title: Evaluation of carbon-14-colchicine biodistribution with whole-body quantitative autoradiography in colchicine-sensitive and -resistant xenografts.
abstract: 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.
  
  
  CONCLUSIONS
  These studies further suggest that PET imaging of 11C-CHC is feasible to distinguish between sensitive and resistant tumor deposits in vivo.
authors.affiliation: Nuclear Medicine Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Mehta
authors.forename: A
authors.initials: A
authors.lastname: Levchenko
authors.forename: E
authors.initials: E
authors.lastname: Rosa
authors.forename: S W
authors.initials: SW
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Winnick
authors.forename: J J
authors.initials: JJ
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Kalaigian
authors.forename: S M
authors.initials: SM
authors.lastname: Larson
mesh_terms: D000818:Animals; D001345:Autoradiography; D002250:Carbon Radioisotopes; D003078:Colchicine / Q000493:pharmacokinetics / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000000981:diagnostic imaging* / Q000188:drug therapy; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014183:Transplantation, Heterologous
chemical_list: D002250:Carbon Radioisotopes; D003078:Colchicine