PEG-like Multimodal Nanoprobes (PMN's) are passively targeted nanomaterials for determining the mechanism of retention obtained with enhanced permeability and retention (EPR), for imaging and modeling EPR pre-clinically, and for the eventual imaging of the EPR biomarker in the clinic. EPR is the slow accumulation (12-72 h post injection) of long-circulating nanomedicines (e.g. drug-polymer conjugates, liposomes) in tumors and inflammatory lesions. PMN's consist of DOTA, a PEG, and a fluorochrome attached to a (DOTA)Lys-Cys scaffold. PEG improves fluorochrome performance and endows a PMN with a PEG- determined (rather than fluorochrome-determined) behavior in biological systems. PMN's differ from other EPR nanoprobes (liposomes, albumin, dextrans) by exhibiting a surprising renal (rather than hepatic) elimination, even when the PEG determined dimensions of a PMN exceed the size limit of glomerular filtration, and even when the PMN exhibits the extremely slow whole body clearance needed for a large EPR uptake. The PMN's fluorochrome allows fluorescence-based determination of PMN in tissues (post injection microscopy) or cultured cells (FACS), and will be used to determine the mechanism of PMN retention. DOTA allows 111In3+ radiolabeling for modeling EPR by SPECT and for eventual clinical imaging by SPECT or PET. PMN-EPR imaging maybe employed for the primary detection of tumors or inflammatory lesions, or to stratify patients for the use of long circulating nanomedicines (e.g. liposomes) used in the treatment of their cancer or arthritis.

Public Health Relevance

PEG-like Multimodal Nanoprobes (PMN's) are passively targeted nanomaterials for imaging and modeling enhanced permeability retention (EPR) pre-clinically, and for the eventual imaging of the in the clinic. PMN fluorescence will be used to elucidate the mechanism of PMN retention, while 111In3+ labeled PMN will be used for pre-clinical (and eventual clinical) imaging of EPR by SPECT. PMN-EPR imaging will be used for primary detection or to stratify patients for whom EPR-based nanomedicines (e.g. long circulating liposomes) are being considered for the treatment of their cancer or arthritis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB017699-01
Application #
8610478
Study Section
Clinical Molecular Imaging and Probe Development (CMIP)
Program Officer
Sastre, Antonio
Project Start
2014-09-22
Project End
2018-05-31
Budget Start
2014-09-22
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$424,882
Indirect Cost
$152,373
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199