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Small Animal Molecular Imaging Through μPET and μSPECT

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PET and SPECT of Neurobiological Systems

Abstract

Compared to techniques such as autoradiography and microscopy, the possibility to longitudinally study small animals in vivo justifies the need for preclinical molecular imaging: μSPECT and μPET. In the first part of this chapter, we describe a performance evaluation to compare the three most widespread state-of-the-art μSPECT systems. Once the optimal system is chosen, we use it to study neuromodulation in rats as an application of high-resolution μSPECT imaging. Both the neurobiological effects of deep brain stimulation and transcranial magnetic stimulation are visualized in vivo in healthy animals. In the second part of this chapter, μPET is discussed. We first describe how a preclinical acquisition protocol can be standardized and how the resulting reconstructed images can be accurately quantified. Next, we apply this standardized protocol to a typical application of μPET in drug design, where we study the potency of a mGluR2/3 agonist in an animal model of schizophrenia.

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References

  • Barker AT, Jalinous R, Freeston IL (1985) Non-invasive magnetic stimulation of human motor cortex. The Lancet 1(8437):1106–1107

    Article  CAS  Google Scholar 

  • Beekman F, Have F (2006) The pinhole: gateway to ultra-high-resolution three-dimensional radionuclide imaging. Eur J Nucl Med Mol Imaging 34(2):151–161

    Article  Google Scholar 

  • Benabid AL, Chabardes S, Mitrofanis J, Pollak P (2009) Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. Lancet neurology 8(1):67–81

    Article  PubMed  Google Scholar 

  • Cherry SR (2006) The 2006 Henry N. Wagner Lecture: of mice and men (and Positrons)—advances in PET imaging technology. J Nucl Med 47(11):1735–1745

    Google Scholar 

  • Cilia R, Marotta G, Landi A, Isaias IU, Mariani CB, Vergani F, Benti R, Sganzerla E, Pezzoli G, Antonini A (2008) Clinical and cerebral activity changes induced by subthalamic nucleus stimulation in advanced Parkinson’s disease: a prospective case–control study. Clin Neurol Neurosurg 111(2):140–146

    Article  PubMed  Google Scholar 

  • Dandekar M, Tseng JR, Gambhir SS (2007) Reproducibility of 18F-FDG microPET studies in mouse tumor xenografts. J Nucl Med 48(4):602–607

    Article  PubMed  Google Scholar 

  • De Geeter N, Crevecoeur G, Dupre L (2011) An efficient 3-D eddy-current solver using an independent impedance method for transcranial magnetic stimulation. IEEE Trans Biomed Eng 58(2):310–320

    Article  PubMed  Google Scholar 

  • Dedeurwaerdere S, Wintmolders C, Straetemans R, Pemberton D, Langlois X (2010) Memantine-induced brain activation as a model for the rapid screening of potential novel antipsychotic compounds: exemplified by activity of an mGlu2/3 receptor agonist. Psychopharmacology (Berl) 214(2):505–514

    Article  Google Scholar 

  • Duncan GE, Leipzig JN, Mailman RB, Lieberman JA (1998) Differential effects of clozapine and haloperidol on ketamine-induced brain metabolic activation. Brain Res 812(1):65–75

    Article  CAS  PubMed  Google Scholar 

  • Fueger BJ, Czernin J, Hildebrandt I, Tran C, Halpern BS, Stout D, Phelps ME, Weber WA (2006) Impact of animal handling on the results of 18F-FDG PET studies in mice. J Nucl Med 47(6):999–1006

    CAS  PubMed  Google Scholar 

  • Funke K, Benali A (2011) Modulation of cortical inhibition by rTMS-findings obtained from animal models. J Physiol 589(18):4423–4435

    CAS  PubMed  Google Scholar 

  • Gilling KE, Jatzke C, Hechenberger M, Parsons CG (2009) Potency, voltage-dependency, agonist concentration-dependency, blocking kinetics and partial untrapping of the uncompetitive N-methyl-D-aspartate (NMDA) channel blocker memantine at human NMDA (GluN1/GluN2A) receptors. Neuropharmacology 56(5):866–875

    Article  CAS  PubMed  Google Scholar 

  • Goorden MC, Beekman FJ (2010) High-resolution tomography of positron emitters with clustered pinhole SPECT. Phys Med Biol 55(5):1265–1277

