Near-infrared Optical Imaging Research Articles

Letter: Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery.

Letter: Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery.

In vivo imaging of endothelial cell adhesion molecule expression after radiosurgery in an animal model of arteriovenous malformation.

Focussed radiosurgery may provide a means of inducing molecular changes on the luminal surface of diseased endothelium to allow targeted delivery of novel therapeutic compounds. We investigated the potential of ionizing radiation to induce surface expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells (EC) in vitro and in vivo, to assess their suitability as vascular targets in irradiated arteriovenous malformations (AVMs). Cultured brain microvascular EC were irradiated by linear accelerator at single doses of 0, 5, 15 or 25 Gy and expression of ICAM-1 and VCAM-1 measured by qRT-PCR, Western, ELISA and immunocytochemistry. In vivo, near-infrared (NIR) fluorescence optical imaging using Xenolight 750-conjugated ICAM-1 or VCAM-1 antibodies examined luminal biodistribution over 84 days in a rat AVM model after Gamma Knife surgery at a single 15 Gy dose. ICAM-1 and VCAM-1 were minimally expressed on untreated EC in vitro. Doses of 15 and 25 Gy stimulated expression equally; 5 Gy was not different from the unirradiated. In vivo, normal vessels did not bind or retain the fluorescent probes, however binding was significant in AVM vessels. No additive increases in probe binding were found in response to radiosurgery at a dose of 15 Gy. In summary, radiation induces adhesion molecule expression in vitro but elevated baseline levels in AVM vessels precludes further induction in vivo. These molecules may be suitable targets in irradiated vessels without hemodynamic derangement, but not AVMs. These findings demonstrate the importance of using flow-modulated, pre-clinical animal models for validating candidate proteins for vascular targeting in irradiated AVMs.

P366 Multimodal EEG/ECOG and fast optical signal measurements in interictal epileptic spikes

Objectives Although many studies in epilepsy have examined the synaptic mechanisms constituting the basis for most of the current principles of brain activity, relatively less studies have tried to characterize changes in the cellular environment that might predispose a network to pathologic synchronization. Methods In this study, near-infrared optical imaging was used with ECoG and EEG to investigate variations in the optical properties of cortical tissue directly associated with neuronal activity in 15 rats and 3 human epileptic patients. Time-frequency analysis was also used to track variations of (de) synchronization concomitantly with changes in optical signals during IES. Results Changes in Fast optical signals (FOS) occurred 320 ms before to 370 ms after the IES peak. These changes started before any changes in ECoG signal. In addition, time-frequency domain ECoG revealed an alternating decrease-increase-decrease in the ECoG spectral power (pointing to desynchronization-synchronization-desynchronization), which occurred concomitantly with an increase-decrease-increase in relative optical signal (pointing to shrinking-swelling-shrinking of the neuronal assembly) during the IES. Discussion These relationships between electrical and optical changes highlights the complexity of the interplay between the neuronal network activity and its environment around an IES. Conclusions These changes in the neuronal environment around IESs raise new questions about the mechanisms that provides the suitable conditions for the neuronal synchronization during IESs. Significance The multimodal-multiscale FOS-ECoG approach opens new avenues to better analyze the mechanisms of neuronal synchronization in the pathologic epileptic brain, which is applicable in clinic.

Near-Infrared Optical Imaging of Necrotic Cells by Photostable Lanthanide-Based Metallacrowns.

Sensitive detection of cell necrosis is crucial for the determination of cell viability. Because of its high resolution at the cellular level and sensitivity, optical imaging is highly attractive for identifying cell necrosis. However, challenges associated with this technique remain present such as the rapid photobleaching of several types of organic fluorophores and/or the interference generated by biological autofluorescence. Herein, we synthesized novel biologically compatible Zn2+/Ln3+ metallacrowns (MCs) that possess attractive near-infrared (NIR) emission and are highly photostable. In addition, these MCs have the ability to label differentially necrotic HeLa cells from living cells. This work is also the first demonstration of (i) the use of the NIR emission arising from a single lanthanide(III) cation for optical biological imaging of cells under single photon excitation, (ii) the first example of a lanthanide(III)-based NIR-emitting probe that can be targeted to a specific type of cell.

