Biomedical Engineering Reference
In-Depth Information
1 cm
(a)
(b)
FIGURE 4.5
(See.color.insert.).Three-dimensional.(3D).neovascular.maps.in.Vx-2.tumors..With.MRI.and.α
ν
β
3
-targeted.nano-
particles,.areas.of.angiogenesis.surrounding.Vx-2.tumors.can.be.highlighted.(dark.blue).on.3D.mesh.models.
of. the. tumor. (digitally. resected. from. the. 3D. image. data. set).. These. two. tumors. are. the. same. age,. but. tumor.
(a).received.antiangiogenic.therapy.through.α
ν
β
3
-targeted.fumagillin-laden.theragnostic.nanoparticles.16.days.
prior. to. this. imaging. and. is. much. smaller. than. tumor. (b),. which. received. only. drug-free. particles. for. imag-
ing.. Note. the. heterogeneous. distribution. of. neovasculature. around. both. the. treated. and. nontreated. tumor..
(Reprinted.with.permission.from.Winter,.P.M.
,
et.al.,.
Faseb J
,.22,.2758-2767,.2008.)
The. beneits. of. rapid. feedback—vs.. a. wait-and-see. method. taking. weeks,. months,. even.
years—are.obvious.
In.the.examples.of.both.cancer
48
.and.atherosclerosis,
74
.clear.evidence.of.the.regression.
of.disease.was.measured.within.a.week.of.the.initial.therapy..Beyond.that,.serial.imaging.
over.multiple.weeks.perceived.the.recrudescence.of.atherosclerosis.in.fat-fed.rabbits.after.
the.one-time.therapy.effects.subsided.
82
.One.week.following.a.single.treatment.by.fumagil-
lin-laden.targeted.nanoparticles,.the.amount.of.angiogenesis.had.regressed.to.about.one-
quarter.the.value.seen.in.the.controls..However,.over.the.following.3.weeks,.the.amount.
of.atherosclerotic-related.neo-vasculature.returned.to.the.level.measured.in.the.controls..
The.response.was.similar.independent.of.the.two.dosages.tested,.i.e.,.30.and.90.µg/kg..In.
a.similar.study,.this.temporal.tool.was.used.to.evaluate.the.combination.effects.of.tradi-
tional. therapy. (i.e.,. oral. atorvastatin). in. conjunction. with. targeted. nanotherapeutics.. As.
before,.the.single.dose.of.nanotherapy.induced.a.signiicant.antiangiogenic.response.that.
was.monitored.weekly.by.molecular.imaging..By.the.fourth.week,.when.the.level.of.angio-
genesis.had.returned,.a.second.dose.of.nanotherapeutics.was.administered,.generating.the.
same.intermittent.response.as.monitored.by.diagnostic.nanoparticles..However,.in.those.
subjects.receiving.dietary.atorvastatin.in.combination.with.the.theragnostic.nanoparticles,.
the.antiangiogenic.effect.persisted.to.the.end.of.the.8-week.study..In.the.clinic,.this.type.of.
swift.and.repeatable.interrogation.of.drug.eficacy.can.lead.to.more.timely.adjustments.in.
therapy,.thereby.improving.patient.outcomes.
