Imaging of exocrine pancreatic function. Investigation of the bioavailability of weak organic acids as potential pancreatic contrast agents for computed tomography.
OBJECTIVE
The feasibility of targeting iodinated contrast agents to the exocrine pancreas was investigated. Iodinated weak organic acids including succinic acid-mono-3-amino-2,4,6-triiodo- N-ethylanilide (compound I), the ethanolamine salt of N-ethylsuccinic acid-(2,4,6-triiodo-3-methylamino anilide) (compound II), and the sodium salt of 2,4,6-triiodo-3-N-ethylacetylamino-phenylpropionic acid (compound III) were studied as potential contrast agents for computed tomography (CT) of the pancreas.


METHODS
An ex vivo perfusion system was used to compare pancreatic uptake of the three compounds. In vivo CT studies were conducted using domestic pigs to study potential enhancement of the pancreas after intravenous injection of the compound.


RESULTS
Ex vivo perfusion studies with isolated rat pancreas demonstrated nearly identical extraction ratios of approximately 0.6 for all three compounds tested. Average iodine concentrations measured in pancreas at the end of the perfusion studies was 0.27 mg/g +/- 0.20 for compound I, 0.18 mg/g +/- 0.06 for compound II, and 0.16 mg/g +/- 0.09 for compound III. Differences in iodine concentrations retained were not statistically significant. Computed tomography studies in domestic pigs demonstrated up to 30% enhancement of the pancreas after intravenous injection of 75 and 150 mg/kg of compound II at 45 minutes. Whereas ex vivo perfusion studies indicated increasing extraction of the three compounds with increasing doses/concentrations in the perfusate, no improved contrast enhancement was observed at the higher dose level compared with the lower dose in CT.


CONCLUSIONS
Both ex vivo perfusion studies and dose-independent enhancement levels achieved seem to indicate a transport maximum in the pancreas for the iodinated weak organic acids studied.
Department of Radiology, University of Washington, School of Medicine, Seattle 98195.
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U
Schmiedl
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Schmoll
J
J
Horn
U
U
Speck
P
P
Freeny
D000813:Anilides / Q000008:administration & dosage / Q000493:pharmacokinetics; D000814:Aniline Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D002445:Celiac Artery; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007455:Iodine / Q000032:analysis / Q000493:pharmacokinetics; D008297:Male; D010179:Pancreas / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000378:metabolism*; D010666:Phenylpropionates / Q000008:administration & dosage / Q000493:pharmacokinetics; D011856:Radiographic Image Enhancement / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013386:Succinates / Q000008:administration & dosage / Q000493:pharmacokinetics; D013552:Swine; D014057:Tomography, X-Ray Computed
C090599:2,4,6-triiodo-3-N-ethylacetylaminophenylpropionic acid; D000813:Anilides; D000814:Aniline Compounds; D003287:Contrast Media; C090598:N-ethylsuccinic acid 2,4,6-triiodo-3-methylaminoanilide; D010666:Phenylpropionates; D013386:Succinates; C090597:succinic acid mono-3-amino-2,4,6-triiodo-N-ethylanilide; D007455:Iodine