Distribution
  • Tumor Protein, Translationally-Controlled 1

Substances

  • Iodine Radioisotopes
  • Iodine-131
  • N-(2-diethylaminoethyl)-6-iodoquinoxaline-2-carboxamide
  • Quinoxalines
  • Tpt1 protein, mouse
  • Tumor Protein, Translationally-Controlled 1