Abstract P4-01-01: Phase II in-human dose escalation study of the optical molecular imaging tracer bevacizumab-800cw for molecular fluorescence guided surgery in primary breast cancer patients

Abstract Introduction Molecular Fluorescence Guided Surgery (MFGS) might be used for intraoperative detection of positive resection margins in breast conserving surgery (BCS) for the treatment of breast cancer. Currently, the presence of tumor positive resection margins can only be assessed ex vivo by histopathological analysis of the excised tissue, which takes up to 5 working days. The current study defined the optimal dose of the near-infrared (NIR) optical imaging tracer bevacizumab-800CW to enable intraoperative detection and image-guided pathology of tumor positive resection margins in breast cancer patients. Methods Molecular Fluorescence Guided Surgery during BCS was performed in subjects treated for primary breast cancer. The NIR optical imaging tracer bevacizumab-800CW targeting vascular endothelial growth factor A was administered intravenously three days prior to surgery in four escalating dose groups (4.5mg, 10mg, 25mg and 50mg). NIR fluorescent signals were detected real-time using an intraoperative fluorescence camera system (SurgVision BV). Standardized ex vivo analyses of tumor-to-normal ratios (TNR) were performed to define the optimal tracer dose using a BlackBox imaging system (SurgVision BV) for imaging fresh bread loaf slices, a NIR fluorescence flatbed scanner (Odyssey, Li-Cor) for imaging 10µm slices of formalin-fixed paraffin-embedded (FFPE) blocks, NIR Confocal Laser Endomicroscopy (CLE, Mauna Kea Technologies) and multi-diameter single fiber reflectance and single fiber fluorescence (MDSFR/SFF) spectroscopy quantification to enable correction for the influence of tissue optical properties on fluorescence in tumor and normal breast tissue. Results Currently, 12 subjects have been included and analyzed in four dosing groups. All tumors showed specific tracer uptake at macroscopic and microscopic level during ex vivo analyses, confirmed by histopathology. Quantification of NIR fluorescent signals showed higher TNRs by increasing doses up to 25mg. No further increase in TNR was seen in the 50mg dose group. CLE showed the feasibility of visualization of the tracer accumulation in tumor tissue compared to normal tissue at a microscopic level. MDSFR/SFF spectroscopy objectively confirmed the dose dependency up to 25mg. Conclusion and future perspective Intravenous administration of bevacizumab-800CW in doses up to 50mg is safe and highly tumor specific, showing a plateau of TNR at 25mg and 50mg. Further expansion of the dosing cohorts of 10mg and 25mg with additional seven patients per group will be performed to establish the optimal dose for MFGS during BCS for an upcoming phase III multicenter randomized controlled trial. By enabling MFGS during BCS the surgical treatment of primary breast cancer patients might be optimized by a reduced need for re-excision surgery and thereby reducing the risk of co-morbidity, psychological burden, poor cosmesis and healthcare costs. Citation Format: van Dam GM, Koller M, Qiu SQ, Linssen MD, de Vries J, Jansen L, Kelder W, de Jong JS, Jorritsma-Smit A, van der Vegt B, Robinson DJ, Nagengast WB. Phase II in-human dose escalation study of the optical molecular imaging tracer bevacizumab-800cw for molecular fluorescence guided surgery in primary breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-01-01.

Shedding light on interictal epileptic spikes: An in vivo study using fast optical signal and electrocorticography.

Interictal epileptic spikes (IESs), apart from being a key marker of epileptic neuronal networks, constitute a nice model of the widespread endogenous phenomenon of neuronal hypersynchronization. Many questions concerning the mechanisms that drive neurons to hypersynchronize remain unresolved, but synaptic as well as nonsynaptic events are likely to be involved. In this study, changes in optical properties of neural tissues were observed in rats with penicillin-induced IES using fast optical signal (FOS) concomitantly with electrocorticography (ECoG). In this study, near-infrared optical imaging was used with ECoG to investigate variations in the optical properties of cortical tissue directly associated with neuronal activity in 15 rats. FOS changes correspond to variations of scattered light from neuronal tissue when neurons are activated. To independently evaluate our method, a control experiment on somatosensory was designed and applied to seven different rats. Time-frequency analysis was also used to track variations of (de)synchronization concomitantly with changes in optical signals during IES. FOS responses revealed that changes in optical signals occurred 320 msec before to 370 msec after the IES peak. These changes started before any changes in ECoG signal. In addition, time-frequency domain electrocorticography revealed an alternating decrease-increase-decrease in the ECoG spectral power (pointing to desynchronization-synchronization-desynchronization), which occurred concomitantly with an increase-decrease-increase in relative optical signal during the IES. These results suggest a relationship between (de)synchronization and optical changes. These changes in the neuronal environment around IESs raise new questions about the mechanisms that induce changes in optical properties of neural tissues before the IES, which may provide suitable conditions for neuronal synchronization during IESs. FOS-ECoG constitutes a multimodal approach and opens new avenues to study the mechanisms of neuronal synchronization in the pathologic brain, which has clinical implications, at least in epilepsy.

