Intraarticular tolerability and kinetics of gadolinium tetra-azacyclododecane tetraacetic acid.
OBJECTIVE
We assessed the tolerability and the intraarticular kinetics of gadolinium tetra-azacyclododecane tetraacetic acid (Gd-DOTA) using magnetic resonance (MR) imaging.


METHODS
Twelve of 18 dogs received an intraarticular injection of Gd-DOTA solution. Pathologic examination of all joints was performed with assessment of Gd-DOTA bone absorption. Effects of Gd-DOTA on chondrocyte viability and proliferation in vitro were determined using cultures of rabbit chondrocytes. Four dogs underwent MR imaging of the stifle joint before and after intraarticular injection of 0.8 ml Gd-DOTA at a concentration of 2 mmol/l (300 mOsm/l). Intraarticular kinetics of Gd-DOTA were determined from quantitative measurements using repeated sagittal spin-echo T1-weighted images.


RESULTS
No microscopic changes of the joints or Gd-DOTA bone absorption were detected. No cytotoxicity for chondrocytes was observed at a concentration of 5 mmol/l, but a decreased cell count was observed at a high concentration (50 mmol/l). The intraarticular Gd-DOTA concentration decreased with time according to a logarithmic curve with an intraarticular half-life of 103-152 min (M = 127 min).


CONCLUSIONS
Gd-DOTA is a safe intraarticular contrast agent with a long half-life in the joint cavity.
Rahmouni
A
A
Department of Radiology, Centre Hospitalo-Universitaire Henri Mondor, Créteil, France.
Mathieu
D
D
Chambon
C
C
Dao
T H
TH
Hernigou
P
P
Vasile
N
N
D000042:Absorption; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004285:Dogs; D004361:Drug Tolerance; D005260:Female; D005500:Follow-Up Studies; D006207:Half-Life; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007270:Injections, Intra-Articular; D007596:Joints / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011817:Rabbits; D012449:Safety; D013264:Stifle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate