Evaluation of carbon-14-colchicine biodistribution with whole-body quantitative autoradiography in colchicine-sensitive and -resistant xenografts.

Overview

UNLABELLED: Quantitative autoradiography (QAR) with radiolabeled monoclonal antibodies in xenografted animals has been extensively described in the past, either on individual tissues or on the whole body. We applied whole-body QAR to identify multidrug resistant tumors using 14C-colchicine (14C-CHC). METHODS: Two groups of five animals each were xenografted with CHC-sensitive and CHC-resistant human neuroblastoma cells. Animals were injected intravenously with 4 microCi/0.11 mumole 14C-CHC per gram of body weight and sacrificed after 60 min. Whole-body QAR was carried out using 25-microns thick sections. RESULTS: Fusion images allowed direct comparison of 14C-CHC uptake in tumor and nontumor tissues. Mean 14C-CHC distribution in sensitive and resistant tumors was 882.0 +/- 43.6 and 399.6 +/- 157.7 nCi/g corresponding to 24.5 +/- 1.21 and 11.1 +/- 4.38 nmole/g, respectively (p < 0.001), with normal tissue distribution in both groups being similar. Three-dimensional QAR showed that the uptake of 14C-CHC was in the cellular zones of the tumor. This method has potential in biodistribution studies of novel radiopharmaceuticals such as 14C-CHC. CONCLUSION: These studies further suggest that PET imaging of 11C-CHC is feasible to distinguish between sensitive and resistant tumor deposits in vivo.