    Article  PubMed  Google Scholar 

  • Hadi M, Bacharach SL, Whatley M, Libutti SK, Straus SE, Rao VK, Wesley R, Carrasquillo JA (2008) Glucose and insulin variations in patients during the time course of a FDG-PET study and implications for the ‘glucose-corrected’ SUV. Nucl Med Biol 35(4):441–445

    Article  CAS  PubMed  Google Scholar 

  • Hayashi T, Ohnishi T, Okabe S, Teramoto N, Nonaka Y, Watabe H, Imabayashi E, Ohta Y, Jino H, Ejima N, Sawada T, Iida H, Matsuda H, Ugawa Y (2004) Long-term effect of motor cortical repetitive transcranial magnetic stimulation [correction]. Ann Neurol 56(1):77–85

    Article  PubMed  Google Scholar 

  • Hildebrandt IJ, Su H, Weber WA (2008) Anesthesia and other considerations for in vivo imaging of small animals. ILAR J 49(1):17–26

    Article  CAS  PubMed  Google Scholar 

  • Homayoun H, Moghaddam B (2007) NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci 27(43):11496–11500

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Inubushi M, Jordan MC, Roos KP, Ross RS, Chatziioannou AF, Stout DB, Dahlbom M, Schelbert HR (2004) Nitrogen-13 ammonia cardiac positron emission tomography in mice: effects of clonidine-induced changes in cardiac work on myocardial perfusion. Eur J Nucl Med Mol Imaging 31(1):110–116

    Article  PubMed  Google Scholar 

  • Jan S, Boisgard R, Fontyn Y, Eroukhmanoff C, Comtat C, Trebossen R (2004) Accuracy and variability of quantitative values obtained for mouse imaging using the microPET FOCUS. Presented at the nuclear science symposium conference record, 2004 IEEE, Rome, Italy, vol 5

    Google Scholar 

  • Katsakiori PF, Kefalopoulou Z, Markaki E, Paschali A, Ellul J, Kagadis GC, Chroni E, Constantoyannis C (2009) Deep brain stimulation for secondary dystonia: results in 8 patients. Acta Neurochir 151(5):473–478, discussion 478

    Article  CAS  PubMed  Google Scholar 

  • Kefalopoulou Z, Paschali A, Markaki E, Vassilakos P, Ellul J, Constantoyannis C (2009) A double-blind study on a patient with tardive dyskinesia treated with pallidal deep brain stimulation. Acta neurologica Scandinavica 119(4):269–273

    Article  CAS  PubMed  Google Scholar 

  • Kim Y-W, Scarpace PJ (2003) Repeated fasting/refeeding elevates plasma leptin without increasing fat mass in rats. Physiol Behav 78(3):459–464

    Article  CAS  PubMed  Google Scholar 

  • Kim H, Furenlid LR, Crawford MJ, Wilson DW, Barber HB, Peterson TE, Hunter WCJ, Liu Z, Woolfenden JM, Barrett HH (2006) SemiSPECT: a small-animal single-photon emission computed tomography (SPECT) imager based on eight cadmium zinc telluride (CZT) detector arrays. Med Phys 33(2):465

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Knol RJJ, De Bruin K, Van Eck-Smit BLF, Pimlott S, Wyper DJ, Booij J (2009) In vivo [(123)I]CNS-1261 binding to D-serine-activated and MK801-blocked NMDA receptors: a storage phosphor imaging study in rats. Synapse 63(7):557–564

    Article  CAS  PubMed  Google Scholar 

  • Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB, Charney DS (1994) Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 51(3):199–214

    Article  CAS  PubMed  Google Scholar 

  • Kwan P, Brodie MJ (2000) Early identification of refractory epilepsy. N Engl J Med 342(5):314–319

    Article  CAS  PubMed  Google Scholar 

  • Lackas C, Schramm NU, Hoppin JW, Engeland U, Wirrwar A, Halling H (2005) T-SPECT: a novel imaging technique for small animal research. IEEE Trans Nucl Sci 52(1):181–187

    Article  Google Scholar 

  • Lancelot S, Zimmer L (2010) Small-animal positron emission tomography as a tool for neuropharmacology. Trends Pharmacol Sci 31(9):411–417

