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

摘要: Absorbed dose profiles within tumor spheroids simulating avascular micrometastases have been calculated for a variety of liposome- and antibody-radionuclide combinations to assess the anticipated therapeutic efficacy based on intratumoral distribution carrier systems spheroid model. Methods: Experiments studying targeting diffusion capability most clinically relevant liposome anti-PSMA (prostate-specific membrane antigen) antibody J591 prostate cancer cell line LNCaP (diameter, 150–200 μm) performed. The biodistribution data were then used as input obtain absorbed mass. dosimetric analysis was performed medium- high-energy β-emitting radionuclides (32P, 90Y, 188Re, 67Cu, 131I) 2 low-energy Auger or conversion electron emitters (123I, 125I) following point-kernel convolution method in continuous slowing-down approximation. Results: Relative calculations function distance from rim are presented. For all studied, SUV-DMPC-chol (small unilamellar vesicle-dimyristoyl-phosphatidylcholine-cholesterol) efficient penetrating deeper spheroids. β-emitters it delivered its maximum (Dmax) at 40- 50-μm depth, exhibiting an almost flat profile beyond that point, is evident by high value center (Dcore), Dcore/Dmax > 0.9; respective values 20 μm 0.85. resulted heterogeneous distribution; ratio fell 0.4 0.4–0.5 antibody. In general, 2- 10-fold “cross-fire”-related increase core observed. liposomes binding capacity (3β-[N-(N′,N′]-dimethylaminoethane)carbamoyl]cholesterol [DC-chol]), however, deliver up 40% higher Dmax relative β-emitters. surface characteristics appear noticeable influence profiles. use neutral (DMPC-chol) versus cationic (DC-chol) lipids depending radionuclide. Changing lipid N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl sulfate also had notable (up 6-fold increase), whereas effect fusogenic (dioleoylphosphatidylcholine) found be much smaller. Conclusion: It possible engineer particularly effective delivering uniform central region micrometastatic tumors, provided conjugates with appropriate constructed. view passive means solid suggested they may effectively complement antibody-based regime against leading cytotoxic levels throughout entire volume—thus, hindering recurrence.