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EJNMMI Research
Published in: EJNMMI Research 1/2013

Open Access 01-12-2013 | Original research

Multimodality imaging using SPECT/CT and MRI and ligand functionalized 99mTc-labeled magnetic microbubbles

Authors: Åsa A Barrefelt, Torkel B Brismar, Gabriella Egri, Peter Aspelin, Annie Olsson, Letizia Oddo, Silvia Margheritelli, Kenneth Caidahl, Gaio Paradossi, Lars Dähne, Rimma Axelsson, Moustapha Hassan

Published in: EJNMMI Research | Issue 1/2013

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Abstract

Background

In the present study, we used multimodal imaging to investigate biodistribution in rats after intravenous administration of a new 99mTc-labeled delivery system consisting of polymer-shelled microbubbles (MBs) functionalized with diethylenetriaminepentaacetic acid (DTPA), thiolated poly(methacrylic acid) (PMAA), chitosan, 1,4,7-triacyclononane-1,4,7-triacetic acid (NOTA), NOTA-super paramagnetic iron oxide nanoparticles (SPION), or DTPA-SPION.

Methods

Examinations utilizing planar dynamic scintigraphy and hybrid imaging were performed using a commercially available single-photon emission computed tomography (SPECT)/computed tomography (CT) system. For SPION containing MBs, the biodistribution pattern of 99mTc-labeled NOTA-SPION and DTPA-SPION MBs was investigated and co-registered using fusion SPECT/CT and magnetic resonance imaging (MRI). Moreover, to evaluate the biodistribution, organs were removed and radioactivity was measured and calculated as percentage of injected dose.

Results

SPECT/CT and MRI showed that the distribution of 99mTc-labeled ligand-functionalized MBs varied with the type of ligand as well as with the presence of SPION. The highest uptake was observed in the lungs 1 h post injection of 99mTc-labeled DTPA and chitosan MBs, while a similar distribution to the lungs and the liver was seen after the administration of PMAA MBs. The highest counts of 99mTc-labeled NOTA-SPION and DTPA-SPION MBs were observed in the lungs, liver, and kidneys 1 h post injection. The highest counts were observed in the liver, spleen, and kidneys as confirmed by MRI 24 h post injection. Furthermore, the results obtained from organ measurements were in good agreement with those obtained from SPECT/CT.

