title: Kinetics of 111In-labeled bleomycin in patients with brain tumors: compartmental vs. non-compartmental models.
abstract: The kinetics of an indium-111 labeled bleomycin complex (111In-BLMC) after rapid intravenous injection in patients with brain tumors was quantified by using compartmental and non-compartmental models. The models were applied to data obtained from 10 glioma, one meningioma, and one adenocarcinoma brain metastasis patients. Blood and urine samples from all the patients and tumor samples from three patients were collected. The mean transit time of 111In-BLMC in the plasma pool was 14 +/- 7 min without and 1.8 +/- 0.6 h when accounting for recirculation, and 13 +/- 4 h in the total body pool. The mean plasma clearance of 111In-BLMC was 0.3 +/- 0.1 m/blood/min and the mean half-life in urine was 3.5 +/- 0.6 h. The mean transfer coefficients for the open three-compartmental model were: excretion from plasma = 0.02 +/- 0.01, from depot to plasma = (12 +/- 9)*10(-4), from plasma to depot = 0.01 +/- 0.01, from tumor to plasma = 0.39 +/- 0.19 and from plasma to tumor = 1.11 +/- 0.57, all in units minute-1. The mean turnover time from the tumor was 4.5 +/- 2.7 min and from the depot 20 +/- 8 h. It is concluded that both compartmental and non-compartmental models are sufficient to describe the kinetics of indium-111 labeled bleomycin complex. The non-compartmental model is more practical and to some extent more efficient in describing the in vivo behaviors of 111In-BLMC than the compartmental model. The compartmental model used provides estimates of both extraction and excretion from the plasma and tumor.
authors.affiliation: Department of Physics, University of Helsinki, Finland.
authors.forename: P M
authors.initials: PM
authors.lastname: Ryynänen
authors.forename: S E
authors.initials: SE
authors.lastname: Savolainen
authors.forename: H J
authors.initials: HJ
authors.lastname: Aronen
authors.forename: E T
authors.initials: ET
authors.lastname: Korppi-Tommola
authors.forename: H M
authors.initials: HM
authors.lastname: Huhmar
authors.forename: M E
authors.initials: ME
authors.lastname: Kallio
authors.forename: J V
authors.initials: JV
authors.lastname: Hiltunen
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D001932:Brain Neoplasms / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D005260:Female; D005910:Glioma / Q000378:metabolism; D006801:Humans; D007205:Indium Radioisotopes / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008579:Meningioma / Q000378:metabolism / Q000556:secondary; D008875:Middle Aged; D008954:Models, Biological; D009942:Organometallic Compounds / Q000097:blood / Q000493:pharmacokinetics*