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Liposome-Mediated Radiotherapeutics Within Avascular Tumor Spheroids: Comparative Dosimetry Study for Various Radionuclides, Liposome Systems, and a Targeting Antibody

¹ Department of Medical Physics, University of Ioannina Medical School, Ioannina, Greece
² Centre for Drug Delivery Research, The School of Pharmacy, University of London, London, United Kingdom
³ Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York
⁴ Department of Radiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland

View larger version (22K): [in a new window]   FIGURE 1. Fluorescent intensity profiles in arbitrary units (a.u.) as function of distance from rim of spheroid at various times after incubation for liposome system MLV (DMPC:DOPE:DOTAP, where DOPE = dioleoylphosphatidylcholine) (A), liposome system SUV (DMPC:chol) (B), and antibody J591 (from bottom to top curve: 1, 2, 3, 18, and 24 h) (C).

View larger version (21K): [in a new window]   FIGURE 2. Fluorescent intensity profiles normalized to their peak values. (A) Liposome systems (average for 2 time points): S1 = SUV DMPC:DC-chol; S2 = SUV DMPC:DOPE:DOTAP (DOPE = dioleoylphosphatidylcholine); S3 = SUV DMPC-chol; M = MLV DMPC:DOPE:DOTAP. (B) J591 antibody.

View larger version (21K): [in a new window]   FIGURE 3. Cumulative absorbed dose distribution profiles normalized to the maximum (D/Dmax) absorbed dose value of the distribution for all electron-emitting radionuclides studied. Boxes are normalized fluorescent profiles of carrier (an average value for all time points was used). (A) MLV (DMPC:DOPE:DOTAP, where DOPE = dioleoylphosphatidylcholine). (B) SUV (DMPC-chol). (C) J591 antibody.

View larger version (20K): [in a new window]   FIGURE 4. Normalized (cumulative) absorbed dose distribution profiles for various carrier systems studied (symbols as in Fig. 2; Ab = antibody) for 2 electron emitters with very different emission characteristics. (A) Low-energy emitter with short half-life: 123I. (B) High-energy ß-emitter with long half-life: 90Y.

View larger version (23K): [in a new window]   FIGURE 5. Absorbed dose profiles in arbitrary units (a.u.) per radionuclide decay calculated for all radionuclides studied for 2 liposome systems. (A) MLV (DMPC:DOPE:DOTAP). (B) SUV (DMPC-chol).

View larger version (23K): [in a new window]   FIGURE 6. Cumulative absorbed dose profiles in arbitrary units (a.u.) calculated for all radionuclides studied for 2 liposome systems. (A) MLV (DMPC:DOPE:DOTAP). (B) SUV (DMPC-chol).