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Uptake of 99mTc-labeled chondroitin sulfate by chondrocytes and cartilage: a promising agent for imaging of cartilage degeneration?

Abstract：

:Chondroitin sulfate (CS) is used in the treatment of human osteoarthritis as a slow-acting symptomatic drug. For this reason, we performed uptake studies with (99m)TcCS using different chondrocyte cultures, as well as cartilage tissue in vitro. For uptake studies, adherent monolayer cultures of human chondrocytes (2.7 x 10(4) cells/well) and (99m)TcCS (1 microCi) were used. In parallel, we also performed uptake studies with cell suspensions of human chondrocytes at 1 x 10(6) cells/well incubated with (99m)TcCS (5 microCi) under identical conditions. Uptake was studied also in cartilage tissue samples and frozen tissue sections for autoradiography. The uptake was monitored for 10-240 min, every 10-30 min for cell cultures and for cartilage tissue up to 72 h. As the commercially available drug Condrosulf (IBSA, Lugano, Switzerland) contains magnesium (Mg) stearate as additive, we investigated the uptake with and without this additive. The washout of the tracer was assessed after the uptake experiments with PBS buffer for different time intervals (10 min-3 h). Tracer uptake in monolayer+/-additives with low number of cells was low. With the use of chondrocytes in culture suspensions with higher number of cells, a higher uptake of 5.9+/-0.65% and 1.0+/-0.1% (n=6) was found, with and without additive, respectively. The saturation was achieved after 100 min. With the use of human rib cartilage, the uptake of (99m)TcCS was continuously increasing with time and was very high with additive amounting to 101.8+/-5.2% vs. 53.0+/-8.3% (n=6) without after 72 h and showing delayed saturation up to 30 h. Thus, not only the resorption of the drug is enhanced by Mg-stearate, but also the uptake. The washout of the tracer from cartilage after 3 h of uptake amounted to 3.75+/-1.5% with additive vs. 13.1+/-2.1% without. After 24 h, washout was lower amounting to 1.75+/-0.15% vs. 3.25+/-0.25%, respectively. The autoradiographic studies paralleled the results of in vitro cartilage tissue uptake. These data show that (99m)TcCS accumulates in cartilage tissue, either by acting as a substrate for proteoglycan synthesis or by adsorption to cartilage. (99m)TcCS could therefore be a possible agent to target and radioimage osteoarthritis.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

Sobal G,Menzel J,Sinzinger H

doi

10.1016/j.nucmedbio.2008.10.013

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

65-71

issue

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(08)00233-3

journal_volume

pub_type

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Uptake of 99mTc-labeled chondroitin sulfate by chondrocytes and cartilage: a promising agent for imaging of cartilage degeneration?