A high-contrast imaging survey of nearby red supergiants

AbstractMass-loss in cool supergiants remains poorly understood, but is one of the key elements in their evolution towards exploding as supernovae. Some show evidence of asymmetric mass loss, discrete mass-ejections and outbursts, with seemingly little to distinguish them from more quiescent cases. To explore the prevalence of discrete ejections and companions we have conducted a high-constrast survey using near-infrared imaging and optical polarimetric imaging of nearby southern and equatorial red supergiants, using the extreme adaptive optics instrument SPHERE, which was designed to image planets around nearby stars. We present the initial results of this survey, including the detection of large (500 nm) dust grains in the ejecta of VY CMa and a candidate dusty torus aligned with the maser ring of VX Sgr. We briefly speculate on the consequences for our understanding of mass loss in these extreme stars.

Synthesis and characterization of Na(Gd0.5Lu0.5)F4: Nd3+,a core-shell free multifunctional contrast agent

Compared to conventional core-shell structures, core-shell free nanoparticles with multiple functionalities offer several advantages such as minimal synthetic complexity and low production cost. In this paper, we present the synthesis and characterization of Nd3+ doped Na(Gd0.5Lu0.5)F4 as a core-shell free nanoparticle system with three functionalities. Nanocrystals with 20 nm diameter, high crystallinity and a narrow particle size distributions were synthesized by the solvothermal method and characterized by various analytical techniques to understand their phase and morphology. Fluorescence characteristics under near infrared (NIR) excitation at 808 nm as well as X-ray excitation were studied to explore their potential in NIR optical and X-ray imaging. At 1.0 mol% Nd concentration, we observed a quantum yield of 25% at 1064 nm emission with 13 W/cm2 excitation power density which is sufficiently enough for imaging applications. Under 130 kVp (5 mA) power of X-ray excitation, Nd3+ doped Na(Gd0.5Lu0.5)F4 shows the characteristic emission bands of Gd3+ and Nd3+ with the strongest emission peak at 1064 nm due to Nd3+. Furthermore, magnetization measurements show that the nanocrystals are paramagnetic in nature with a calculated magnetic moment per particle of ∼570 μB at 2T. These preliminary results support the suitability of the present nanophosphor as a multimodal contrast agent with three imaging features viz. optical, magnetic and X-ray.

Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery.

Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense. To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease. Fifteen patients were identified and administered a Food and Drug Administration-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) before surgical resection. An NIR camera was utilized to localize the tumor before resection and to visualize surgical margins following resection. Neuropathology and magnetic resonance imaging data were used to assess the accuracy and precision of NIR fluorescence in identifying tumor tissue. NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low-grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12 of 15 tumors were visualized with the NIR camera. The mean signal-to-background ratio was 9.5 ± 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with signal-to-background ratio (P = .03). Nonenhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71). With the use of Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity. 5-ALA, 5-aminolevulinic acidEPR, enhanced permeability and retentionFDA, Food and Drug AdministrationGBM, glioblastomaICG, indocyanine greenNIR, near-infraredNPV, negative predictive valuePPV, positive predictive valueROC, receiver operating characteristicROI, region of interestSBR, signal-to-background ratioWHO, World Health Organization.

Single dose of bisphosphonate preserves gains in bone mass following cessation of sclerostin antibody in Brtl/+ osteogenesis imperfecta model

Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in osteoporotic patients have demonstrated that sclerostin antibody, like intermittent PTH treatment, requires sequential anti-resorptive therapy to preserve the anabolic effects in adult populations. However, the persistence of anabolic gains from either drug has not been explored clinically in OI, or in any animal model. To determine whether cessation of sclerostin antibody therapy in a growing OI skeleton requires sequential anti-resorptive treatment to preserve anabolic gains in bone mass, we treated 3week old Brtl/+ and wild type mice for 5weeks with SclAb, and then withdrew treatment for an additional 6weeks. Trabecular bone loss was evident following cessation, but was preserved in a dose-dependent manner with single administration of pamidronate at the time of cessation. In vivo longitudinal near-infrared optical imaging of cathepsin K activation in the proximal tibia suggests an anti-resorptive effect of both SclAb and pamidronate which is reversed after three weeks of cessation. Cortical bone was considerably less susceptible to cessation effects, and showed no structural or functional deficits in the absence of pamidronate during this cessation period. In conclusion, while SclAb induces a considerable anabolic gain in the rapidly growing Brtl/+ murine model of OI, a single sequential dose of antiresorptive drug is required to maintain bone mass at trabecular sites for 6weeks following cessation.

