Theranostics Using Antibodies and Antibody-Related Therapeutics

Abstract

In theranostics, radiolabeled compounds are used to determine a treatment strategy by combining therapeutics and diagnostics in the same agent. Monoclonal antibodies (mAbs) and antibody-related therapeutics represent a rapidly expanding group of cancer medicines. Theranostic approaches using these drugs in oncology are particularly interesting because antibodies are designed against specific targets on the tumor cell membrane and immune cells as well as targets in the tumor microenvironment. In addition, these drugs are relatively easy to radiolabel. Noninvasive molecular imaging techniques, such as SPECT and PET, provide information on the whole-body distribution of radiolabeled mAbs and antibodyrelated therapeutics. Molecular antibody imaging can potentially elucidate drug target expression, tracer uptake in the tumor, tumor saturation, and heterogeneity for these parameters within the tumor. These data can support drug development and may aid in patient stratification and monitoring of the treatment response. Selecting a radionuclide for theranostic purposes generally starts by matching the serum half-life of the mAb or antibody-related therapeutic and the physical half-life of the radionuclide. Furthermore, PET imaging allows better quantification than the SPECT technique. This information has increased interest in theranostics using PET radionuclides with a relatively long physical half-life, such as 89 Zr. In this review, we provide an overview of ongoing research on mAbs and antibodyrelated theranostics in preclinical and clinical oncologic settings. We identified 24 antibodies or antibody-related therapeutics labeled with PET radionuclides for theranostic purposes in patients. For this approach to become integrated in standard care, further standardization with respect to the procedures involved is required.

Antibody‐drug therapeutic conjugates: Potential of antibody‐siRNAs in cancer therapy

“…Positron emission tomography (PET) and optical imaging (OI) advancements have attracted researchers interest in the development of multimodal PET/OI probes that can be used for the diagnosis, and treatment of cancers (Moek KLG et al, 2017). In this manner, a conjugated antibody using copper-free click chemistry exhibited high selective tumor uptake (Zeglis et al, 2013).…”

Chemical aspects of metal ion chelation in the synthesis and application antibody‐based radiotracers

“…Over the last 2 decades, 89 Zr (t 1/2 = 78.41 h; β+ = 22.74%) has emerged as the most important radionuclide for immuno-PET. 4 Elsewhere in this issue of Journal of Labeled Compounds and Radiopharmaceuticals, Viola-Villegas and coworkers present a detailed overview of progress made in the use of 89 Zr-radiolabeled mAbs for clinical imaging. The following section focuses on the radiochemistry and coordination chemistry of 89 Zr 4+ ions.…”

“…ions (ionic radius = 0.85 Å) 21 induces significant bond polarization in the first coordination sphere, and the dative bonds have strong "covalent character." The very low solubility product of Zr(OH) 4 (log K sp = 56.94 ± 0.32) 39 means that Zr 4+ species have a strong tendency to hydrolyze and form colloidal species in aquo. Avoiding precipitation of Zr-oxo species requires the use of metal binding chelates that form exceptionally stable complexes with high-valent metal ions.…”

CD146‐Targeted Multimodal Image‐Guided Photoimmunotherapy of Melanoma

“…[8,9] Therefore, developing antibody-based diagnostic probes for melanoma is highly desirable and useful. In this setting, substantial preclinical and clinical studies strongly indicate that noninvasive PET imaging using radiolabeled antibodies (immu-noPET) has a valuable role in patient stratification and response assessment.…”