Biodistribution and Radiation Dosimetry for the Novel SV2A Radiotracer [18F]UCB-H: First-in-Human Study

被引：38

作者：

Bretin, F. ^{[1
]}

Bahri, M. A. ^{[1
]}

Bernard, C. ^{[3
]}

Warnock, G. ^{[1
]}

Aerts, J. ^{[1
]}

Mestdagh, N. ^{[2
]}

Buchanan, T. ^{[2
]}

Otoul, C. ^{[2
]}

Koestler, F. ^{[2
]}

Mievis, F. ^{[1
]}

Giacomelli, F. ^{[1
]}

Degueldre, C. ^{[1
]}

Hustinx, R. ^{[3
]}

Luxen, A. ^{[1
]}

Seret, A. ^{[1
]}

Plenevaux, A. ^{[1
]}

Salmon, E. ^{[1
]}

机构：

[1] Univ Liege, Cyclotron Res Ctr, B-4000 Liege, Belgium

[2] UCB Pharma, Braine Lalleud, Belgium

[3] Univ Liege, CHU, Nucl Med, B-4000 Liege, Belgium

来源：

MOLECULAR IMAGING AND BIOLOGY | 2015年 / 17卷 / 04期

关键词：

Radiotracer; Human dosimetry; Brain; PET; SV2A; Translational; SYNAPTIC VESICLE PROTEIN; PET TRACERS; RADIOPHARMACEUTICALS; EXPRESSION;

D O I：

10.1007/s11307-014-0820-6

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

[F-18]UCB-H is a novel radiotracer with a high affinity for synaptic vesicle glycoprotein 2A (SV2A), a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a "first-in-class" antiepileptic drug with a distinct but still poorly understood mechanism of action. The objective of this study was to determine the biodistribution and radiation dosimetry of [F-18]UCB-H in a human clinical trial and to establish injection limits according to biomedical research guidelines. Additionally, the clinical radiation dosimetry results were compared to estimations in previously published preclinical data. Dynamic whole body positron emission tomography/X-ray computed tomography (PET/CT) imaging was performed over approximately 110 min on five healthy male volunteers after injection of 144.5 +/- 7.1 MBq (range, 139.1-156.5 MBq) of [F-18]UCB-H. Major organs were delineated on CT images, and time-activity curves were obtained from co-registered dynamic PET emission scans. The bladder could only be delineated on PET images. Time-integrated activity coefficients were calculated as area under the curve using trapezoidal numerical integration. Urinary excretion data based on PET activities including voiding was also simulated using the dynamic bladder module of OLINDA/EXM. The radiation dosimetry was calculated using OLINDA/EXM. The effective dose to the OLINDA/EXM 70-kg standard male was 1.54 x 10(-2) +/- 6.84 x 10(-4) millisieverts (mSv)/MBq, with urinary bladder wall, gallbladder wall, and the liver receiving the highest absorbed dose. The brain, the tracer's main organ of interest, received an absorbed dose of 1.89 x 10(-2) +/- 2.32 x 10(-3) mGy/MBq. This first human dosimetry study of [F-18]UCB-H indicated that the tracer shows similar radiation burdens to widely used common clinical tracers. Single injections of at maximum 672 MBq for US practice and 649 MBq for European practice keep radiation exposure below recommended limits. Recently published preclinical dosimetry data extrapolated from mice provided satisfactory prediction of total body and effective dose but showed significant differences in organ absorbed doses compared to human data.

引用

页码：557 / 564

页数：8

共 34 条

[1]

[Anonymous], 2009, Soc Nucl Med (Version 10)

[2] DIFFERENTIAL EXPRESSION OF SYNAPTIC VESICLE PROTEIN-2 (SV2) ISOFORMS [J].