Molecular Imaging and Biology

, Volume 13, Issue 2, pp 215–221

Biodistribution and Clearance of Small Molecule Hapten Chelates for Pretargeted Radioimmunotherapy

  • Kelly Davis Orcutt
  • Khaled A. Nasr
  • David G. Whitehead
  • John V. Frangioni
  • K. Dane Wittrup
Brief Article

DOI: 10.1007/s11307-010-0353-6

Cite this article as:
Orcutt, K.D., Nasr, K.A., Whitehead, D.G. et al. Mol Imaging Biol (2011) 13: 215. doi:10.1007/s11307-010-0353-6

Abstract

Purpose

The favorable pharmacokinetics and clinical safety profile of metal-chelated 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) suggests that it might be an ideal hapten for pretargeted radioimmunotherapy. In an effort to minimize hapten retention in normal tissues and determine the effect of various chemical adducts on in vivo properties, a series of DOTA-based derivatives were evaluated.

Procedures

Biodistribution and whole-body clearance were evaluated for 177Lu-labeled DOTA, DOTA-biotin, a di-DOTA peptide, and DOTA-aminobenzene in normal CD1 mice. Kidney, liver, and bone marrow doses were estimated using standard Medical Internal Radiation Dose methodology.

Results

All haptens demonstrated similar low tissue and whole-body retention, with 2–4% of the injected dose remaining in mice 4 h postinjection. The kidney is predicted to be dose limiting for all 177Lu-labeled haptens tested with an estimated kidney dose of approximately 0.1 mGy/MBq.

Conclusions

We present here a group of DOTA-based haptens that exhibit rapid clearance and exceptionally low whole-body retention 4 h postinjection. Aminobenzene, tyrosine–lysine, and biotin groups have minimal effects on the blood clearance and biodistribution of 177Lu-DOTA.

Key words

Pretargeted radioimmunotherapyDOTABiodistributionClearanceRadiation dosimetry

Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2010

Authors and Affiliations

  • Kelly Davis Orcutt
    • 1
  • Khaled A. Nasr
    • 4
  • David G. Whitehead
    • 4
  • John V. Frangioni
    • 4
    • 5
  • K. Dane Wittrup
    • 1
    • 2
    • 3
  1. 1.Department of Chemical EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.Department of Biological EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  3. 3.Koch Institute for Integrative Cancer ResearchMassachusetts Institute of TechnologyCambridgeUSA
  4. 4.Division of Hematology/OncologyBeth Israel Deaconess Medical CenterBostonUSA
  5. 5.Department of MedicineBeth Israel Deaconess Medical CenterBostonUSA