A method to improve quantitative radiotracing-based analysis of the in vivo biodistribution of drug carriers.

ABSTRACT: Biodistribution studies are essential in drug carrier design and translation, and radiotracing provides a sensitive quantitation for this purpose. Yet, for biodegradable formulations, small amounts of free-label signal may arise prior to or immediately after injection in animal models, causing potentially confounding biodistribution results. In this study, we refined a method to overcome this obstacle. First, we verified free signal generation in animal samples and then, mimicking it in a controllable setting, we injected mice intravenously with a radiolabeled drug carrier formulation (¹²⁵I-antibody/3DNA) containing a known amount of free radiolabel (¹²⁵I), or free ¹²⁵I alone as a control. Corrected biodistribution data were obtained by separating the free radiolabel from blood and organs postmortem, using trichloroacetic acid precipitation, and subtracting the confounding signal from each tissue measurement. Control free ¹²⁵I-radiolabel was detected at ≥85% accuracy in blood and tissues, validating the method. It biodistributed very heterogeneously among organs (0.6-39 %ID/g), indicating that any free ¹²⁵I generated in the body or present in an injected formulation cannot be simply corrected to the free-label fraction in the original preparation, but the free label must be empirically measured in each organ. Application of this method to the biodistribution of ¹²⁵I-antibody/3DNA, including formulations directed to endothelial target ICAM-1, showed accurate classification of free ¹²⁵I species in blood and tissues. In addition, this technique rendered data on the in vivo degradation of the traced agents over time. Thus, this is a valuable technique to obtain accurate measurements of biodistribution using ¹²⁵I and possibly other radiotracers.

SUBMITTER: Roki N 

PROVIDER: S-EPMC8126812 | biostudies-literature |

REPOSITORIES: biostudies-literature