Theranostic Polyaminocarboxylate-Cyanine-Transferrin Conjugate for Anticancer Therapy and Near-Infrared Optical Imaging.

Iron chelation therapy has been recognized as a promising antitumor therapeutic strategy. Herein we report a novel theranostic agent for targeted iron chelation therapy and near-infrared (NIR) optical imaging of cancers. The theranostic agent was prepared by incorporation of a polyaminocarboxylate-based cytotoxic chelating agent (N-NE3TA; 7-[2-[(carboxymethyl)amino]ethyl]-1,4,7-triazacyclononane-1,4-diacetic acid) and a NIR fluorescent cyanine dye (Cy5.5) onto a tumor-targeting transferrin (Tf). The N-NE3TA-Tf conjugate (without Cy5.5) was characterized and evaluated for antiproliferative activity in HeLa, HT29, and PC3 cancer cells, which have elevated expression levels of the transferrin receptor (TfR). The N-NE3TA-Tf conjugate displayed significant inhibitory activity against all three cancer cell lines. The NIR dye Cy5.5 was then incorporated into N-NE3TA-Tf, and the resulting cytotoxic and fluorescent transferrin conjugate N-NE3TA-Tf-Cy5.5 was shown by microscopy to enter TfR-overexpressing cancer cells. This theranostic conjugate has potential application for dual use in targeted iron chelation cancer therapy and NIR fluorescence imaging.

Multimodal near-infrared-emitting PluS Silica nanoparticles with fluorescent, photoacoustic, and photothermal capabilities.

PurposeThe aim of the present study was to develop nanoprobes with theranostic features, including – at the same time – photoacoustic, near-infrared (NIR) optical imaging, and photothermal properties, in a versatile and stable core–shell silica-polyethylene glycol (PEG) nanoparticle architecture.Materials and methodsWe synthesized core–shell silica-PEG nanoparticles by a one-pot direct micelles approach. Fluorescence emission and photoacoustic and photothermal properties were obtained at the same time by appropriate doping with triethoxysilane-derivatized cyanine 5.5 (Cy5.5) and cyanine 7 (Cy7) dyes. The performances of these nanoprobes were measured in vitro, using nanoparticle suspensions in phosphate-buffered saline and blood, dedicated phantoms, and after incubation with MDA-MB-231 cells.ResultsWe obtained core–shell silica-PEG nanoparticles endowed with very high colloidal stability in water and in biological environment, with absorption and fluorescence emission in the NIR field. The presence of Cy5.5 and Cy7 dyes made it possible to reach a more reproducible and higher doping regime, producing fluorescence emission at a single excitation wavelength in two different channels, owing to the energy transfer processes within the nanoparticle. The nanoarchitecture and the presence of both Cy5.5 and Cy7 dyes provided a favorable agreement between fluorescence emission and quenching, to achieve optical imaging and photoacoustic and photothermal properties.ConclusionWe obtained rationally designed nanoparticles with outstanding stability in biological environment. At appropriate doping regimes, the presence of Cy5.5 and Cy7 dyes allowed us to tune fluorescence emission in the NIR for optical imaging and to exploit quenching processes for photoacoustic and photothermal capabilities. These nanostructures are promising in vivo theranostic tools for the near future.

