PET radiometals for antibody labeling

Abstract

Recent advances in molecular characterization of tumors have made possible the emergence of new types of cancer therapies where traditional cytotoxic drugs and nonspecific chemotherapy can be complemented with targeted molecular therapies. One of the main revolutionary treatments is the use of monoclonal antibodies (mAbs) that selectively target the disseminated tumor cells while sparing normal tissues. mAbs and related therapeutics can be efficiently radiolabeled with a wide range of radionuclides to facilitate preclinical and clinical studies. Non-invasive molecular imaging techniques, such as Positron Emission Tomography (PET), using radiolabeled mAbs provide useful information on the whole-body distribution of the biomolecules, which may enable patient stratification, diagnosis, selection of targeted therapies, evaluation of treatment response, and prediction of dose limiting tissue and adverse effects. In addition, when mAbs are labeled with therapeutic radionuclides, the combination of immunological and radiobiological cytotoxicity may result in enhanced treatment efficacy. The pharmacokinetic profile of antibodies demands the use of long half-life isotopes for longitudinal scrutiny of mAb biodistribution and precludes the use of well-stablished short half-life isotopes. Herein, we review the most promising PET radiometals with chemical and physical characteristics that make the appealing for mAb labeling, highlighting those with theranostic radioisotopes.

Keywords: ImmunoPET; isotope production; radiolabelling; radiometals; theranostic.

FIGURE 1

A, Simplified decay scheme of ⁸⁹Zr (data taken from the National Nuclear Data Center: www.nndc.bnl.gov), B, schematic overview of ⁸⁹Zr-labeled antibody using DFO as chelator, and C, biodistribution of ⁸⁹Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer (reprinted with permission from Dijkers EC, et al Clinical Pharmacology & Therapeutics 2010; 87: 586–592)

FIGURE 2

A, Simplified decay scheme of ⁶⁴Cu (data taken from the National Nuclear Data Center: www.nndc.bnl.gov), B, schematic overview of ⁶⁴Cu-labeled antibody using DOTA as chelator, and C, ⁶⁴Cu-DOTA-trastuzumab PET images of HER2-positive metastatic brain lesions (arrows) (This research was originally published in JNM. Tamura K et al. 64Cu-DOTA-Trastuzumab PET Imaging in Patients with HER2-Positive Breast Cancer. J Nucl Med 2013; 54:1869–1875. © by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

FIGURE 3

Simplified decay scheme of ⁸⁶Y (data taken from the National Nuclear Data Center: www.nndc.bnl.gov)

FIGURE 4

Simplified decay scheme of ⁵²Mn (data taken from the National Nuclear Data Center: www.nndc.bnl.gov)

FIGURE 5

Simplified decay scheme of ⁵⁵Co (data taken from the National Nuclear Data Center: www.nndc.bnl.gov)

FIGURE 6

Simplified decay scheme of ¹⁵²Tb (data taken from the National Nuclear Data Center: www.nndc.bnl.gov)

FIGURE 7

Simplified decay scheme of ⁹⁰Nb (data taken from the National Nuclear Data Center: www.nndc.bnl.gov)

FIGURE 8

Simplified decay scheme of ⁶⁶Ga (data taken from the National Nuclear Data Center: www.nndc.bnl.gov)

FIGURE 9

Simplified decay scheme of ⁷²As (data taken from the National Nuclear Data Center: www.nndc.bnl.gov)

FIGURE 10

Simplified decay scheme of ⁶⁹Ge (data taken from the National Nuclear Data Center: www.nndc.bnl.gov)