Exploratory application of indocyanine green quantification in biliary atresia observational study

BackgroundIndocyanine green (ICG) is known to facilitate real-time imaging of the bile outflow during the Kasai procedure. This study explored more possibilities for applying ICG quantification in biliary atresia (BA).MethodsWe enrolled nine BA patients in this study. All patients received intravenous ICG injections before surgery and underwent Kasai operation. With a fluorescence imaging system (Nanjing Nuoyuan, REAL-IGS FLI-108) to observe the ICG and quantify the ICG fluorescence intensity (ICG-FI) changes of the hepatic portal fibrous tissue and the liver during the operation. As a short-term prognosis assessment, we monitored the postoperative ICG metabolism time in stool and used the jaundice-free (TBIL < 2 mg/dl) at 1–3 months after the operation.ResultsThe average age of the patients at the time of surgery was 73 days. There were no adverse reactions after ICG injection. All patients were observed ICG-FI increased after the dissection of hepatic portal fibrous tissue, and the ICG-FI of the liver decreased during the operation. They all received standardized treatment after surgery. Four patients completely metabolized ICG within about two weeks (no fluorescence detected in stool), and the other five were longer than two weeks. Five patients achieved a jaundice-free outcome in the short-term postoperatively, and the other four did not.ConclusionsIt is feasible to quantify ICG-FI in real-time to evaluate the anatomical degree of hepatic portal fibrous tissue in BA. The variations of ICG-FI in the liver and postoperative ICG metabolism time may be related to prognosis.     

Fluorescence guided surgery and tracer-dose,fact or fiction?

Introduction

Fluorescence guidance is an upcoming methodology to improve surgical accuracy. Challenging herein is the identification of the minimum dose at which the tracer can be detected with a clinical-grade fluorescence camera. Using a hybrid tracer such as indocyanine green (ICG)-^99mTc-nanocolloid, it has become possible to determine the accumulation of tracer and correlate this to intraoperative fluorescence-based identification rates. In the current study, we determined the lower detection limit of tracer at which intraoperative fluorescence guidance was still feasible.

Methods

Size exclusion chromatography (SEC) provided a laboratory set-up to analyze the chemical content and to simulate the migratory behavior of ICG-nanocolloid in tissue. Tracer accumulation and intraoperative fluorescence detection findings were derived from a retrospective analysis of 20 head-and-neck melanoma patients, 40 penile and 20 prostate cancer patients scheduled for sentinel node (SN) biopsy using ICG-^99mTc-nanocolloid. In these patients, following tracer injection, single photon emission computed tomography fused with computed tomography (SPECT/CT) was used to identify the SN(s). The percentage injected dose (% ID), the amount of ICG (in nmol), and the concentration of ICG in the SNs (in μM) was assessed for SNs detected on SPECT/CT and correlated with the intraoperative fluorescence imaging findings.

Results

SEC determined that in the hybrid tracer formulation, 41 % (standard deviation: 12 %) of ICG was present in nanocolloid-bound form. In the SNs detected using fluorescence guidance a median of 0.88 % ID was present, compared to a median of 0.25 % ID in the non-fluorescent SNs (p-value?<?0.001). The % ID values could be correlated to the amount ICG in a SN (range: 0.003–10.8 nmol) and the concentration of ICG in a SN (range: 0.006–64.6 μM).

Discussion

The ability to provide intraoperative fluorescence guidance is dependent on the amount and concentration of the fluorescent dye accumulated in the lesion(s) of interest. Our findings indicate that intraoperative fluorescence detection with ICG is possible above a μM concentration.

