Abstract
Ultrasound is a rapidly advancing field with many emerging diagnostic and therapeutic applications. For diagnostics, new vascular targets are routinely identified and mature technologies are being translated to humans, while other recent innovations may bring about the creation of acoustic reporter genes and micron-scale resolution with ultrasound. As a cancer therapy, ultrasound is being explored as an adjuvant to immune therapies and to deliver acoustically or thermally active drugs to tumor regions. Ultrasound-enhanced delivery across the blood brain barrier (BBB) could potentially be very impactful for brain cancers and neurodegenerative diseases where the BBB often impedes the delivery of therapeutic molecules. In this minireview, we provide an overview of these topics in the field of ultrasound that are especially relevant to the interests of World Molecular Imaging Society.
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References
Hu X, Caskey C, Mahakian L et al (2012) In vivo validation and 3D visualization of broadband ultrasound molecular imaging. Am J Nucl Med Mol Imaging 3:336–349
Korpanty G, Carbon JG, Grayburn PA et al (2007) Monitoring response to anticancer therapy by targeting microbubbles to tumor vasculature. Clin Cancer Res 13:323–330
Ellegala DB, Leong-Poi H, Carpenter JE et al (2003) Imaging tumor angiogenesis with contrast ultrasound and microbubbles targeted to αvβ3. Circulation 108:336–341
Sanna V, Pintus G, Bandiera P et al (2011) Development of polymeric microbubbles targeted to prostate-specific membrane antigen as prototype of novel ultrasound contrast agents. Mol Pharmac 8:748–757
Bachmann C, Klibanov AL, Olson TS et al (2006) Targeting mucosal addressin cellular adhesion molecule (MAdCAM)-1 to noninvasively image experimental Crohn’s disease. Gastroenterology 130:8–16
Kaufmann BA, Lewis C, Xie A et al (2007) Detection of recent myocardial ischaemia by molecular imaging of P-selectin with targeted contrast echocardiography. Eur Heart J 28:2011–2017
Khanicheh E, Qi Y, Xie A et al (2013) Molecular imaging reveals rapid reduction of endothelial activation in early atherosclerosis with apocynin independent of antioxidative properties. Arterioscl Thromb Vasc Biol 33:2187–2192
Abou-Elkacem L, Bachawa SV, Willmann JK (2015) Ultrasound molecular imaging: moving toward clinical translation. Eur J Radiol 84:1685–1693
Willmann JK, Testa A, Rinaldi P et al (2017) Ultrasound molecular imaging in patients with breast and ovarian lesions: first-in-human results. J Clin Oncol, In press 2017
Jackson A, Castle JW, Smith A, Kalli CK (2016) Optison™ albumin microspheres in ultrasound-assisted gene therapy and drug delivery. In Albumin in medicine, ed: Springer, pp. 121–145
Cavalieri F, Finelli I, Tortora M et al (2008) Polymer microbubbles as diagnostic and therapeutic gas delivery device. Chem Mater 20:3254–3258
Lakshmanan A, Farhadi A, Nety SP et al (2016) Molecular engineering of acoustic protein nanostructures. ACS Nano 10:7314–7322
Shapiro MG, Goodwill PW, Neogy A et al (2014) Biogenic gas nanostructures as ultrasonic molecular reporters. Nature Nanotechnol 9:311–316
O'Reilly MS, Hynynen K (2013) A super-resolution ultrasound method for brain vascular mapping. Med Phys 40:110701
Desailly Y, Couture O, Fink M, Tanter M (2013) Sono-activated ultrasound localization microscopy. Appl Phys Letters 103:174107
Errico C, Pierre J, Pezet S et al (2015) Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging. Nature 527:499–502
Foiret J, Zhang H, Mahakian L, et al. (2016) Super-localization of contrast agents in moving organs, first experiments in a rat kidney. In Ultrasonics Symposium (IUS), 2016 I.E. International, 2016, pp. 1–4
Kennedy J, Ter Haar G, Cranston D (2014) High intensity focused ultrasound: surgery of the future? Br J Radiol. doi:10.1259/bjr/17150274
Chapman A, ter Haar G (2007) Thermal ablation of uterine fibroids using MR-guided focused ultrasound-a truly non-invasive treatment modality. Eur Radiol 17:2505–2511
