Theranostic applications of antibodies in oncology

Abstract

Targeted therapies, including antibodies, are becoming increasingly important in cancer therapy. Important limitations, however, are that not every patient benefits from a specific antibody therapy and that responses could be short-lived due to acquired resistance. In addition, targeted therapies are quite expensive and are not completely devoid of side-effects. This urges the need for accurate patient selection and response monitoring. An important step towards personalizing antibody treatment could be the implementation of theranostics. Antibody theranostics combine the diagnostic and therapeutic potential of an antibody, thereby selecting those patients who are most likely to benefit from antibody treatment. This review focuses on the clinical application of theranostic antibodies in oncology. It provides detailed information concerning the suitability of antibodies for theranostics, the different types of theranostic tests available and summarizes the efficacy of theranostic antibodies used in current clinical practice. Advanced theranostic applications, including radiolabeled antibodies for non-invasive functional imagining, are also addressed. Finally, we discuss the importance of theranostics in the emerging field of personalized medicine and critically evaluate recent data to determine the best way to apply antibody theranostics in the future.

Keywords: Antibody; Biomarker; Molecular imaging; Personalized medicine; Theranostics.

Figure 1

Whole body biodistribution of a radiolabeled antibody. Whole‐body coronal PET/CT images of 124I‐girentuximab, acquired 5 days after antibody infusion. The specific uptake of the antibody can be seen in the left renal tumor (arrow), which is expressing the CAIX antigen. The concentration of the radiolabeled antibody in a tumor can be determined quantitatively. Left: CT, middle: PET, right: fused PET/CT. This figure was originally published in Nat Rev Cancer; reprinted with permission (Scott et al., 2012) (adapted).

Figure 2

Heterogeneous distribution of 124I‐girentuximab in RCC lesions. (A and B) Axial, sagittal, and coronal CT (top), PET (middle), and fused PET/CT (bottom) images of a patient with clear cell renal cancer with relatively homogeneous intratumoral distribution of the radiolabeled antibody (arrows) (A) and a patient with large, centrally necrotic clear cell renal cancer with marked heterogeneity (arrows) (B). (C) Axial CT (top), PET (middle), and fused PET/CT (bottom) images of a patient with advanced clear cell renal cancer. Antibody distribution within the primary tumor is heterogeneous (arrows), whereas distribution within metastatic nodes is relatively homogeneous (arrowheads). This figure was originally published in JNM; reprinted with permission (Pryma et al., 2011) (adapted).

Figure 3

111In‐bevacizumab imaging in a RCC patient before and after anti‐angiogenic treatment. Anterior and posterior 111In‐bevacizumab scans at baseline (A) and after 4 weeks of treatment with the TKI sorafenib (angiogenesis inhibitor; 400 mg twice daily) (B). A marked decrease of 111In‐bevacizumab uptake is observed (arrows). This figure was originally published in JNM; reprinted with permission (Desar et al., 2010) (adapted).

Figure 4

111In‐R1507 immuno‐SPECT and immunohistochemical IGF‐1R expression in mice with subcutaneous bone sarcoma xenografts. 111In‐R1507 immuno‐SPECT/CT scans (A) and IGF‐1R expression levels of corresponding tumors (B) in mice with bone sarcoma xenografts. Xenografts with high (OS‐1), intermediate (EW‐5), or no (EW‐8 and OS‐33) response to treatment with the IGF‐1R antibody R1507 were selected. Images were acquired 3 days post injection of 111In‐R1507. This figure was originally published in Clin Cancer Res; reprinted with permission (Fleuren et al., 2011) (adapted).