     

Cone-Beam CT-Guided Transarterial Tagging of Endophytic Renal Tumors with Indocyanine Green for Robot-Assisted Partial Nephrectomy

PurposeTo evaluate the safety, efficacy, and clinical impact of preoperative cone-beam computed tomography (CT)–guided selective embolization of endophytic renal tumors with the fluorescent dye indocyanine green (ICG) and ethiodized oil in patients undergoing robot-assisted partial nephrectomy (RAPN) using near-infrared fluorescence imaging (NIR-FI).Materials and MethodsPatients with renal endophytic tumors eligible for RAPN and transarterial embolization with ICG and ethiodized oil were prospectively enrolled. Technical success was defined as the completion of the embolization procedure. Radiographic success, defined as ethiodized oil accumulation in the nodule, was classified as poor, moderate, good, or optimal on the basis of postembolization cone-beam CT. Surgical visibility of the tumors during RAPN with the use of NIR-FI was classified as follows: (a) not visible, (b) visible with poorly defined margins, and (c) visible with well-defined margins.ResultsForty-one patients underwent preoperative selective embolization. Technical success was 100%. Ethiodized oil accumulation on cone-beam CT was poor in 2 (4.9%), moderate in 6 (14.6%), good in 25 (61.0%), and optimal in 8 (19.5%) of 41 patients. During RAPN with NIR-FI, tumors were visible with well-defined margins in 26 (63.4%), visible with blurred margins in 14 (34.1%), and not visible in 1 (2.4%) of 41 cases. There were no adverse events following endovascular embolization.ConclusionsPreoperative transarterial superselective embolization of endophytic renal tumors with ICG and ethodized oil in patients undergoing RAPN is safe and effective, allowing accurate intraoperative visualization and resection of endophytic tumors.     

ICG纳米探针在早期结肠癌诊断中的应用及其价值

 

目的 评估ICG纳米探针在结肠癌荧光分子成像中的靶向性、荧光效应及其早期诊断价值。方法 建立裸鼠结肠癌皮下移植瘤模型,应用人血清白蛋白(HSA)包裹的ICG纳米探针,并以Folate RsenseTM680、吲哚菁绿作为对照组,经裸鼠结肠癌皮下移植瘤模型尾静脉注射探针后,进行活体荧光分子成像,观察HAS-ICG纳米探针的成像效果,量化分析肿瘤部位的荧光信号强度。结果 活体荧光分子成像结果显示:探针HAS-ICG、Folate RsenseTM680均在实验瘤鼠皮下肿瘤部位出现浓聚,浓聚高峰分别在注射后1 h、24 h。与对照组相比,HAS-ICG纳米探针比商业探针有较好的靶向标记性和信噪比。结论 HSA-ICG纳米探针具有很好的标记HCT116结肠肿瘤细胞的能力,可通过荧光分子成像技术诊断早期裸鼠结肠癌变。

     

Heptamethine cyanine based 64Cu-PET probe PC-1001 for cancer imaging: Synthesis and in vivo evaluation

PurposeDevelopment of a heptamethine cyanine based tumor-targeting PET imaging probe for noninvasive detection and diagnosis of breast cancer.MethodsTumor-specific heptamethine–cyanine DOTA conjugate complexed with Cu-64 (PC-1001) was synthesized for breast cancer imaging. In vitro cellular uptake studies were performed in the breast cancer MCF-7 and noncancerous breast epithelial MCF-10A cell lines to establish tumor specificity. In vivo time-dependent fluorescence and PET imaging of breast tumor xenografts in mice were performed. Blood clearance, biodistribution, and tumor-specific uptake and plasma binding of PC-1001 were quantified. Tumor histology (H&E staining) and fluorescence imaging were examined.ResultsPC-1001 displayed similar fluorescence properties (ε = 82,880 cm^? 1 M^? 1, E_x/E_m = 750/820 nm) to the parental dye. Time-dependent cellular accumulation indicated significantly higher probe uptake (> 2-fold, 30 min) in MCF-7 than MCF-10A cells and the uptake was observed to be mediated by organic anion transport peptides (OATPs) system. In vivo studies revealed that PC-1001 has desirable accumulation profile in tumor tissues, with tumor versus muscle uptake of about 4.3 fold at 24 h and 5.8 fold at 48 h post probe injections. Blood half-life of PC-1001 was observed to be 4.3 ± 0.2 h. Microscopic fluorescence imaging of harvested tumor indicated that the uptake of PC-1001 was restricted to viable rather than necrotic tumor cells.ConclusionsA highly efficient tumor-targeting PET/fluorescence imaging probe PC-1001 is synthesized and validated in vitro in MCF-7 breast cancer cells and in vivo in mice breast cancer xenograft model.     