    Article  CAS  PubMed  Google Scholar 

  • Lee K-H, Ko B-H, Paik J-Y, Jung K-H, Choe YS, Choi Y, Kim B-T (2005) Effects of anesthetic agents and fasting duration on 18F-FDG biodistribution and insulin levels in tumor-bearing mice. J Nucl Med 46(9):1531–1536

    CAS  PubMed  Google Scholar 

  • Li Z, Conti PS (2010) Radiopharmaceutical chemistry for positron emission tomography. Adv Drug Deliv Rev 62(11):1031–1051

    Article  CAS  PubMed  Google Scholar 

  • Manook A, Yousefi BH, Willuweit A, Platzer S, Reder S, Voss A, Huisman M, Settles M, Neff F, Velden J, Schoor M, von der Kammer H, Wester H-J, Schwaiger M, Henriksen G, Drzezga A (2012) Small-animal PET imaging of amyloid-beta plaques with [11C]PiB and its multi-modal validation in an APP/PS1 mouse model of Alzheimer’s disease. PLoS ONE 7(3):e31310

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Marsteller DA, Barbarich-Marsteller NC, Fowler JS, Schiffer WK, Alexoff DL, Rubins DJ, Dewey SL (2006) Reproducibility of intraperitoneal 2-deoxy-2-[18F]-fluoro-d-glucose cerebral uptake in rodents through time. Nucl Med Biol 33(1):71–79

    Article  CAS  PubMed  Google Scholar 

  • Martic-Kehl MI, Ametamey SM, Alf MF, Schubiger PA, Honer M (2012) Impact of inherent variability and experimental parameters on the reliability of small animal PET data. EJNMMI Research 2(1):26

    Article  PubMed Central  PubMed  Google Scholar 

  • Matsuda H, Tsuji S, Shuke N, Sumiya H, Tonami N, Hisada K (1993) Noninvasive measurements of regional cerebral blood flow using technetium-99m hexamethylpropylene amine oxime. Eur J Nucl Med 20(5):391–401

    Article  CAS  PubMed  Google Scholar 

  • McElroy DP, MacDonald LR, Beekman FJ, Wang YC, Patt BE, Iwanczyk JS, Tsui BMW, Hoffman EJ (2002) Performance evaluation of A-SPECT: A high resolution desktop pinhole SPECT system for imaging small animals. IEEE Transactions on Nuclear Science 49(5):2139–2147. doi:10.1109/TNS.2002.803801

    Google Scholar 

  • Meijer MK, Lemmens AG, Van Zutphen BFM, Baumans V (2005) Urinary corticosterone levels in mice in response to intraperitoneal injections with saline. J Appl Anim Welf Sci 8(4):279–283

    Article  CAS  PubMed  Google Scholar 

  • Mok GSP, Yu J, Du Y, Wang Y, Tsui BMW (2011) Evaluation of a multi-pinhole collimator for imaging small animals with different sizes. Mol Imaging Biol 14(1):60–69

    Article  Google Scholar 

  • Nowland MH, Hugunin KMS, Rogers KL (2011) Effects of short-term fasting in male Sprague–Dawley rats. Comp Med 61(2):138–144

    CAS  PubMed  Google Scholar 

  • Ose T, Watabe H, Hayashi T, Kudomi N, Hikake M, Fukuda H, Teramoto N, Watanabe Y, Onoe H, Iida H (2012) Quantification of regional cerebral blood flow in rats using an arteriovenous shunt and micro-PET. Nucl Med Biol 39(5):730–741

    Article  CAS  PubMed  Google Scholar 

  • Patel VD, Lee DE, Alexoff DL, Dewey SL, Schiffer WK (2008) Imaging dopamine release with Positron Emission Tomography (PET) and 11C-raclopride in freely moving animals. Neuroimage 41(3):1051–1066

    Article  PubMed  Google Scholar 

  • Patil ST, Zhang L, Martenyi F, Lowe SL, Jackson KA, Andreev BV, Avedisova AS, Bardenstein LM, Gurovich IY, Morozova MA, Mosolov SN, Neznanov NG, Reznik AM, Smulevich AB, Tochilov VA, Johnson BG, Monn JA, Schoepp DD (2007) Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nature medicine 13(9):1102–1107

    Article  CAS  PubMed  Google Scholar 

  • Ridding M, Rothwell J (2007) Is there a future for therapeutic use of transcranial magnetic stimulation? Nat Rev Neurosci 8(7):559–567

