Safety, biodistribution, and dosimetry of 123I-IMPY: a novel amyloid plaque-imaging agent for the diagnosis of Alzheimer's disease.
(123)I-IMPY (6-iodo-2-(4'-dimethylamino-)phenyl-imidazo[1,2-a]pyridine) is a novel radiopharmaceutical that selectively binds to Alzheimer's disease (AD) amyloid plaques. As a first step toward validating this radiopharmaceutical as an imaging biomarker for AD, we measured the whole-body biokinetics and radiation dosimetry of (123)I-IMPY in AD patients and cognitively normal control subjects. The pharmacologic safety profile of the compound was simultaneously assessed.


METHODS
The sample included 9 subjects ranging in age from 44 to 80 y. Whole-body images were obtained for each subject (mean +/- SD, 9.0 +/- 3.2 scans per subject) for up to 48 h after the intravenous administration of 185 MBq (5 mCi) of (123)I-IMPY. The fraction of administered activity in 12 regions of interest was quantified from the attenuation-corrected geometric mean counts in conjugate views. Multiexponential functions were iteratively fit to each time-activity curve using a nonlinear, least-squares regression algorithm. These curves were numerically integrated to yield cumulated activity values for source organs. Radiation doses were then estimated with the MIRD technique.


RESULTS
The radiotracer had no pharmacologic effects (produced no changes in heart rate, blood pressure, or laboratory results) on any of the subjects. Radiation dosimetry estimates indicated that the dose-limiting organ was the gallbladder, which received an average of 0.135 mGy/MBq (range, 0.075-0.198 mGy/MBq). The effective dose equivalent and effective dose for (123)I-IMPY were 0.042 +/- 0.003 mSv/MBq and 0.035 +/- 0.001 mSv/MBq, respectively. The mean effective dose for (123)I-IMPY was similar to that for (111)In-diethylenetriaminepentaacetic acid (0.035 mGy/MBq), less than half that for (111)In-pentetreotide (0.81 mGy/MBq), and approximately twice that for (123)I-IMP (0.018 mGy/MBq). No significant differences were found between men and women or between AD patients and control subjects.


CONCLUSIONS
(123)I-IMPY may be a safe radiotracer with appropriate biokinetics for imaging amyloid plaques in AD patients.
Newberg
Andrew B
AB
Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. andrew.newberg@uphs.upenn.edu
Wintering
Nancy A
NA
Plössl
Karl
K
Hochold
John
J
Stabin
Michael G
MG
Watson
Marianne
M
Skovronsky
Daniel
D
Clark
Christopher M
CM
Kung
Mei-Ping
MP
Kung
Hank F
HF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D000682:Amyloid / Q000737:chemistry*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D008956:Models, Chemical; D011720:Pyrazoles; D011874:Radiometry / Q000379:methods*; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D051598:Whole Body Imaging
D000682:Amyloid; D007457:Iodine Radioisotopes; D011720:Pyrazoles; C000971:2,3-dihydro-1H-imidazo(1,2-b)pyrazole