title: 18F-Radiolabeling, preliminary evaluation of folate-pHPMA conjugates via PET.
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.
authors.affiliation: Institute of Nuclear Chemistry, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Hanno
authors.initials: H
authors.lastname: Schieferstein
authors.forename: Annette
authors.initials: A
authors.lastname: Kelsch
authors.forename: Achim
authors.initials: A
authors.lastname: Reibel
authors.forename: Kaloian
authors.initials: K
authors.lastname: Koynov
authors.forename: Matthias
authors.initials: M
authors.lastname: Barz
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Buchholz
authors.forename: Nicole
authors.initials: N
authors.lastname: Bausbacher
authors.forename: Oliver
authors.initials: O
authors.lastname: Thews
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zentel
authors.forename: Tobias L
authors.initials: TL
authors.lastname: Ross
mesh_terms: D000818:Animals; D001557:Benzenesulfonates / Q000737:chemistry; D002264:Carboxylic Acids; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000138:chemical synthesis* / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D005462:Fluorine Radioisotopes; D058973:Folate Receptors, GPI-Anchored / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism*; D015870:Gene Expression; D007553:Isotope Labeling; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D058990:Molecular Targeted Therapy; D011109:Polymethacrylic Acids / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods; D051381:Rats; D014018:Tissue Distribution; D014439:Tyramine / Q000737:chemistry
chemical_list: D001557:Benzenesulfonates; D002264:Carboxylic Acids; D003287:Contrast Media; D004337:Drug Carriers; D005462:Fluorine Radioisotopes; D058973:Folate Receptors, GPI-Anchored; C436864:Oregon Green 488 carboxylic acid; D011109:Polymethacrylic Acids; C011533:Duxon; D005492:Folic Acid; D014439:Tyramine
keywords: HPMA; PET; Walker-256 carcinoma; fluorine-18; folate; targeting