    Article  CAS  PubMed  Google Scholar 

  • Roth B, Saypol J, Hallett M, Cohen L (1991) A theoretical calculation of the electric field induced in the cortex during magnetic stimulation. Electroencephalogr Clin Neurophysiol 81(1):47–56

    Article  CAS  PubMed  Google Scholar 

  • Saab BJ, Maclean AJB, Kanisek M, Zurek AA, Martin LJ, Roder JC, Orser BA (2010) Short-term memory impairment after isoflurane in mice is prevented by the α5 γ-aminobutyric acid type A receptor inverse agonist L-655,708. Anesthesiology 113(5):1061–1071

    Article  CAS  PubMed  Google Scholar 

  • Schiffer WK, Mirrione MM, Dewey SL (2007) Optimizing experimental protocols for quantitative behavioral imaging with 18F-FDG in rodents. J Nucl Med 48(2):277–287

    CAS  PubMed  Google Scholar 

  • Schramm NU, Ebel G, Engeland U, Schurrat T, Behe M, Behr TM (2003) High-resolution SPECT using multipinhole collimation. IEEE Trans Nucl Sci 50(3):315–320

    Article  Google Scholar 

  • Schramm NU, Lackas C, Hoppin JW, Forrer F, de Jong M (2006) The nanoSPECT/CT: a high-sensitivity small-animal SPECT/CT with submillimeter spatial resolution. Eur J Nucl Med Mol Imaging 33:S117

    Google Scholar 

  • Spencer SS (2002) Neural networks in human epilepsy: evidence of and implications for treatment. Epilepsia 43(3):219–227

    Article  PubMed  Google Scholar 

  • Tsai GG, Coyle JTJ (2001) Glutamatergic mechanisms in schizophrenia. Pharmacology and Toxicology 42:165–179

    Google Scholar 

  • van der Have F, Vastenhouw B, Ramakers RM, Branderhorst W, Krah JO, Ji C, Staelens SG, Beekman FJ (2009) U-SPECT-II: an ultra-high-resolution device for molecular small-animal imaging. J Nucl Med 50(4):599–605

    Article  PubMed  Google Scholar 

  • Wahl RL, Henry CA, Ethier SP (1992) Serum glucose: effects on tumor and normal tissue accumulation of 2-[F-18]-fluoro-2-deoxy-D-glucose in rodents with mammary carcinoma. Radiology 183(3):643–647

    CAS  PubMed  Google Scholar 

  • Wong KP, Sha W, Zhang X, Huang SC (2011) Effects of administration route, dietary condition, and blood glucose level on kinetics and uptake of 18F-FDG in mice. J Nucl Med 52(5):800–807

    Article  PubMed Central  PubMed  Google Scholar 

  • Wyckhuys T, Boon P, Raedt R, Van Nieuwenhuyse B, Vonck K, Wadman W (2010) Suppression of hippocampal epileptic seizures in the kainate rat by Poisson distributed stimulation. Epilepsia 51(11):2297–2304

    Article  PubMed  Google Scholar 

  • Wyckhuys T, De Geeter N, Crevecoeur G, Stroobants S, Staelens S (2013) Quantifying the effect of repetitive transcranial magnetic stimulation in the rat brain by μSPECT CBF scans. Brain Stimul 6:554–562

    Article  PubMed  Google Scholar 

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Acknowledgements

We would like to thank our other colleagues from the Molecular Imaging Center Antwerp of Antwerp University, the Cyclotron Radiopharmacy and the Nuclear Medicine Department of the University Hospital Antwerp as well as our partners at Neuroscience Janssen Pharmaceutical companies of Johnson & Johnson and our former colleagues of UGent-Medisip-Infinity.

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Correspondence to Steven Staelens MScEng, PhD .

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Staelens, S., Wyckhuys, T., Deleye, S., Verhaeghe, J., Wyffels, L., Stroobants, S. (2014). Small Animal Molecular Imaging Through μPET and μSPECT. In: Dierckx, R., Otte, A., de Vries, E., van Waarde, A., Luiten, P. (eds) PET and SPECT of Neurobiological Systems. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-42014-6_2

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  • DOI: https://doi.org/10.1007/978-3-642-42014-6_2

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