Zirconium-89 labeled antibodies: a new tool for molecular imaging in cancer patients

Abstract

Antibody based positron emission tomography (immuno-PET) imaging is of increasing importance to visualize and characterize tumor lesions. Additionally, it can be used to identify patients who may benefit from a particular therapy and monitor the therapy outcome. In recent years the field is focused on (89)Zr, a radiometal with near ideal physical and chemical properties for immuno-PET. In this review we will discuss the production of (89)Zr, the bioconjugation strategies, and applications in (pre-)clinical studies of (89)Zr-based immuno-PET in oncology. To date, (89)Zr-based PET imaging has been investigated in a wide variety of cancer-related targets. Moreover, clinical studies have shown the feasibility for (89)Zr-based immuno-PET to predict and monitor treatment, which could be used to tailor treatment for the individual patient. Further research should be directed towards the development of standardized and robust conjugation methods and improved chelators to minimize the amount of released Zr(4+) from the antibodies. Additionally, further validation of the imaging method is required. The ongoing development of new (89)Zr-labeled antibodies directed against novel tumor targets is expected to expand applications of (89)Zr-labeled immuno-PET to a valuable method in the medical imaging.

Figure 1

Schematic overview of ⁸⁹Zr-labeled antibody using DFO as chelator.

Figure 2

Specificity of ⁸⁹Zr-trastuzumab for HER2-positive tumors. Coronal ⁸⁹Zr-trastuzumab, ¹⁸F-FDG, and ¹⁸F-FLT PET images of athymic nude mice bearing subcutaneous HER2-positive NCI-N87 (left) and HER2-negative MKN-74 (right) are shown. ROIs (%ID/g) for ⁸⁹Zr-trastuzumab, ¹⁸F-FDG, and ¹⁸F-FLT are indicated. +ve = positive; −ve = negative. This research was originally published in [3]. © by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Figure 3

In vivo biodistribution experiments in nude mice bearing MIA PaCa-2 and A4 xenografts of radiolabeled anti-CD147 antibody 059-053. Samples were collected and weighted, and radioactivity was measured at days 1 (white bars), 2 (dot bars), 4 (gray bars), and 6 (black bars) after intravenous injection of 37 kBq each of ⁸⁹Zr-059-053 (a) and ¹²⁵I-059-053 (b). Data are expressed as mean ± SD (n = 5). *P < 0.01 versus ⁸⁹Zr-059-053 tumor uptake at each time point analyzed by ANOVA with the Student-Newman-Keuls method multiple comparison test. This research was originally published in [84].

Figure 4

Examples of ⁸⁹Zr-trastuzumab uptake 5 days after the injection: (a) a patient with liver and bone metastases and ((b) and (c)) two patients with multiple bone metastases. A number of lesions have been specifically indicated by arrows. This research was originally published in [101].

Figure 5

(a) Axial slices of ⁸⁹Zr-bevacizumab PET from patient with primary breast tumor (1) and lymph node metastasis (2). (b) Correlation between ⁸⁹Zr-bevacizumab tumor uptake (x-axis) and tumor VEGF-A (y-axis) levels as measured by ELISA (Pearson r = 0.49, P = 0.04). This research was originally published in [103]. © by the Society of Nuclear Medicine and Molecular Imaging, Inc.