Biomedical Engineering Reference
In-Depth Information
speciicity. of. nanoparticle. binding. was. further. veriied. through. competitive. blockade.
experiments.
Another.disease.in.which.angiogenesis.plays.a.critical.role.is.cancer..When.the.metabolic.
demands.of.a.growing.tumor.exceed.the.supply.of.nutrients.that.can.be.delivered.via.dif-
fusion,. new. vessels. are. recruited. to. do. the. job.. Again. targeting. α
ν
β
3
,. PFC. nanoparticles.
have. been. used. to. image. this. neovasculature. in. models. of. cancer,. e.g.,. the. Vx-2. model,.
wherein. small. tumors. are. implanted. into. the. popliteal. fossa. of. rabbits. and. allowed. to.
grow.for.about.2.weeks..In.one.study
40
.using.a.clinical.1.5.T.MRI.scanner,.the.intravenously.
injected.nanoparticles.were.imaged.accumulated.at.sites.of.angiogenesis.surrounding.the.
tumor,.indicating.asymmetrical.distributions.of.neovasculature.typically.at.tumor-muscle.
interfaces. and. nearby. vasculature.. The. α
ν
β
3
-targeted. paramagnetic. nanoparticles. pro-
vided. a. signal. intensity. 126%. greater. than. that. at. baseline,. representing. a. change. twice.
that.due.to.control,.nontargeted.nanoparticles.(which.also.accumulated.nominally.due.to.
passive.extravascular.leakage)..As.with.the.atherosclerosis.experiments,.in.vivo.competi-
tive.blockade.experiments.conirmed.receptor.speciicity.of.the.targeted.agent..In.the.same.
cancer.model,.indium.(
111
In).radiolabeled.nanoparticles.were.used.to.image.the.neovascu-
lature.with.much.greater.detection.sensitivity.using.single-pinhole,.planar.nuclear.imag-
ing.techniques.
41
.Combining.the.
111
In.and.Gd-DTPA.labels.on.the.α
ν
β
3
-targeted.particles.
provided.a.unique.dual-modality.SPECT/MRI.contrast.agent.that.could.image.Vx-2.tumor.
neovascularity. with. the. increased. sensitivity. of. nuclear. images. and. the. high-resolution.
anatomical.images.of.MRI.
33
.Other.models.of.cancer.in.which.these.diagnostic.particles.
have.been.employed.successfully.are.a.human.melanoma
42
.and.breast.carcinoma
43
.in.mice..
These.models,.with.regard.to.aggressiveness.and.angiogenesis,.are.a.bit.different.from.the.
Vx-2.model,.and.those.differences.can.be.characterized.with.these.targeted.nanoparticle.
imaging.agents.
4.4 CharacterizingDisease
In.the.science.of.medical.diagnosis,.a.tool.providing.sensitive.and.speciic.detection.of.the.
presence. (or. absence). of. a. disease. is. invaluable.. Nanotechnology. offers. the. potential. to.
extend.this.one.step.further.by.characterizing.the.disease.by.the.presence.or.extent.of.cer-
tain.biological.markers..This.can.be.important.not.only.in.understanding.the.disease.type.
and. stage. in. an. individual,. but. also. in. determining. a. priori. which. therapy. will. (or. will.
not).be.effective..For.example,.in.some,.but.not.all,.breast.cancers.the.human.epidermal.
growth.factor.receptor.2.(HER2).gene.is.ampliied.
44
.In.the.25-30%.overexpressing.HER2,.
the.patients.have.a.much.poorer.prognosis.than.those.not.expressing.it,.but.fortunately,.
they.also.preferentially.respond.to.treatment.with.trastuzumab,.a.recombinant.monoclo-
nal.antibody-targeted.therapy.
45,46
.Already.mentioned.above,.for.atherosclerosis,.the.extent.
of.angiogenesis.in.the.
vasa vasorum
.is.indicative.of.the.severity.of.the.disease,
37,47
.and.the.
presence.or.absence.of.exposed.ibrin.in.a.plaque.is.useful.in.predicting.its.predilection.
to.rupture.
35,36
The.presence.and.extent.of.angiogenesis.is.an.important.marker.for.characterizing.can-
cer.. Employing. MRI. molecular. imaging. with. integrin-targeted. nanoparticles. as. before,.
Lanza.et.al..described.(quantitatively.and.visually).the.amount.of.angiogenesis.associated.
with.MDA-MB-435.breast.carcinoma
43
.and.the.more.aggressive.Vx-2.carcinoma.
48
.Not.only.
could.the.difference.in.extent.of.angiogenesis.be.distinguished.between.these.two.tumor.