Conclusions

In conclusion, microbubbles functionalized by different ligands can be labeled with radiotracers and utilized for SPECT/CT imaging, while the incorporation of SPION in MB shells enables imaging using MR. Our investigation revealed that biodistribution may be modified using different ligands. Furthermore, using a single contrast agent with fusion SPECT/CT/MR multimodal imaging enables visualization of functional and anatomical information in one image, thus improving the diagnostic benefit for patients.
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Literature
1.
Brismar TB, Grishenkov D, Gustafsson B, Harmark J, Barrefelt A, Kothapalli SV, Margheritelli S, Oddo L, Caidahl K, Hebert H, Paradossi G: Magnetite nanoparticles can be coupled to microbubbles to support multimodal imaging. Biomacromolecules 2012, 13: 1390–1399. 10.1021/bm300099fCrossRefPubMed
2.
Heneweer C, Gendy SE, Penate-Medina O: Liposomes and inorganic nanoparticles for drug delivery and cancer imaging. Ther Deliv 2012, 3: 645–566. 10.4155/tde.12.38CrossRefPubMed
3.
Howles GP, Qi Y, Rosenzweig SJ: Nightingale KR. Johnson GA: Functional neuroimaging using ultrasonic blood–brain barrier disruption and manganese-enhanced MRI. J Vis Exp; 2012. 10.3791/4055
4.
Lazarova N, Causey PW, Lemon JA, Czorny SK, Forbes JR, Zlitni A, Genady A, Foster FS, Valliant JF: The synthesis, magnetic purification and evaluation of 99m Tc-labeled microbubbles. Nucl Med Biol 2011, 38: 1111–1118. 10.1016/j.nucmedbio.2011.04.008CrossRefPubMed
5.
Moestue SA, Gribbestad IS, Hansen R: Intravascular targets for molecular contrast-enhanced ultrasound imaging. Int J Mol Sci 2012, 13: 6679–6697. 10.3390/ijms13066679CrossRefPubMed
6.
Cai X, Yang F, Gu N: Applications of magnetic microbubbles for theranostics. Theranostics 2012, 2: 103–112. 10.7150/thno.3464CrossRefPubMed
7.
Madru R, Kjellman P, Olsson F, Wingardh K, Ingvar C, Stahlberg F, Olsrud J, Lätt J, Fredriksson S, Knutsson L, Strand SE: 99m Tc-labeled superparamagnetic iron oxide nanoparticles for multimodality SPECT/MRI of sentinel lymph nodes. J Nucl Med 2012, 53: 459–463. 10.2967/jnumed.111.092437CrossRefPubMed
8.
Unnikrishnan S, Klibanov AL: Microbubbles as ultrasound contrast agents for molecular imaging: preparation and application. AJR Am J Roentgenol 2012, 199: 292–299. 10.2214/AJR.12.8826CrossRefPubMed
9.
Misri R, Saatchi K, Hafeli UO: Nanoprobes for hybrid SPECT/MR molecular imaging. Nanomedicine (Lond) 2012, 7: 719–733. 10.2217/nnm.12.32CrossRef
10.
Wells DJ: Animal welfare and the 3Rs in European biomedical research. Ann N Y Acad Sci 2011, 1245: 14–16. 10.1111/j.1749-6632.2011.06335.xCrossRefPubMed
11.
Cavalieri F, Chiessi E, Villa R, Vigano L, Zaffaroni N, Telling MF, Paradossi G: Novel PVA-based hydrogel microparticles for doxorubicin delivery. Biomacromolecules 2008, 9: 1967–1973. 10.1021/bm800225vCrossRefPubMed
12.
Cerroni B, Chiessi E, Margheritelli S, Oddo L, Paradossi G: Polymer shelled microparticles for a targeted doxorubicin delivery in cancer therapy. Biomacromolecules 2011, 12: 593–601. 10.1021/bm101207kCrossRefPubMed
13.
Ghugare SV, Mozetic P, Paradossi G: Temperature-sensitive poly(vinyl alcohol)/poly(methacrylate-co- N -isopropyl acrylamide) microgels for doxorubicin delivery. Biomacromolecules 2009, 10: 1589–1596. 10.1021/bm900185uCrossRefPubMed
14.
Li S, Goins B, Zhang L, Bao A: Novel multifunctional theranostic liposome drug delivery system: construction, characterization, and multimodality MR, near-infrared fluorescent, and nuclear imaging. Bioconjug Chem 2012, 23: 1322–1332. 10.1021/bc300175dCrossRefPubMed
15.
Gomes CM, Abrunhosa AJ, Ramos P, Pauwels EK: Molecular imaging with SPECT as a tool for drug development. Adv Drug Deliv Rev 2011, 63: 547–554. 10.1016/j.addr.2010.09.015CrossRefPubMed
16.
Accorsi R: Brain single-photon emission CT physics principles. AJNR Am J Neuroradiol 2008, 29: 1247–1256. 10.3174/ajnr.A1175CrossRefPubMed
17.
Chowdhury FU, Scarsbrook AF: The role of hybrid SPECT-CT in oncology: current and emerging clinical applications. Clin Radiol 2008, 63: 241–251. 10.1016/j.crad.2007.11.008CrossRefPubMed
18.
Jaszczak RJ: The early years of single photon emission computed tomography (SPECT): an anthology of selected reminiscences. Phys Med Biol 2006, 51: R99-R115. 10.1088/0031-9155/51/13/R07CrossRefPubMed
19.
Jaszczak RJ, Coleman RE: Single photon emission computed tomography (SPECT): principles and instrumentation. Invest Radiol 1985, 20: 897–910. 10.1097/00004424-198512000-00004CrossRefPubMed
