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Longitudinal investigation of permeability and distribution of macromolecules in mouse tumor development and malignant transformation using PET
Author(s) -
Rygh C B,
Seo J W,
Qin SP,
Mahakian L M,
Zhang H,
Kukis D L,
Chan J Q,
ChengLiao J,
Reed R K,
Ferrara K W
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.592.9
Subject(s) - liposome , in vivo , albumin , biodistribution , chemistry , permeability (electromagnetism) , distribution (mathematics) , clearance , pathology , vascular permeability , drug delivery , medicine , in vitro , biology , biochemistry , membrane , microbiology and biotechnology , organic chemistry , urology , mathematical analysis , mathematics
Liposomes are widely used as carriers of drugs, genes, or contrast agents while albumin is a commonly used tracer for permeability studies. Here we studied the permeability and distribution of 64 Cu‐labeled liposomes and albumin ( 64 Cu‐BAT‐liposomes, Seo et al. Bioconjugate Chem.19: 2577, 2008, and 64 Cu‐BAT‐BSA) in a mouse model of ductal carcinoma in situ. Precancer mammary intraepithelial neoplasia outgrowth (MINO, line 4) tissue was transplanted bi‐laterally into gland cleared mammary fat pads in young FVB/N mice (n=8) and were PET scanned (Focus 120, Siemens Medical Solutions, Inc.) at week 3, 5, 7 and 8 after transplantation. Each animal was scanned at multiple time‐points after bolus injection of the tracer to create time‐activity curves (TACs). The apparent permeability of both tracers increased over time as the lesions transformed, and was higher for albumin than for liposomes (from 3.46 ± 0.69 to 12.48 ± 2.94 and 0.81 ± 0.61 to 2.29 ± 0.56 10 −8 cm/s for albumin and liposomes at week 3 and 8, respectively). In general, the distribution of liposomes within the tumor was more heterogeneous than with albumin. In conclusion, longitudinal progression of disease could be detected in vivo with PET imaging, as well as heterogeneity of tracer permeability and distribution within the lesions which is valuable information when evaluating drug‐delivery efficacy. This project was supported by NIH CA 103828 and CA 134659