Abstract
Positron emission tomography (PET) imaging of small animals enables researchers to bridge the gap between in vitro science and in vivo human studies. The imaging paradigm can be established and refined in animals before implementation in humans and image data related to ex vivo assays of biological activity. Small animal PET (saPET) imaging enables assessment of baseline focal pathophysiology, pharmacokinetics, biological target modulation and the efficacy of novel drugs. The potential and challenge of this technology as applied to anticancer drug development is discussed here.
Similar content being viewed by others
References
R Myers (2001) ArticleTitleThe biological application of small animal PET imaging Nucl Med Biol 28 585–593 Occurrence Handle10.1016/S0969-8051(01)00213-X Occurrence Handle1:STN:280:DC%2BD3MvntValtQ%3D%3D Occurrence Handle11516702
SP Hume R Myers (2002) ArticleTitleDedicated small animal scanners: A new tool for drug development Curr Pharm Des 8 1497–1511 Occurrence Handle1:CAS:528:DC%2BD38XkvVWksrs%3D
SP Hume RN Gunn T Jones (1998) ArticleTitlePharmacological constraints associated with positron emission tomographic scanning of small laboratory animals Eur J Nucl Med 25 173–176 Occurrence Handle10.1007/s002590050211 Occurrence Handle1:CAS:528:DyaK1cXhtVWisL4%3D Occurrence Handle9473266
JY Qi RM Leary SR Cherry A Chatziioannou TH Farquhar (1998) ArticleTitleHigh-resolution 3D Bayesian image reconstruction using the micro-PET small-animal scanner Phys Med Biol 43 1001–1013 Occurrence Handle10.1088/0031-9155/43/4/027
RJ Walledge AJ Reader EO Aboagye et al. (2002) ArticleTitle4D PET with the quad-HIDAC: Development of dynamic list-mode EM image reconstruction IEEE Nucl Sci Symp Conf Rec 3 1716–1720 Occurrence Handlefull_text||10.1109/NSSMIC.2002.1239654
DR Collingridge M Glaser S Osman et al. (2003) ArticleTitleIn vitro selectivity, in vivo biodistribution and tumor uptake of annexin V radiolabelled with a positron emitting radioisotope Br J Cancer 89 1327–1333 Occurrence Handle10.1038/sj.bjc.6601262
H Barthel MC Cleij DR Collingridge et al. (2003) ArticleTitle3′-deoxy-3′-[18F]Fluorothymidine as a new marker for monitoring tumor response to antiproliferative therapy in vivo with positron emission tomography Cancer Res 63 3791–3798 Occurrence Handle1:CAS:528:DC%2BD3sXltVGqs78%3D Occurrence Handle12839975
EO Aboagye A Saleem PM Price (2002) Tumor imaging applications in the testing of new drugs BC Baguley DJ Kerr (Eds) Anticancer drug development Academic Press San Diego 353–369
N Gupta P Price EO Aboagye (2002) ArticleTitlePET for in vivo pharmacokinetic and pharmacodynamic measurements Eur J Cancer 38 2094–2107 Occurrence Handle10.1016/S0959-8049(02)00413-6
LA Hammond L Denis U Salman et al. (2003) ArticleTitlePositron emission tomography (PET): Expanding the horizons of oncology drug development Invest New Drugs 21 309–340 Occurrence Handle10.1023/A:1025468611547
EO Aboagye PM Price (2003) ArticleTitleUse of positron emission tomography in anticancer drug development Invest New Drugs 21 169–181 Occurrence Handle10.1023/A:1023521412787
EO Aboagye A Saleem V Cunningham S Osman P Price (2001) ArticleTitleExtraction of 5-fluorouracil by tumor and liver: A non-invasive positron emission tomography study of patients with gastrointestinal cancer Cancer Res 61 4937–4941 Occurrence Handle1:CAS:528:DC%2BD3MXltVeqtLg%3D Occurrence Handle11431319
