Iodine-124 as a Label for Pharmacological PET Imaging

被引:28
作者
Belov, Vasily V. [1 ,2 ,3 ]
Bonab, Ali A. [1 ,2 ,3 ]
Fischman, Alan J. [2 ,3 ]
Heartlein, Michael [4 ]
Calias, Pericles [4 ]
Papisov, Mikhail I. [1 ,2 ,3 ]
机构
[1] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Boston, MA USA
[3] Shriners Burns Hosp Boston, Boston, MA USA
[4] Shire Human Genet Therapy, Lexington, MA USA
关键词
Iodine-124; Positron Emission Tomography; Pharmacology; Pharmacokinetics; Biopharmaceuticals; Macromolecules; POSITRON-EMISSION-TOMOGRAPHY; PERFORMANCE EVALUATION; SPATIAL-RESOLUTION; SCANNER; SYSTEM; SENSITIVITY; EMITTERS;
D O I
10.1021/mp100358f
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
With the growing number of biotechnology products and drug delivery systems entering preclinical and clinical studies, pharmacological imaging studies with PET play an increasingly significant role. Such studies often require investigation of slow and complex pharmacokinetics (PK). This suggests labeling of the drug candidate with radionuclides that have long physical half-lives. Among the currently available PET positron emitters, (124)1 has the longest physical half-life (4.2 days). This, combined with the well-investigated behavior of iodine in vivo, makes I-124 very attractive for pharmacological studies. However, the high energy of the positrons emitted by I-124 and the presence of single photons in the I-124 emission can potentially introduce limitations in the quantitative analysis of the images. The objective of this research was to determine whether the use of I-124 as a PET label provides data quality suitable for PK studies. The study was carried out using MicroPET P4 scanner (Siemens/Concorde Microsystems). Spatial resolution, count-rate performance, sensitivity and scatter fraction were measured using a line source and a cylindrical phantom. Model animal studies in rats and cynomolgus monkeys were carried out using human recombinant proteins. The proteins were labeled with I-124, up to 185 MBq/mg. The transaxial and axial spatial resolutions in the center of the camera were satisfactory and higher for OSEM3D/MAP than FORE-2DFBP (FWHM 2.52 vs 3.31 mm, and 3.10 vs 3.69 mm). Linearity of the true coincidence count-rate was observed up to 44 MBq. Animal studies demonstrated excellent delineation and resolution of even very small organs. At optimal doses, 2-10 MBq per animal for rodents and 4-10 MBq per kg of body weight for larger animals, the quality of numerical data was appropriate for PK analysis in all experimental timeframes from minutes (dynamic studies) to 10 days. Overall, the data suggest that I-124 is an excellent label for quantitative pharmacological PET imaging studies.
引用
收藏
页码:736 / 747
页数:12
相关论文
共 34 条
[1]  
Casey M. E., 1995, Proceedings of the 1995 International Meeting on Fully Three-Dimensional Image Reconstruction in Radiology and Nuclear Medicine, P67
[2]  
Cherry S. R., 2012, Physics in Nuclear Medicine
[3]  
Daube-Witherspoon ME, 2002, J NUCL MED, V43, P1398
[4]   Exact and approximate rebinning algorithms for 3-D PET data [J].
Defrise, M ;
Kinahan, PE ;
Townsend, DW ;
Michel, C ;
Sibomana, M ;
Newport, DF .
IEEE TRANSACTIONS ON MEDICAL IMAGING, 1997, 16 (02) :145-158
[5]   Iodotyrosine deiodinase is the first mammalian member of the NADH oxidase/flavin reductase superfamily [J].
Friedman, JE ;
Watson, JA ;
Lam, DWH ;
Rokita, SE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (05) :2812-2819
[6]   Optimization and assessment of quantitative 124I imaging on a Philips Gemini dual GS PET/CT system [J].
Gregory, Rebecca A. ;
Hooker, Claire A. ;
Partridge, Mike ;
Flux, Glenn D. .
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2009, 36 (07) :1037-1048
[7]  
Guggenheim EA, 1926, PHILOS MAG, V2, P538
[8]   INFLUENCE OF GASTROINTESTINAL IODIDE CYCLE ON EARLY DISTRIBUTION OF RADIOACTIVE IODIDE IN MAN [J].
HAYS, MT ;
SOLOMON, DH .
JOURNAL OF CLINICAL INVESTIGATION, 1965, 44 (01) :117-&
[9]  
Herzog H, 2008, Q J NUCL MED MOL IM, V52, P159
[10]   PET quantitation and imaging of the non-pure positronemitting iodine isotope 124I [J].
Herzog, H ;
Tellmann, L ;
Qaim, SM ;
Spellerberg, S ;
Schmid, A ;
Coenen, HH .
APPLIED RADIATION AND ISOTOPES, 2002, 56 (05) :673-679