86Y based PET radiopharmaceuticals: radiochemistry and biological applications

Abstract

Development of targeted radionuclide therapy with (90)Y labeled antibodies and peptides has gained momentum in the past decade due to the successes of (90)Y-ibritumomab tiuxetan and (90)Y-DOTA-Phe(1)-Tyr(3)-octreotide in treatment of cancer. (90)Y is a pure β(-)-emitter and cannot be imaged for patient-specific dosimetry which is essential for pre-therapeutic treatment planning and accurate absorbed dose estimation in individual patients to mitigate radiation related risks. This review article describes the utility of (86)Y, a positron emitter (33%) with a 14.7-h half-life that can be imaged by positron emission tomography and used as an isotopically matched surrogate radionuclide for (90)Y radiation doses estimations. This review discusses various aspects involved in the development of (86)Y labeled radiopharmaceuticals with the specific emphasis on the radiochemistry and biological applications with antibodies and peptides.

Figure 1

Chemical structures of acyclic and macrocylic polyaminocarboxylates chelating agents used for radiolabeling with yttrium

Figure 2

Succinimidyl ester coupling chemistry for N-terminal conjugation of octreotide with N-hydroxysuccinimidyl penta-tert-butyl ester derivative of CHX-A″-DTPA with a glutaric acid spacer.

Figure 3

PET maximum intensity projections (3 d p.i.) of female athymic mouse bearing (A) subcutaneous LS-174T and (B) intraperitoneal LS-174T tumors injected with ⁸⁶Y-CHX-A″-DTPA-trastuzumab. (C) MRI of the female athymic mouse bearing intraperitoneal LS-174T tumors indicating the localization of the radiolabeled antibody in the tumor sites (C). White arrows indicate tumor sites. This figure is adapted from Milenic et al. [45].

Figure 4

Comparison of PET imaging of ⁸⁶Y labeled IgG, scFv, diabody and miniantibody construct of 19G9 in tumor bearing mice. Reprinted by permission of the Society of Nuclear Medine from Schneider at al. [48]