20.
Patton JA, Turkington TG: SPECT/CT physical principles and attenuation correction. J Nucl Med Technol 2008, 36: 1–10. 10.2967/jnmt.107.046839CrossRefPubMed
21.
Mariani G, Bruselli L, Kuwert T, Kim EE, Flotats A, Israel O, Dondi M, Watanabe N: A review on the clinical uses of SPECT/CT. Eur J Nucl Med Mol Imaging 2010, 37: 1959–1985. 10.1007/s00259-010-1390-8CrossRefPubMed
22.
Hauser W, Atkins HL, Nelson KG, Richards P: Technetium-99m DTPA: a new radiopharmaceutical for brain and kidney scanning. Radiology 1970, 94: 679–684.CrossRefPubMed
23.
Cavalieri F, El Hamassi A, Chiessi E, Paradossi G, Villa R, Zaffaroni N: Tethering functional ligands onto shell of ultrasound active polymeric microbubbles. Biomacromolecules 2006, 7: 604–611. 10.1021/bm050723gCrossRefPubMed
24.
Koping-Hoggard M, Varum KM, Issa M, Danielsen S, Christensen BE, Stokke BT, Artursson P: Improved chitosan-mediated gene delivery based on easily dissociated chitosan polyplexes of highly defined chitosan oligomers. Gene Ther 2004, 11: 1441–1452. 10.1038/sj.gt.3302312CrossRefPubMed
25.
Wen YZ, Liu WQ, Fang ZH, Liu WP: Effects of adsorption interferents on removal of Reactive Red 195 dye in wastewater by chitosan. J Environ Sci (China) 2005, 17: 766–769.
26.
Eisenwiener KP, Prata MI, Buschmann I, Zhang HW, Santos AC, Wenger S, Reubi JC, Mäcke HR: NODAGATOC, a new chelator-coupled somatostatin analogue labeled with [ 67/68 Ga] and [ 111 In] for SPECT, PET, and targeted therapeutic applications of somatostatin receptor (hsst2) expressing tumors. Bioconjug Chem 2002, 13: 530–541. 10.1021/bc010074fCrossRefPubMed
27.
Cavalieri F, Zhou M, Caruso F, Ashokkumar M: One-pot ultrasonic synthesis of multifunctional microbubbles and microcapsules using synthetic thiolated macromolecules. Chem Commun (Camb) 2011, 47: 4096–4098. 10.1039/c0cc05095dCrossRef
28.
Liu B, Yan E, Zhang X, Yang X, Bai F: A general method for the synthesis of monodisperse hollow inorganic–organic hybrid microspheres with interior functionalized poly(methacrylic acid) shells. J Colloid Interface Sci 2012, 369: 144–153. 10.1016/j.jcis.2011.12.029CrossRefPubMed
29.
Cavalieri F, El Hamassi A, Chiessi E, Paradossi G: Stable polymeric microballoons as multifunctional device for biomedical uses: synthesis and characterization. Langmuir 2005, 21: 8758–8764. 10.1021/la050287jCrossRefPubMed
30.
Peyratout CS, Dahne L: Tailor-made polyelectrolyte microcapsules: from multilayers to smart containers. Angew Chem 2004, 43: 3762–3783. 10.1002/anie.200300568CrossRef
31.
Shim KM, Kim SE, Moon C, Kim SH, Bae CS, Han HJ, Kang SS: A detailed examination of pulmonary uptake of (99m)Tc-tin colloid in healthy mature miniature pigs. In Vivo 2009, 23: 551–554.PubMed
32.
Council of Europe, Convention on the Elaboration of a European Pharmacopoeia: The European pharmacopoeia. Fortschr Med 1980, 98: 150.
33.
Chen CC, Sirsi SR, Homma S, Borden MA: Effect of surface architecture on in vivo ultrasound contrast persistence of targeted size-selected microbubbles. Ultrasound Med Biol 2012, 38: 492–503. 10.1016/j.ultrasmedbio.2011.12.007CrossRefPubMed
34.
Yu T, Hubbard D, Ray A, Ghandehari H: In vivo biodistribution and pharmacokinetics of silica nanoparticles as a function of geometry, porosity and surface characteristics. J Control Release 2012,163(1):46–54. 10.1016/j.jconrel.2012.05.046CrossRefPubMed
35.
Lartigue L, Wilhelm C, Servais J, Factor C, Dencausse A, Bacri JC, Luciani N, Gazeau F: Nanomagnetic sensing of blood plasma protein interactions with iron oxide nanoparticles: impact on macrophage uptake. ACS Nan 2012, 6: 2665–2678. 10.1021/nn300060uCrossRef
36.
Lesniak A, Fenaroli F, Monopoli MP, Aberg C, Dawson KA, Salvati A: Effects of the presence or absence of a protein corona on silica nanoparticle uptake and impact on cells. ACS Nano 2012, 6: 5845–5857. 10.1021/nn300223wCrossRefPubMed
Metadata
Title
Multimodality imaging using SPECT/CT and MRI and ligand functionalized 99mTc-labeled magnetic microbubbles
Authors
Åsa A Barrefelt
Torkel B Brismar
Gabriella Egri
Peter Aspelin
Annie Olsson
Letizia Oddo
Silvia Margheritelli
Kenneth Caidahl
Gaio Paradossi
Lars Dähne
Rimma Axelsson
Moustapha Hassan
Publication date
01-12-2013
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2013
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/2191-219X-3-12

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