Near-Infrared Optical Imaging Noninvasively Detects Acutely Damaged Muscle

Muscle damage is currently assessed through methods such as muscle biopsy, serum biomarkers, functional testing, and imaging procedures, each with its own inherent limitations, and a pressing need for a safe, repeatable, inexpensive, and noninvasive modality to assess the state of muscle health remains. Our aim was to develop and assess near-infrared (NIR) optical imaging as a novel noninvasive method of detecting and quantifying muscle damage. An immobilization-reambulation model was used for inducing muscle damage and recovery in the lower hindlimbs in mice. Confirmation of muscle damage was obtained using invivo indocyanine green-enhanced NIR optical imaging, magnetic resonance imaging, and exvivo tissue analysis. The soleus of the immobilized-reambulated hindlimb was found to have a greater amount of muscle damage compared to that in the contralateral nonimmobilized limb, confirmed by invivo indocyanine green-enhanced NIR optical imaging (3.86-fold increase in radiant efficiency), magnetic resonance imaging (1.41-fold increase in T2), and an exvivo spectrophotometric assay of indocyanine green uptake (1.87-fold increase in normalized absorbance). Contrast-enhanced NIR optical imaging provides a sensitive, rapid, and noninvasive screening method that can be used for imaging and quantifying muscle damage and recovery invivo.

Synthesis, Characterization, In Vivo Imaging, Hemolysis, and Toxicity of Hydrophilic Ag2S Near-Infrared Quantum Dots

Ag2S quantum dots (Qds) are a new type of near-infrared Qds and hold great potential for in vivo imaging. There is great demand for versatile, practical, and environmentally-friendly processes for formation of hydrophilic Ag2S Qds. The present study prepared hydrophilic Ag2S near-infrared Qds using a simple, easy, one-step method. The Qds were characterized by TEM, XRD, FT-IR, UV–Visible and PL spectroscopy and the effect of the reaction variables of time, temperature, precipitation agent feeding rate, and S:Ag molar ratio on the size and PL spectrum of the Ag2S Qds was investigated. The Qds exhibited near-infrared photoluminescence and good photostability, which was evaluated under different conditions. Cytotoxicity tests were carried out on human A549 and Hep G2 cell lines at concentrations of 6.25–200 µg/ml. MTT assay revealed that the Qds showed no significant toxicity. The effect of plasma and corona proteins on the hemolytic activity of Ag2S Qds in four concentrations was evaluated for rat and human red blood cells. In vivo imaging showed that the Ag2S Qds penetrated the body of mice with excellent brightness. The hydrophilic Ag2S Qds can be safely applied as near-infrared optical imaging probes for nanodiagnostics or in vivo imaging.

Near-infrared fluorescence optical imaging demonstrates that C5a-C5aR1 signaling impairs normal lymphatic function

Near-infrared fluorescence optical imaging demonstrates that C5a-C5aR1 signaling impairs normal lymphatic function

Nanoprobes for Multimodal Visualization of Bone Mineral Phase in Magnetic Resonance and Near-Infrared Optical Imaging

Imaging agents with affinity for bone can enable early detection of changes to bone mineral density, which is a hallmark of many bone-associated pathologies such as Paget’s disease and osteoporosis. Here, we report the development of a polymer nanoparticle (NP)-based multimodal imaging probe that enables visualization of bone mineral phase in near-infrared (NIR) optical tomography and detection in T2-weighted magnetic resonance imaging (MRI). Ultrasmall superparamagnetic iron oxide was first encapsulated in NPs derived by blending poly(dl-lactic-co-glycolic acid)–poly(ethylene glycol) (PLGA–PEG) with N-hydroxysuccinimide functionalized-PLGA (NHS–PLGA). Postmodification of NHS surface functionality on the NPs with alendronic acid (Aln), a bone-targeting ligand, yielded stable ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) containing NPs that exhibit good serum stability and favorable cytocompatibility. These post-Aln-modified NPs exhibit 8- to 10-fold higher affinity for synthetic and biogenic hydroxyapatite in comparison to NPs where Aln was introduced before NP formation and shorten the T2 relaxation times in both agarose phantoms and fresh spongy bone, thus enabling the interrogation of bone mineral phase in T2-MRI. Finally, by introducing an NIR-dye-modified PLGA during the NP formation step, NP probes that enable the visualization of bone mineral phase in both NIR optical tomography and MRI have been realized. The system presented herein meets many of the criteria for clinical translation and therefore opens new opportunities for bone imaging and targeted therapeutics.

Near-Infrared Optical Imaging for Diagnosis of Maxillary Sinusitis.

