Abstract
The synthesis of a 10.5 kDa and a 52.5 kDa polymer, based on pHPMA functionalized with tyramine for (18) F-labeling and a folate derivative as targeting moiety, is reported. FCS studies are conducted using Oregon Green-labeled conjugates. No aggregation is observed for the 10.5 kDa conjugate, but strong aggregation for the 52.5 kDa conjugate. In vivo studies are conducted using Walker-256 mammary carcinoma model to determine body distribution as function of size and especially targeting unit. These in vivo studies show a higher short time (2 h) accumulation for both conjugates in the tumor than for untargeted pHPMA, confirmed by blockade studies. The 10.5 kDa polymer accumulates with 0.46% ID g(-1) and the 52.5 kDa polymer with 0.28% ID g(-1) in the tumor after 2 h, demonstrating the potential of the folate-targeting concept.
Keywords:
HPMA; PET; Walker-256 carcinoma; fluorine-18; folate; targeting.
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Benzenesulfonates / chemistry
-
Carboxylic Acids
-
Carcinoma / genetics
-
Carcinoma / metabolism
-
Carcinoma / pathology
-
Carcinoma / therapy*
-
Cell Line, Tumor
-
Contrast Media / chemical synthesis*
-
Contrast Media / pharmacology
-
Drug Carriers / chemical synthesis*
-
Drug Carriers / pharmacology
-
Female
-
Fluorine Radioisotopes
-
Folate Receptors, GPI-Anchored / genetics
-
Folate Receptors, GPI-Anchored / metabolism
-
Folic Acid / chemistry
-
Folic Acid / metabolism*
-
Gene Expression
-
Isotope Labeling
-
Mammary Neoplasms, Animal / genetics
-
Mammary Neoplasms, Animal / metabolism
-
Mammary Neoplasms, Animal / pathology
-
Mammary Neoplasms, Animal / therapy*
-
Molecular Targeted Therapy
-
Polymethacrylic Acids / chemistry*
-
Positron-Emission Tomography / methods
-
Rats
-
Tissue Distribution
-
Tyramine / chemistry
Substances
-
Benzenesulfonates
-
Carboxylic Acids
-
Contrast Media
-
Drug Carriers
-
Fluorine Radioisotopes
-
Folate Receptors, GPI-Anchored
-
Oregon Green 488 carboxylic acid
-
Polymethacrylic Acids
-
Duxon
-
Folic Acid
-
Tyramine