Imaging prostate cancer lymph node metastases with a multimodality contrast agent

Hall, Mary; Kwon, Sunkuk; Robinson, Holly; Lachance, Pier-Anne; Azhdarinia, Ali; Ranganathan, Ranjani; Price, Roger E.; Chan, Wenyaw; Sevick‐Muraca, Eva M.

doi:10.1002/pros.21413

Cited by 52 publications

(62 citation statements)

References 66 publications

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“…However, this method does not provide functional or longitudinal imaging 17,18 . LN metastases can be imaged using a Siemens Inveon PET/CT; however, this technique does not allow visualization of lymphatic structure or function 19 .…”

Section: Discussionmentioning

confidence: 99%

Non-invasive Optical Imaging of the Lymphatic Vasculature of a Mouse

Robinson

Kwon

Hall

et al. 2013

JoVE

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The lymphatic vascular system is an important component of the circulatory system that maintains fluid homeostasis, provides immune surveillance, and mediates fat absorption in the gut. Yet despite its critical function, there is comparatively little understanding of how the lymphatic system adapts to serve these functions in health and disease 1. Recently, we have demonstrated the ability to dynamically image lymphatic architecture and lymph "pumping" action in normal human subjects as well as in persons suffering lymphatic dysfunction using trace administration of a near-infrared fluorescent (NIRF) dye and a custom, Gen III-intensified imaging system [2][3][4] . NIRF imaging showed dramatic changes in lymphatic architecture and function with human disease. It remains unclear how these changes occur and new animal models are being developed to elucidate their genetic and molecular basis. In this protocol, we present NIRF lymphatic, small animal imaging 5,6 using indocyanine green (ICG), a dye that has been used for 50 years in humans 7, and a NIRF dye-labeled cyclic albumin binding domain (cABDIRDye800) peptide that preferentially binds mouse and human albumin 8 . Approximately 5.5 times brighter than ICG, cABD-IRDye800 has a similar lymphatic clearance profile and can be injected in smaller doses than ICG to achieve sufficient NIRF signals for imaging 8 . Because both cABD-IRDye800 and ICG bind to albumin in the interstitial space 8 , they both may depict active protein transport into and within the lymphatics. Intradermal (ID) injections (5-50 μl) of ICG (645 μM) or cABD-IRDye800 (200 μM) in saline are administered to the dorsal aspect of each hind paw and/or the left and right side of the base of the tail of an isoflurane-anesthetized mouse. The resulting dye concentration in the animal is 83-1,250 μg/kg for ICG or 113-1,700 μg/kg for cABD-IRDye800. Immediately following injections, functional lymphatic imaging is conducted for up to 1 hr using a customized, small animal NIRF imaging system. Whole animal spatial resolution can depict fluorescent lymphatic vessels of 100 microns or less, and images of structures up to 3 cm in depth can be acquired 9 . Images are acquired using V++ software and analyzed using ImageJ or MATLAB software. During analysis, consecutive regions of interest (ROIs) encompassing the entire vessel diameter are drawn along a given lymph vessel. The dimensions for each ROI are kept constant for a given vessel and NIRF intensity is measured for each ROI to quantitatively assess "packets" of lymph moving through vessels.

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Section: Discussionmentioning

confidence: 99%

Non-invasive Optical Imaging of the Lymphatic Vasculature of a Mouse

Robinson

Kwon

Hall

et al. 2013

JoVE

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“…The resulting immunoconjugates were purified with a Zeba spin desalting column, collected in PBS, and stored at Ϫ80°C. The number of DOTA moieties per MAb molecule was calculated according to standardized methods (26), and potency enzyme-linked immunosorbent assay (ELISAs) were used to verify that the chemical modifications did not significantly alter biological activity. Radiolabeling with 64 Cu was performed as previously described (27).…”

Section: Materials and Strainsmentioning

confidence: 99%

Targeting Pili in Enterococcal Pathogenesis

et al. 2014

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cPassive protection, the administration of antibodies to prevent infection, has garnered significant interest in recent years as a potential prophylactic countermeasure to decrease the prevalence of hospital-acquired infections. Pili, polymerized protein structures covalently anchored to the peptidoglycan wall of many Gram-positive pathogens, are ideal targets for antibody intervention, given their importance in establishing infection and their accessibility to antibody interactions. In this work, we demonstrated that a monoclonal antibody to the major component of Enterococcus faecalis pili, EbpC, labels polymerized pilus structures, diminishes biofilm formation, and significantly prevents the establishment of a rat endocarditis infection. The effectiveness of this anti-EbpC monoclonal provides strong evidence in support of its potential as a preventative. In addition, after radiolabeling, this monoclonal identified the site of enterococcal infection, providing a rare example of molecularly specific imaging of an established bacterial infection and demonstrating the versatility of this agent for use in future diagnostic and therapeutic applications.

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“…But there has been little work to use these technique to track lymph node metastases within intact animals. Previously, we have used DsRed, a red excited fluorescent protein reporter, and iRFP [3], a far red fluorescent gene reporter as a pathologically confirmed "ground truth" for ex vivo determination of cancer-positive lymph nodes in an orthotopic xenograft model of metastatic prostate cancer [4,5]. However, autofluorescence that arises from excitation of red excited fluorescent proteins can reduce contrast preventing longitudinal imaging of the early stages of metastases through the lymphatic channels.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal far red gene-reporter imaging of cancer metastasis in preclinical models: a tool for accelerating drug discovery

Zhu¹,

Robinson²,

Zhang³

et al. 2015

Biomed. Opt. Express

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Abstract:In this short communication, we demonstrate for the first time, the use of far red fluorescent gene reporter, iRFP to longitudinally and noninvasively track the in vivo process of lymphatic metastases from an orthotopic site of mammary implantation through lymphatic vessels and to draining lymph nodes. Potentially useful to accelerate cancer drug discovery as an in vivo screening tool to monitor the pharmacological arrest of metastasis, we show that the custom as well as commercial small animal imaging devices have adequate performance to detect the gene reporter in stably expressing metastatic cancer cells. ©2015 Optical Society of America

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Imaging prostate cancer lymph node metastases with a multimodality contrast agent

Cited by 52 publications

References 66 publications

Non-invasive Optical Imaging of the Lymphatic Vasculature of a Mouse

Non-invasive Optical Imaging of the Lymphatic Vasculature of a Mouse

Targeting Pili in Enterococcal Pathogenesis

Longitudinal far red gene-reporter imaging of cancer metastasis in preclinical models: a tool for accelerating drug discovery

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