Synthesis and biodistribution of 211At-labeled, biotinylated, and charge-modified poly-L-lysine: evaluation for use as an effector molecule in pretargeted intraperitoneal tumor therapy.
Artikel i vetenskaplig tidskrift, 2002

Poly-L-lysine (7, 21, and 204 kDa) has been evaluated as an effector carrier for use in pretargeted intraperitoneal tumor therapy. For the synthesis, the epsilon-amino groups on the poly-L-lysine were modified in three steps utilizing conjugate biotinylation with biotin amidocaproate N-hydroxysuccinimide ester (BANHS), conjugate radiolabeling with (211)At using the intermediate reagent N-succinimidyl 3-(trimethylstannyl)benzoate (m-MeATE), and charge modification using succinic anhydride, resulting in an increase in the molecular weight of approximately 80% of the final product. The labeling of the m-MeATE reagent and subsequent conjugation of the polymer were highly efficient with overall radiochemical yields in the range of 60-70%. The in vitro avidin binding ability of the modified polymer was almost complete (90-95%), as determined by binding to avidin beads using a convenient filter tube assay. Following intraperitoneal (ip) injection in athymic mice, the 13 kDa polymer product was cleared mainly via the kidneys with fast kinetics (biological half-live T(b) approximately 2 h) and with low whole-body retention. The clearance of the 38 kDa polymer was distributed between kidneys and liver, and the 363 kDa polymer was mainly sequestered by the liver with a T(b) of 8 h. Increased tissue uptake in the thyroid, lungs, stomach, and spleen following the distribution of the large effector molecules (38 and 363 kDa) suggests that degradation of the polymers by the liver may release some of the label as free astatine/astatide.

chemistry

Liver

Mice

chemistry

Nude

pharmacokinetics

pharmacokinetics

Astatine

Aminocaproic Acids

metabolism

Benzoates

chemistry

Biotinylation

Injections

Drug Carriers

Avidin

Polylysine

Intraperitoneal

chemistry

Biotin

chemistry

Female

Inbred BALB C

Trimethyltin Compounds

chemical synthesis

chemistry

Mice

Polymers

Animals

metabolism

Half-Life

Mice

analogs & derivatives

Tissue Distribution

Författare

Sture Lindegren

Göteborgs universitet

Håkan Andersson

Göteborgs universitet

Lars Jacobsson

Göteborgs universitet

Tom Bäck

Göteborgs universitet

Gunnar Skarnemark

Chalmers, Institutionen för material- och ytkemi, Kärnkemi

Börje Karlsson

Göteborgs universitet

Bioconjugate Chemistry

1043-1802 (ISSN) 1520-4812 (eISSN)

Vol. 13 502-9

Ämneskategorier

Fysiologi

Radiologi och bildbehandling

PubMed

12009939