Pancreatic receptors: initial feasibility studies with a targeted contrast agent for MR imaging.
OBJECTIVE
To evaluate cholecystokinin (CCK) as a target-specific vector for magnetic resonance (MR) receptor imaging of rat pancreas.


METHODS
Monocrystalline iron oxide (MION) was labeled with CCK by noncovalent attachment. Receptor specificity of the conjugate was determined with competitive binding studies. Pharmacologic determinations were blood half-lives, biodistribution, time responses, dose responses, and limited toxicity.


RESULTS
Specific cell binding of MION-20-CCK was saturable and inhibitable by a CCK antagonist. Blood half-life of MION-20-CCK was 20 minutes, which was shorter than that of unlabeled MION. Biodistribution studies showed a statistically significant decrease in relaxation times in pancreatic tissues from 42.7 msec +/- 2.0 to 33.8 msec +/- 1.4 (P < or = .05) but not in tumor after administration of MION-20-CCK. The half-life of MION-20-CCK in the pancreas was 3 weeks; no signs of toxicity were shown at the level tested.


CONCLUSIONS
Target-specific MR imaging of pancreatic receptors is feasible. Additional studies are necessary to perfect binding strategies, optimize preparations, and scale up synthesis for imaging in other species.
Department of Radiology, MGH-NMR Center, Massachusetts General Hospital, Boston.
P
P
Reimer
R
R
Weissleder
T
T
Shen
W T
WT
Knoefel
T J
TJ
Brady
D000208:Acute Disease; D000818:Animals; D002766:Cholecystokinin; D003287:Contrast Media / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D052203:Ferrosoferric Oxide; D007501:Iron / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000175:diagnosis; D009368:Neoplasm Transplantation; D010087:Oxides / Q000493:pharmacokinetics; D010179:Pancreas / Q000033:anatomy & histology* / Q000378:metabolism; D010195:Pancreatitis / Q000175:diagnosis; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000378:metabolism
D003287:Contrast Media; D010087:Oxides; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; D007501:Iron; D052203:Ferrosoferric Oxide