Direct comparison of radiation dosimetry of six PET tracers using human whole-body imaging and murine biodistribution studies

ObjectiveWe investigated the whole-body biodistributions and radiation dosimetry of five 11C-labeled and one 18F-labeled radiotracers in human subjects, and compared the results to those obtained from murine biodistribution studies.MethodsThe radiotracers investigated were 11C-SA4503, 11C-MPDX, 11C-TMSX, 11C-CHIBA-1001, 11C-4DST, and 18F-FBPA. Dynamic whole-body positron emission tomography (PET) was performed in three human subjects after a single bolus injection of each radiotracer. Emission scans were collected in two-dimensional mode in five bed positions. Regions of interest were placed over organs identified in reconstructed PET images. The OLINDA program was used to estimate radiation doses from the number of disintegrations of these source organs. These results were compared with the predicted human radiation doses on the basis of biodistribution data obtained from mice by dissection.ResultsThe ratios of estimated effective doses from the human-derived data to those from the mouse-derived data ranged from 0.86 to 1.88. The critical organs that received the highest absorbed doses in the human- and mouse-derived studies differed for two of the six radiotracers. The differences between the human- and mouse-derived dosimetry involved not only the species differences, including faster systemic circulation of mice and differences in the metabolism, but also measurement methodologies.ConclusionsAlthough the mouse-derived effective doses were roughly comparable to the human-derived doses in most cases, considerable differences were found for critical organ dose estimates and pharmacokinetics in certain cases. Whole-body imaging for investigation of radiation dosimetry is desirable for the initial clinical evaluation of new PET probes prior to their application in subsequent clinical investigations.

[1]  K. Någren,et al.  Human Dosimetry of Carbon-11 Labeled N-butan-2-yl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide Extrapolated from Whole-body Distribution Kinetics and Radiometabolism in Rats , 2010, Molecular Imaging and Biology.

[2]  Robert B. Innis,et al.  Suggested pathway to assess radiation safety of 11C-labeled PET tracers for first-in-human studies , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[3]  H. Thierens,et al.  Biodistribution and dosimetry of carbon-11-methoxyprogabidic acid, a possible ligand for GABA-receptors in the brain. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[4]  Icrp ICRP Publication 60: 1990 Recommendations of the International Commission on Radiological Protection , 1991 .

[5]  H. Herzog,et al.  Whole-body distribution and dosimetry of O-(2-[18F]fluoroethyl)-l-tyrosine , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[6]  B F Hutton,et al.  Simultaneous emission and transmission measurements for attenuation correction in whole-body PET. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[7]  G. Firnau,et al.  Estimation of the radiation dose in man due to 6-[18F]fluoro-L-dopa. , 1985, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[8]  K. Hashimoto,et al.  Biodistribution and radiation dosimetry of the α7 nicotinic acetylcholine receptor ligand [11C]CHIBA-1001 in humans. , 2011, Nuclear medicine and biology.

[9]  D. J. Valentin 3. Recalculated dose data for 19 frequently used radiopharmaceuticals from ICRP Publication 53 , 1998 .

[10]  Yuichi Kimura,et al.  Preclinical studies on [11C]TMSX for mapping adenosine A2A receptors by positron emission tomography , 2003, Annals of nuclear medicine.

[11]  R. Dannals,et al.  PET imaging of brain acetylcholinesterase using [11C]CP‐126,998, a brain selective enzyme inhibitor , 2002, Synapse.

[12]  Michael G Stabin,et al.  OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[13]  S. Huskey,et al.  Species differences in N-glucuronidation. , 1998, Drug metabolism and disposition: the biological fate of chemicals.

[14]  M. Senda,et al.  11C-labeled KF18446: a potential central nervous system adenosine A2a receptor ligand. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[15]  H. Watabe,et al.  Absorbed dose estimates in positron emission tomography studies based on the administration of 18F-labeled radiopharmaceuticals. , 1991, Journal of radiation research.

[16]  M. Senda,et al.  Preclinical evaluation of [11C]SA4503: radiation dosimetry,in vivo selectivity and PET imaging of sigma1 receptors in the cat brain , 2000, Annals of nuclear medicine.

[17]  H. Minn,et al.  Biodistribution and radiation dosimetry of [11C]choline: a comparison between rat and human data , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[18]  Jan Passchier,et al.  Radiation dose estimates for carbon-11-labelled PET tracers. , 2012, Nuclear medicine and biology.

[19]  J. Hirvonen,et al.  Human biodistribution and radiation dosimetry of 11C-(R)-PK11195, the prototypic PET ligand to image inflammation , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[20]  Ming-fang Wang,et al.  Pharmacokinetics and radiation dosimetry estimation of O-(2-[18F]fluoroethyl)-L-tyrosine as oncologic PET tracer. , 2003, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[21]  Masatoshi Itoh,et al.  Estimation of absorbed dose for 2-[F-18]fluoro-2-deoxy-d- glucose using whole-body positron emission tomography and magnetic resonance imaging , 1998, European Journal of Nuclear Medicine.

[22]  W. Beierwaltes,et al.  Radiation Dosimetry of 131I-19-Iodocholesterol: The Pitfalls of Using Tissue Concentration Data—Reply , 1975 .

[23]  J. Lin,et al.  Species similarities and differences in pharmacokinetics. , 1995, Drug metabolism and disposition: the biological fate of chemicals.

[24]  A. D. Roberts,et al.  Fluorine-18-fluoro-L-DOPA dosimetry with carbidopa pretreatment. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[25]  K. Hashimoto,et al.  Preclinical and the first clinical studies on [11C]CHIBA-1001 for mapping α7 nicotinic receptors by positron emission tomography , 2009, Annals of nuclear medicine.

[26]  Kazutoshi Suzuki,et al.  Feasibility studies of 4'-[methyl-(11)C]thiothymidine as a tumor proliferation imaging agent in mice. , 2008, Nuclear medicine and biology.

[27]  Tadashi Nariai,et al.  Preclinical studies on [11C]MPDX for mapping adenosine A1 receptors by positron emission tomography , 2002, Annals of nuclear medicine.

[28]  K. Ishii,et al.  Whole-Body Distribution and Brain Tumor Imaging with 11C-4DST: A Pilot Study , 2011, The Journal of Nuclear Medicine.

[29]  K. Ishiwata,et al.  Synthesis and radiation dosimetry of 4-borono-2-[18F]fluoro-D,L-phenylalanine: a target compound for PET and boron neutron capture therapy. , 1991, International journal of radiation applications and instrumentation. Part A, Applied radiation and isotopes.

[30]  Kiichi Ishiwata,et al.  In vivo evaluation of [11C]SA4503 as a PET ligand for mapping CNS sigma1 receptors , 2000 .

[31]  H Orihara,et al.  Performance evaluation of a large axial field-of-view PET scanner: SET-2400W , 1997, Annals of nuclear medicine.

[32]  M. Senda,et al.  Electrophilic synthesis of 6-[18F]fluoro-L-DOPA : use of 4-O-pivaloyl-L-DOPA as a suitable precursor for routine production , 1993 .