Li C, Zhang W, Fan W et al (2010) Noninvasive treatment of malignant bone tumors using high-intensity focused ultrasound. Cancer 116:3934–3942
Fischer K, Gedroyc W, Jolesz FA (2010) Focused ultrasound as a local therapy for liver cancer. Cancer J 16:118–124
Yudina A, Lepetit-Coiffé M, Moonen CT (2011) Evaluation of the temporal window for drug delivery following ultrasound-mediated membrane permeability enhancement. Mol Imaging Biol 13:239–249
Rapoport N, Gupta R, Kim Y-S, O'Neill BE (2015) Polymeric micelles and nanoemulsions as tumor-targeted drug carriers: insight through intravital imaging. J Control Release 206:153–160
Wang T-Y, Choe JW, Pu K et al (2015) Ultrasound-guided delivery of microRNA loaded nanoparticles into cancer. J Control Release 203:99–108
Needham D, Anyarambhatla G, Kong G, Dewhirst MW (2000) A new temperature-sensitive liposome for use with mild hyperthermia: characterization and testing in a human tumor xenograft model. Cancer Res 60:1197–1201
Kheirolomoom A, Lai C-Y, Tam SM et al (2013) Complete regression of local cancer using temperature-sensitive liposomes combined with ultrasound-mediated hyperthermia. J Control Release 172:266–273
Silvestrini MT, Kheirolomoom A, Ingham ES et al (2016) Abstract LB-052: activatable nanodelivery combined with CpG-ODN and anti-PD-1 achieves a complete response in directly-treated and contralateral tumors in a murine breast cancer model. Cancer Res 76:LB-052-LB-052
Kotopoulis S, Delalande A, Popa M et al (2014) Sonoporation-enhanced chemotherapy significantly reduces primary tumour burden in an orthotopic pancreatic cancer xenograft. Mol Imaging Biol 16:53–62
Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA (2001) Noninvasive MR imaging–guided focal opening of the blood-brain barrier in rabbits 1. Radiology 220:640–646
Poon C, McMahon D, Hynynen K (2016) Noninvasive and targeted delivery of therapeutics to the brain using focused ultrasound. Neuropharmacol. doi:10.1016/j.neuropharm.2016.02.014
Treat LH, McDannold N, Zhang Y et al (2012) Improved anti-tumor effect of liposomal doxorubicin after targeted blood-brain barrier disruption by MRI-guided focused ultrasound in rat glioma. Ultrasound Med Biol 38:1716–1725
Nance E, Timbie K, Miller GW et al (2014) Non-invasive delivery of stealth, brain-penetrating nanoparticles across the blood−brain barrier using MRI-guided focused ultrasound. J Control Release 189:123–132
Caskey CF, Fite B, Lai CY, (2013) Treatment of brain metastases combining ultrasound, microbubbles, and therapeutics. World Molecular Imaging Congress
Carpentier A, Canney M, Vignot A et al (2016) Clinical trial of blood-brain barrier disruption by pulsed ultrasound. Sci Transl Med 8:343re2
Konofagou E, Samiotaki G, Wang S (2015) Neuroprotection and neuroregeneration triggered through the FUS-induced opening of the blood-brain barrier in a Parkinson’s mouse model. J Therap Ultrasound. doi:10.1186/2050-5736-3-S1-O19
Samiotaki G, Acosta C, Wang S, Konofagou EE (2015) Enhanced delivery and bioactivity of the neurturin neurotrophic factor through focused ultrasound—mediated blood–brain barrier opening in vivo. J CerebBlood Flow Metab 35:611–622
Tan J-KY, Pham B, Zong Y et al (2016) Microbubbles and ultrasound increase intraventricular polyplex gene transfer to the brain. J Control Release 231:86–93
Burgess A, Dubey S, Yeung S et al (2014) Alzheimer disease in a mouse model: MR imaging–guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior. Radiology 273:736–745
Jordão JF, Thévenot E, Markham-Coultes K et al (2013) Amyloid-β plaque reduction, endogenous antibody delivery and glial activation by brain-targeted, transcranial focused ultrasound. Exp Neurol 248:16–29
Leinenga G, Götz J (2015) Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model. Sci Transl Med 7:278ra33
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Caskey, C. Ultrasound Molecular Imaging and Drug Delivery. Mol Imaging Biol 19, 336–340 (2017). https://doi.org/10.1007/s11307-017-1058-x
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DOI: https://doi.org/10.1007/s11307-017-1058-x