Kinetics of111In-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.

Targeting the Nucleus: An Overview of Auger-Electron Radionuclide Therapy

“…In easily forms a complex with bleomycin ( 111 In-BLMC) [111,112], and it has been observed to be a tumourtargeting agent in head-and-neck squamous cell carcinoma and glioma patients, thus being a useful diagnostic tracer [113][114][115][116]. In an autoradiography study by Hou and Maruyama, 78% of 111 In-BLMC was localised in the nucleus and nuclear membrane of human small cell lung cancer cells [117,118].…”

Review of microdialysis in brain tumors, from concept to application: First Annual Carolyn Frye-Halloran Symposium

“…Most drugs administered systemically for the treatment of brain tumors have properties that promote passage across the barrier such as low molecular weight (Ͻ200 Da), lipophilicity, and low proteinbinding capability (Rall and Zubrod, 2000). It is likely that the barrier is disrupted in a nonhomogeneous fashion, permitting the passage of some agents (bleomycin, nitrosoureas, and platinum compounds) into tumors (Hargrave et al, 2002;Korppi-Tommola et al, 1999;Roche et al, 2000;Ryynanen et al, 1998;Tokunaga et al, 2000). The techniques used to show brain delivery of these compounds involve tissue analyses from biopsies, which provide minimal data concerning distribution kinetics or activated drug levels within tumor and/or its distant infiltrates.…”