JR Bading PB Yoo JD Fissekis et al. (2003) ArticleTitleKinetic modeling of 5-fluorouracil anabolism in colorectal adenocarcinoma: A positron emission tomography study in rats Cancer Res 63 3667–3674
S Osman SK Luthra F Brady et al. (1997) ArticleTitleStudies on the metabolism of the novel antitumor agent [N-methyl-11C]N-[2-(dimethylamino)ethyl]acridine-4-carboxamide in rats and humans prior to phase I clinical trials Cancer Res 57 2172–2180
A Saleem J Yap S Osman et al. (2000) ArticleTitleModulation of fluorouracil tissue pharmacokinetics by eniluracil: In-vivo imaging of drug action Lancet 355 2125–2131 Occurrence Handle10.1016/S0140-6736(00)02380-1 Occurrence Handle1:CAS:528:DC%2BD3cXkvVWjtrk%3D Occurrence Handle10902627
A Saleem RJ Harte JC Matthews et al. (2001) ArticleTitlePharmacokinetic evaluation of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA; XR5000) in patients by positron emission tomography J Clin Oncol 19 1421–1429
OT DeJesus D Murali LG Flores et al. (2003) ArticleTitleSynthesis of [F-18]-ZD1839 as a PET imaging agent for epidermal growth factor receptors J Label Compd Radiopharm 46 S1 Occurrence Handle10.1002/jlcr.750
S Osman G Rowlinson-Busza SK Luthra et al. (2001) ArticleTitleComparative biodistribution and metabolism of carbon-11-radiolabeled N-[2-(dimethylamino)ethyl] acridine-4-carboxamide and DNA-interacting analogs Cancer Res 61 2935–2944
K Spaepen S Stroobants P Dupont et al. (2003) ArticleTitle[(18)F]FDG PET monitoring of tumor response to chemotherapy: Does [(18)F]FDG uptake correlate with the viable tumor cell fraction? Eur J Nucl Med Mol Imaging 30 682–688
HL Anderson JT Yap MP Miller et al. (2003) ArticleTitleAssessment of pharmacodynamic vascular response in a phase I trial of combretastatin A4 phosphate J Clin Oncol 21 2823–2830 Occurrence Handle10.1200/JCO.2003.05.186
L Bentzen S Keiding MR Horsman et al. (2000) ArticleTitleFeasibility of detecting hypoxia in experimental mouse tumors with 18F-fluorinated tracers and positron emission tomography—a study evaluating [18F]fluoro-2-deoxy-D-glucose Acta Oncol 39 629–637 Occurrence Handle10.1080/028418600750013320 Occurrence Handle1:STN:280:DC%2BD3M%2Fkt12ltg%3D%3D Occurrence Handle11093372
JS Rasey PD Hofstrand LK Chin TJ Tewson (1999) ArticleTitleCharacterization of [18F]fluoroetanidazole, a new radiopharmaceutical for detecting tumor hypoxia J Nucl Med 40 1072–1079 Occurrence Handle1:CAS:528:DyaK1MXktVaqsLk%3D Occurrence Handle10452326
M Glaser DR Collingridge EO Aboagye et al. (2003) ArticleTitleIodine-124 labelled annexin-V as a potential radiotracer to study apoptosis using positron emission tomography Appl Radiat Isotopes 58 55–62 Occurrence Handle10.1016/S0969-8043(02)00239-7
DR Collingridge VA Carroll M Glaser et al. (2002) ArticleTitleThe development of [124I]iodinated-VG76e: A novel tracer for imaging vascular endothelial growth factor in vivo using positron emission tomography Cancer Res 62 5912–5919 Occurrence Handle1:CAS:528:DC%2BD38XotFyktLo%3D Occurrence Handle12384557
R Haubner HJ Wester WA Weber et al. (2001) ArticleTitleNoninvasive imaging of alpha(v)beta3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography Cancer Res 61 1781–1785 Occurrence Handle1:CAS:528:DC%2BD3MXit1Ohtbk%3D Occurrence Handle11280722
