The effect of internalizing human single chain antibody fragment on liposome targeting to epithelioid and sarcomatoid mesothelioma.
Immunoliposomes (ILs) anchored with internalizing human antibodies capable of targeting all subtypes of mesothelioma can be useful for targeted imaging and therapy of this malignant disease. The objectives of this study were to evaluate both the in vitro and in vivo tumor targeted internalization of novel internalizing human single chain antibody (scFv) anchored ILs on both epithelioid (M28) and sarcomatoid (VAMT-1) subtypes of human mesothelioma. ILs were prepared by post-insertion of mesothelioma-targeting human scFv (M1) onto preformed liposomes and radiolabeled with (111)In ((111)In-IL-M1), along with control non-targeted liposomes ((111)In-CL). Incubation of (111)In-IL-M1 with M28, VAMT-1, and a control non-tumorigenic cell line (BPH-1) at 37 °C for 24 h revealed efficient binding and rapid internalization of ILs into both subtypes of tumor cells but not into the BPH-1 cells; internalization accounted for approximately 81-94% of total cell accumulation in mesothelioma cells compared to 37-55% in control cells. In tumor-bearing mice intravenous (i.v.) injection of (111)In-IL-M1 led to remarkable tumor accumulation: 4% and 4.7% injected dose per gram (% ID/g) for M28 and VAMT-1 tumors, respectively, 48 h after injection. Furthermore, tumor uptake of (111)In-IL-M1 in live xenograft animal models was verified by single photon emission computed tomography (SPECT/CT). In contrast, i.v. injection of (111)In-CL in tumor-bearing mice revealed very low uptake in both subtypes of mesothelioma, 48 h after injection. In conclusion, M1 scFv-anchored ILs showed selective tumor targeting and rapid internalization into both epithelioid and sarcomatoid subtypes of human mesothelioma, demonstrating its potential as a promising vector for enhanced tumor drug targeting.
Center for Molecular and Functional Imaging, Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, CA 94143, USA.
Arun K
AK
Iyer
Yang
Y
Su
Jinjin
J
Feng
Xiaoli
X
Lan
Xiaodong
X
Zhu
Yue
Y
Liu
Dongwei
D
Gao
Youngho
Y
Seo
Henry F
HF
Vanbrocklin
V
V
Courtney Broaddus
Bin
B
Liu
Jiang
J
He
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis; D006801:Humans; D057446:Hydrodynamics; D007205:Indium Radioisotopes; D008081:Liposomes / Q000276:immunology*; D008654:Mesothelioma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D010316:Particle Size; D012509:Sarcoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D057127:Single-Chain Antibodies / Q000378:metabolism*; D055672:Static Electricity; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
D007205:Indium Radioisotopes; D008081:Liposomes; D057127:Single-Chain Antibodies
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