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 bio-conjugated with [Nle 4 ,D-Phe 7 ]-α-melanocytestimulating 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 bio-conjugated AuNCs enhanced contrast ~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). KeywordsPhotoacoustic tomography; gold nanocages; melanoma; bio-conjugation; molecular imagingThe 10-year survival rate of early-stage cutaneous melanoma patients is very high (~99%), but the rate drops to 40% after nodal metastases. 1,2 Thick melanomas (>4 mm) are typically associated with a high risk of nodal and distant metastases. Highly sensitive molecular imaging techniques including positron emission tomography (PET) and optical imaging have been developed for detecting early-stage melanomas. [3][4][5] However, PET requires on the use of radio-labeling materials, which can cause potential hazards to patients. Moreover, it suffers from low spatial resolution and high cost due to the need of additional anatomical information from magnetic resonance imaging (MRI) and/or X-ray computed tomography (CT). Since optical imaging uses nonionizing radiation and is cost-effective, it has received much attention in molecular imaging. 6 However, conventional optical imaging tools are often limited by either shallow penetration depth (<1 mm) 7 Besides early detection, accurate delineation of the margins of a melanoma can significantly improve surgical removal of the primary tumor. High-frequency ultrasound has been applied preoperatively for this purpose, 9 but it cannot effectively resolve the margins of a melanoma and does not infiltrate cells. Additionally, accurate staging (describing cancer metastasis, typically with numbers I to IV) of patients after nodal metastases is important for treatment planning. 10 Again, the current technique based on sentinel lymph node biopsy is ionizing and intraoperative, and thus poses postoperative complications. These limitations of the current techniques suggest a strong need for a single, highly sensitive, safe, economical, noninvasive, and high-resolution imaging technique with nonradioactive contrast agents in early diagnosis of malignant melanomas, image-guided resection of melanoma boundaries, and accurate staging of melanoma patients.PAT is a hybrid biomedical imaging modality that offers both strong optical absorption contrast...

Performance benchmarks of an array-based hand-held photoacoustic probe adapted from a clinical ultrasound system for non-invasive sentinel lymph node imaging

“…haemoglobin and melanin) or extrinsic (e.g. organic dyes and nanoparticles) contrast, high-resolution PA imaging can provide highly sensitive morphological, functional and molecular information about biological tissues [4][5][6]. Further, conventional ultrasonic scanners can serve as PA wave receivers, thus combining the high contrast of optical imaging and the high resolution of ultrasound (US) imaging [7][8][9][10].…”

Bioactive Food Components for Melanoma: An Overview

“…The nanoparticle was rapidly internalized into the lysosome of melanoma cells and was retained in the subcellular compartment for over 24 h. In an in vivo melanoma model, treatment with the nanotube-doxorubicin conjugate abrogated tumor growth without the systemic side-effects associated with free doxorubicin. High-resolution photoacoustic tomography (PAT) with extraordinarily optical absorbing gold nanocages (AuNCs) was utilized in a study [135]. When bioconjugated with [Nle(4),D-Phe(7)]-alphamelanocyte-stimulating hormone, the AuNCs served as a novel contrast agent for in vivo molecular PAT of melanomas with both exquisite sensitivity and high specificity.…”

Plasmonic Nanoparticles with Quantitatively Controlled Bioconjugation for Photoacoustic Imaging of Live Cancer Cells

“…PAI has the advantages of high optical contrast and good ultrasound penetration, and can provide multidimensional tumor data, including structural, functional, metabolic, and molecular information 7. To date, most work has been focused on solid tumor detection at the macroscopic level 7, 8, 9, 10, 11, 12, 13, 14, 15, 16. However, solid tumor usually evolves from a single cell 17.…”

“…AuNPs have already been used in PAI to image and diagnose a variety of cancers,7, 9, 10, 11, 12, 13, 14, 15, 16 such as melanoma,9 squamous cell carcinoma,10 prostate cancer,11 colon carcinoma,12 breast cancer,13 and circulating tumor cells 14, 15, 16. Several parameters, such as size, shape, and surface chemistry, are critical for their photoacoustic applications 34.…”