T Groot-Wassink EO Aboagye M Glaser NR Lemoine G Vassaux (2002) ArticleTitleAdenovirus biodistribution and noninvasive imaging of gene expression in vivo by positron emission tomography using human sodium/iodide symporter as reporter gene Hum Gene Ther 13 1723–1735 Occurrence Handle10.1089/104303402760293565 Occurrence Handle1:CAS:528:DC%2BD38XntlCqsLc%3D Occurrence Handle12396625
SS Gambhir JR Barrio HR Herschman ME Phelps (1999) ArticleTitleAssays for noninvasive imaging of reporter gene expression Nucl Med Biol 26 481–490 Occurrence Handle10.1016/S0969-8051(99)00021-9
D Liu OC Hutchinson S Osman et al. (2002) ArticleTitleUse of radiolabelled choline as a pharmacodynamic marker for the signal transduction inhibitor geldanamycin Br J Cancer 87 783–789 Occurrence Handle10.1038/sj.bjc.6600558
L Aloj C Caracó E Jagoda WC Eckelman RD Neumann (1999) ArticleTitleGlut-1 and hexokinase expression: Relationship with 2-fluoro-2-deoxy-D-glucose uptake in A431 and T47D cells in culture Cancer Res 59 4709–4714
J Boren M Cascante S Marin et al. (2001) ArticleTitleGleevec (3STI571) influences metabolic enzyme activities and glucose carbon flow towards nucleic acid and fatty acid synthesis in myeloid tumor cells J Biol Chem 276 37747–37753
JL Sherley TJ Kelly (1988) ArticleTitleRegulation of human thymidine kinase during the cell cycle J Biol Chem 263 8350–8358 Occurrence Handle1:CAS:528:DyaL1cXkt1SqsLs%3D Occurrence Handle3372530
JS Rasey JR Grierson LW Wiens PD Kolb JL Schwartz (2002) ArticleTitleValidation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells J Nucl Med 43 1210–1217 Occurrence Handle1:CAS:528:DC%2BD38Xns1elsrk%3D Occurrence Handle12215561
J Toyohara A Waki S Takamatsu et al. (2002) ArticleTitleBasis of FLT as a cell proliferation marker: Comparative uptake studies with [3H]arabinothymidine, and cell-analysis in 22 asynchronously growing tumor cell lines Nucl Med Biol 29 281–287 Occurrence Handle10.1016/S0969-8051(02)00286-X Occurrence Handle11929696
AJ Fischman AA Bonab E Livni et al. (2003) ArticleTitleEvaluation of a novel CDK2 inhibitor by microPET: A comparative study of FDG and FLT Mol Imaging Biol 5 157
VJ Lowe JN Sarkaria BJ Kemp SM Geyer CD James (2003) ArticleTitleEvaluation of EGFR therapy by FLT PET/CT imaging Mol Imaging Biol 5 160
SJ Martin CP Reutelingsperger AJ McGahon et al. (1995) ArticleTitleEarly redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: Inhibition by overexpression of Bcl-2 and Abl J Exp Med 182 1545–1556 Occurrence Handle10.1084/jem.182.5.1545 Occurrence Handle1:CAS:528:DyaK2MXovFWqsL4%3D Occurrence Handle7595224
FG Blakenberg J Tait K Ohtsuki HW Strauss (2000) ArticleTitleApoptosis: The importance of nuclear medicine Nucl Med Commun 21 241–250 Occurrence Handle10.1097/00006231-200003000-00008
Acknowledgment
EOA’s laboratory is funded by UK Medical Research Council, Wellcome Trust, U.S. Army Medical Research and Material Command and Cancer Research UK.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Aboagye, E.O. Positron Emission Tomography Imaging of Small Animals in Anticancer Drug Development. Mol Imaging Biol 7, 53–58 (2005). https://doi.org/10.1007/s11307-005-0886-2
Issue Date:
DOI: https://doi.org/10.1007/s11307-005-0886-2