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In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages.

ABSTRACT: Early diagnosis, accurate staging, and image-guided resection of melanomas remain crucial clinical objectives for improving patient survival and treatment outcomes. Conventional techniques cannot meet this demand because of the low sensitivity, low specificity, poor spatial resolution, shallow penetration, and/or ionizing radiation. Here we overcome such limitations by combining high-resolution photoacoustic tomography (PAT) with extraordinarily optical absorbing gold nanocages (AuNCs). When bioconjugated with [Nle(4),D-Phe(7)]-alpha-melanocyte-stimulating hormone, the AuNCs can serve as a novel contrast agent for in vivo molecular PAT of melanomas with both exquisite sensitivity and high specificity. The bioconjugated AuNCs enhanced contrast approximately 300% more than the control, PEGylated AuNCs. The in vivo PAT quantification of the amount of AuNCs accumulated in melanomas was further validated with inductively coupled plasma mass spectrometry (ICP-MS).

SUBMITTER: Kim C

PROVIDER: S-EPMC3065066 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages.

Kim Chulhong C Cho Eun Chul EC Chen Jingyi J Song Kwang Hyun KH Au Leslie L Favazza Christopher C Zhang Qiang Q Cobley Claire M CM Gao Feng F Xia Younan Y Wang Lihong V LV

ACS nano 20100801 8

Early diagnosis, accurate staging, and image-guided resection of melanomas remain crucial clinical objectives for improving patient survival and treatment outcomes. Conventional techniques cannot meet this demand because of the low sensitivity, low specificity, poor spatial resolution, shallow penetration, and/or ionizing radiation. Here we overcome such limitations by combining high-resolution photoacoustic tomography (PAT) with extraordinarily optical absorbing gold nanocages (AuNCs). When bio ...[more]

PMID: 20731439

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Project description:Photoacoustic tomography (PAT) combines optical and acoustic imaging to generate high-resolution images of microvasculature. Inherent sensitivity to hemoglobin permits PAT to image blood vessels but precludes discriminating neovascular from maturing microvasculature. ?(v)?(3)-Gold nanobeacons (?(v)?(3)-GNBs) for neovascular molecular PAT were developed, characterized, and demonstrated in vivo using a mouse Matrigel-plug model of angiogenesis. PAT results were microscopically corroborated with fluorescent ?(v)?(3)-GNB localization and supporting immunohistology in Rag1(tm1Mom) Tg(Tie-2-lacZ)182-Sato mice. ?(v)?(3)-GNBs (154 nm) had 10-fold greater contrast than blood on an equivolume basis when imaged at 740 nm to 810 nm in blood. The lowest detectable concentration in buffer was 290 nM at 780 nm. Noninvasive PAT of angiogenesis using a 10-MHz ultrasound receiver with ?(v)?(3)-GNBs produced a 600% increase in signal in a Matrigel-plug mouse model relative to the inherent hemoglobin contrast pretreatment. In addition to increasing the contrast of neovessels detected at baseline, ?(v)?(3)-GNBs allowed visualization of numerous angiogenic sprouts and bridges that were undetectable before contrast injection. Competitive inhibition of ?(v)?(3)-GNBs with ?(v)?(3)-NBs (no gold particles) almost completely blocked contrast enhancement to pretreatment levels, similar to the signal from animals receiving saline only. Consistent with other studies, nontargeted GNBs passively accumulated in the tortuous neovascular but provided less than half of the contrast enhancement of the targeted agent. Microscopic studies revealed that the vascular constrained, rhodamine-labeled ?(v)?(3)-GNBs homed specifically to immature neovasculature (PECAM(+), Tie-2(-)) along the immediate tumor periphery, but not to nearby mature microvasculature (PECAM(+), Tie-2(+)). The combination of PAT and ?(v)?(3)-GNBs offered sensitive and specific discrimination and quantification of angiogenesis in vivo, which may be clinically applicable to a variety of highly prevalent diseases, including cancer and cardiovascular disease.

Dataset Information

In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages.

Publications

In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages.

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