Indocyanine green fluorescence imaging localization: A helpful addition to laparoscopic dissection and division of rectourethral fistulae

BackgroundRectourethral fistulae (RUF) are the most prevalent type of anorectal malformations in boys, with various surgical treatment methods investigated in recent years. Currently, research is focused on preventing urethral damage or urethral diverticulum formation caused by imprecise dissection during the laparoscopically assisted anorectal pull-through (LAARP) technique. This study aimed to determine the efficacy of indocyanine green (ICG) fluorescence imaging to improve the localization and separation of the RUF during laparoscopic surgery.MethodsICG was intrarectally injected through a pre-inserted gastric tube at the distal enterostomy port to locate the fistula. This retrospective analysis included children with RUF who were treated surgically with ICG fluorescence imaging localization-assisted LAARP between January and June 2022. We investigated the patient demographics, perioperative conditions, and subsequent follow-up results.ResultsFour patients underwent ICG-assisted LAARP. Their median age was 80 days (range, 63–120) and the median duration of each procedure was 145 min (range, 120–165). Postoperatively, the duration of catheter retention and hospital stay was eight days. The children's prognosis was based on the follow-up outcomes of gastrointestinal, urinary tract function, and imaging examination. None of the included patients was diagnosed with urinary diverticulum, urinary tract injury, anal stricture, or rectal prolapse.ConclusionsInjection of ICG at the end of the rectum during LAARP surgery is a feasible adjunct for locating the RUF, providing a greater degree of accuracy for laparoscopic separation and resection of fistulae, thereby decreasing the risk of urological complications.     

The comparison of penetration depth of two different photosensitizers in root canals with and without smear layer: An in vitro study

BackgroundThe main objective of this study is to evaluate the penetration depth of suggested photosensitizers in the lateral wall of the human root canal.Materials & methodsForty extracted single-rooted human teeth with straight canals that extracted for periodontal reasons were collected and stored in the sterile saline until employment in the experiment. Teeth were decoronated to a standard 12 mm root segment using diamond disc. After instrumentation of specimens, the external root surface was sealed with two layers of nail polish to avoid environmental contamination. The apical foramen was subsequently closed with composite material. Teeth were divided randomly in two major groups consist of indocyanine green solution (ICG) and tolonium chloride solution (TCH) with and without EDTA in their subgroups. Specimens in all groups grooved longitudinally with a diamond disc and split in two halves with a stainless steel chisel. The measurements were done by the stereo microscope under 20× magnification in three zones of each specimen and the penetration depth of dye was measured.ResultsThe results of this study showed that the mean of lateral penetration depth of ICG (224.04 μm) was significantly (P < 0.05) higher than TCH (70.15 μm). Regarding to the influence of EDTA, in ICG group without consideration to the different regions, the usage of EDTA improved the mean of lateral penetration depth of ICG, but this improvement was not statistically significant (P > 0.05).ConclusionFurther to the findings of this study, it could be assumed that ICG could penetrate in deeper regions of the root canal wall.     

Polylactide nanoparticles encapsulating indocyanine green for photothermal therapy of prostate cancer cells

BackgroundThe aim of this study is to investigate the in vitro phototherapeutic potential of indocyanine green (ICG) loaded polylactide (PLA) nanoparticles on prostate cancer cells. Many attempts at designing drug delivery systems against cancer were made that incorporates ICG as a photothermal, photodynamic or imaging agent. However, most of these systems contain at least one more drug, making it hard to assess the effects of ICG alone.MethodsNanoparticles (ICGNP) were prepared via nanoprecipitation. The effects of phase volume ratio and ICG concentration on size, loading capacity and encapsulation efficiency were explored. Photothermal and photodynamic properties of ICGNP were examined. PC-3 cells were used for cell viability tests. Irradiation was achieved via custom built 809-nm computer controlled diode laser at 1 W/cm² (up to 600 J/cm²). Data were analyzed by ANOVA followed by Tukey's test (p ≤ 0.05).ResultsICGNP exhibited mean size of 300 nm with low polydispersity, and zeta potential of -14 mV. Upon laser irradiation, ICGNP were capable of causing temperature increase and producing singlet oxygen. On PC-3 cells, ICGNP were proved to be as effective as free ICG in inducing cell death. The measured temperature increase in culture medium and experiments with singlet oxygen quenchers suggest that the decrease in cell viability was mainly the result of photothermal action.ConclusionsICGNP was effective as a photothermal agent on PC-3 cells but further improvements are required to increase ICG loading capacity for it to be useful on a wide range of cell types.     