Computed tomography (CT) is the current gold standard imaging for chronic rhinosinusitis (CRS) but is limited by cost, risk of radiation, and difficulty of being performed in the typical outpatient primary care setting. We describe the novel use of a low-cost, handheld technology to deliver an intraoral near-infrared (NIR) wavelength light to optically image the maxillary sinuses. Digital images were collected for subjects presenting with sinus disease using an intraoral NIR light source for transillumination of the maxillary sinuses, captured by a modified digital single-lens reflex camera. Light intensity contrasts were enhanced using computer analysis and subsequently compared to CT findings. NIR illumination produced unique patterns reflecting different disease states: normal sinus anatomy, mild sinus disease and/or mucosal thickening, and complete opacification of the sinus. Current results suggest that NIR imaging may facilitate the diagnosis of sinusitis in the outpatient setting with minimal cost and no radiation exposure.

Near-infrared fluorescent aza-BODIPY dye-loaded biodegradable polymeric nanoparticles for optical cancer imaging

Nanoparticles are being readily investigated as carriers for the delivery of imaging and therapeutic agents for the detection, monitoring, and treatment of cancer and other diseases. In the present work, the preparation of biodegradable polymeric nanoparticles loaded with a near-infrared fluorescent aza-boron dipyrromethene (NIR-BODIPY) derivative, and their use as contrast agents for optical imaging in cancer are described. Nanoparticles were prepared by nanoprecipitation of amphiphilic block copolymers of poly(lactic acid) and poly(ethylene glycol). The size, morphology, dye loading, spectral properties, quantum yield, cytocompatibility, and in vitro NIR imaging potential of the nanoparticles in breast and ovarian cancer cells were evaluated. Spherical nanoparticles of 30–70 nm in diameter were loaded with 0.73 w/w% BODIPY derivative. At this loading, the dye presented a fluorescence quantum yield in the same order of magnitude as in solution. Nanoparticle suspensions at concentrations up to 580 μg/mL were cytocompatible to breast (MDA-MB-231) and ovarian (SKOV-3 and Caov-3) cancer cells after a four-hour incubation period. Fluorescence microscopy images demonstrated the ability of the nanoparticles to act as imaging agents in all three cell lines in as little as 1 hour. The results shown indicate the potential of these NIR-BODIPY-loaded nanoparticles as contrast agents for near-infrared optical imaging in cancer.

A Comparison of Near-Infrared Diffuse Optical Imaging and 18F-FDG PET/CT for the Early Prediction of Breast Cancer Response to Neoadjuvant Chemotherapy.

In recent years, neoadjuvant chemotherapy (NAC) before surgery has become the standard of care for patients who present with advanced breast cancers or multiple lesions, in order to control distant metastases as well as reduce breast tumor size before surgery ([1][1]). The remaining medical oncology

Abstract P4-03-06: Near-infrared diffuse optical imaging for early prediction to neoadjuvant chemotherapy in patients with primary breast cancer

Abstract Background: Diffuse optical spectroscopic imaging (DOSI) can be exploited as a marker of tumor blood volume quantified by tissue hemoglobin (tHb) concentration. In DOSI, frequent measurement is possible for breast cancer patients because of its non-invasiveness. The tHb concentration determined by DOSI is expected to be a new biomarker for prediction of breast cancer response to neoadjuvant chemotherapy (NAC). Purpose: Our objective is to determine whether early change of tumor tHb concentration predicts pathological complete response (pCR) to NAC in patients with operable breast cancer. Methods: In a prospective study, one hundred patients with primary breast cancer were enrolled for primary objective analysis. The regimens of NAC were according to the standard of care. Patients underwent sequential scans using DOSI at baseline, after 1st course and 2nd course of chemotherapy. The mean value of tHb (tHbmean) concentration of the targeted lesion was measured and the percentage change in tHbmean (ΔtHbmean) concentration was calculated. Receiver operating curve analysis demonstrated diagnostic performance of DOSI for predicting a pCR. Results: In interim analysis, it was regarded as a good outcome that area under the curve (AUC) for ΔtHbmean after 1nd course was 0.797 (SE 0.104, 95%CI 0.633-0.911), and after 2st course was 0.867 (SE 0.06, 95%CI 0.715-0.956). Conclusion: DOSI could predict accurately a pCR to neoadjuvant chemotherapy in patients with primary breast cancer. Citation Format: Ogura H, Yoshizawa N, Ueda S, Hosokawa Y, Matsunuma R, Tochikubo J, Nasu H, Shigekawa T, Takeuchi H, Osaki A, Saeki T, Yoshimoto K, Ohmae E, Suzuki T, Ueda Y, Yamashita Y, Sakahara H. Near-infrared diffuse optical imaging for early prediction to neoadjuvant chemotherapy in patients with primary breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-03-06.