Does the Number of Bifunctional Chelators Conjugated to a mAb Affect the Biological Activity of Its Radio-Labeled Counterpart? Discussion Using the Example of mAb against CD-20 Labeled with 90Y or 177Lu

Abstract

There has been considerable interest in developing a monoclonal antibody (mAb) against-CD-20 (for example, Rituximab) modified by bifunctional chelating agents (BCA) for non-Hodgkin's lymphoma radioimmunotherapy. Therefore, many researchers have modified this monoclonal antibody by attaching different BCA moieties and evaluated their biological activities in terms of in vitro study and in vivo study in healthy and tumor xenografted rodents. This mini-perspective reviews the in vitro studies, the immunoreactivity and physiological distribution studies: organ-to-blood and the tumor-to-organ ratio of conjugates with different numbers of chelators per mAb. We set up a null hypothesis that states there is no statistical significance between the biological activity of monoclonal antibody (Rituximab) and the number of conjugated bifunctional chelators. Overall, we have concluded that there is no strong evidence for this hypothesis. However, the literature data should be questioned due to the potential lack of uniform study methodology.

Figure 1

Quantity of calculated DOTA chelators per mAb-based on the initial amount of DOTA and different analytical methods, based on data listed in Table 1. Linear correlation (R² = 0.8775) refers to data calculated using the spectrophotometric method (▲). The correlation does not consider the marked as (▼, spectrophotometric method), (⧫, HPLC method), and (●, MALDI SM method).

Figure 2

Scatterplot of IRF and number of initial (A) and detected (B) DOTA molecules to Rituximab, based on data listed in Table 1. There are two correlation lines in part (A): first is for DOTA: mAb ratio range from 0 to 25 (red line R²_0–25), and second is for DOTA:mAb ratio range from 0 to 100 (black line R²_0–100).

Figure 3

Graphical presentation of target-to-blood (A) and tumor-to-target ratios (B) for conjugates with different numbers of chelators conjugated to Rituximab. Data was collected 24 h after intravenous administration—analyses based on data listed in Tables 3 and 4, respectively.