Chiral porphyrazine near-IR optical imaging agent exhibiting preferential tumor accumulation.
A chiral porphyrazine (pz), H(2)[pz(trans-A(2)B(2))] (247), has been prepared that exhibits preferential in vivo accumulation in the cells of tumors. Pz 247 exhibits near-infrared (NIR) emission with lambda > 700 nm in the required wavelength range for maximum tissue penetration. When MDA-MB-231 breast tumor cells are treated with 247, the agent shows strong intracellular fluorescence with an emission maximum, 704 nm, which indicates that it localizes within a hydrophobic microenvironment. Pz 247 is shown to associate with the lipophilic core of LDL and undergo cellular entry primarily through receptor-mediated endocytosis accumulating in lysosomes. Preliminary in vivo studies show that 247 exhibits preferential accumulation and retention in the cells of MDA-MB-231 tumors subcutaneously implanted in mice, thereby enabling NIR optical imaging with excellent contrast between tumor and surrounding tissue. The intensity of fluorescence from 247 within the tumor increases over time up to 48 h after injection presumably due to the sequestration of circulating 247/LDL complex by the tumor tissue. As the need for cholesterol, and thus LDL, is elevated in highly proliferative tumor cells over nontumorigenic cells, 247 has potential application for all such tumors.
Trivedi
Evan R
ER
Departments of Chemistry, Northwestern University, Evanston, IL 60208, USA.
Harney
Allison S
AS
Olive
Mary B
MB
Podgorski
Izabela
I
Moin
Kamiar
K
Sloane
Bonnie F
BF
Barrett
Anthony G M
AG
Meade
Thomas J
TJ
Hoffman
Brian M
BM
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D015394:Molecular Structure; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D011166:Porphyrins / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D019265:Spectroscopy, Near-Infrared; D013237:Stereoisomerism; D014183:Transplantation, Heterologous
D007211:Indoles; D011166:Porphyrins