High tumor uptake of 64Cu: Implications for molecular imaging of tumor characteristics with copper-based PET tracers

IntroductionThe use of copper-based positron emission tomography (PET) tracers in cancer studies is increasing. However, as copper has previously been found in high concentrations in human tumor tissue in vivo, instability of PET tracers could result in tumor accumulation of non-tracer-bound radioactive copper that may influence PET measurements. Here we determine the degree of ⁶⁴Cu uptake in five commonly used human cancer xenograft models in mice. Additionally, we compare copper accumulation in tumor tissue to gene expression of human copper transporter 1 (CTR1).MethodsSmall animal PET scans were performed on five different human cancer xenograft mice models 1 h and 22 h post injection (p.i.) of ⁶⁴CuCl₂. Regions of interest (ROIs) were drawn on tumor tissue and sections of various organs on all images. Quantitative real-time PCR (qPCR) gene expression measurements of CTR1 were performed on tumor samples obtained after the 22 h scan.ResultsA relatively high tumor uptake of ⁶⁴Cu was seen in four out of five tumor types and an increase in ⁶⁴Cu accumulation was seen in three out of five tumor types between 1 h and 22 h p.i. No relationship was found between tumor uptake of ⁶⁴Cu and gene expression of CTR1.ConclusionsThe relatively high, time- and tumor type dependent ⁶⁴Cu uptake demonstrated here in five different human cancer xenograft models in mice, emphasizes the importance of validating tracer uptake and indicates that high in vivo stability of copper-based PET tracers is of particular importance because non-tracer-bound copper can accumulate in tumor tissue to a level that could potentially lead to misinterpretation of PET data.     

The in vitro effect of antimicrobial photodynamic therapy with toluidine blue and indocyanine green on microleakage of class V cavities

IntroductionConsidering the importance of disinfecting dentin and enamel after cavity preparation and the possible effect of disinfection methods on induction of various reactions in the tooth structure the aim of the present study was to evaluate microleakage of composite resin restoration after disinfecting the prepared dentin and enamel surface with antimicrobial photodynamic therapy (aPDT) with toluidine blue (TBO) and indocyanine green (ICG).Materials and methodsStandard class V cavities were prepared on buccal surface of 71 human premolar teeth. The samples were randomly divided into 3 groups based on disinfection method: Group 1: conventional disinfection method with Phosphoric acid 37% as the control; Group 2: aPDT with TBO and diode laser with wavelength of 635 nm; Group 3: aPDT with ICG and diode laser with wavelength of 808 nm. All the cavities were restored with composite resin (3M™ Filtek™ Z250). After thermocycling and immersing in 0.5% basic fuchsin, the samples were prepared for microleakage evaluation under a stereomicroscope. Data was analyzed with Kruskal-Wallis and Wilcoxon signed-rank tests at P < 0.05.ResultsThere were no significant differences in the microleakage of occlusal and gingival margins between the TBO and control groups (P > 0.05). Also, the microleackage of occlusal margins between groups was not significantly different (P > 0.05) but microleackage of gingival margins of ICG group was lower than two other groups in a meaningful way (P < 0.05).ConclusionPhotodynamic therapy with ICG as disinfecting agent in cavity preparations before composite resin restorations decreases the microleackage of gingival margins.     

The effect of indocyanine green loaded on a novel nano-graphene oxide for high performance of photodynamic therapy against Enterococcus faecalis

BackgroundRecently developed photodynamic therapy (PDT) has gained attention for achieving effective root canal disinfection. Using an optimized nontoxic photosensitizer (PS), such as indocyanine green (ICG), is an imperative part of this technique. Therefore, the objective of the current study was to improve ICG photodynamic properties through incorporation of ICG into nano-graphene oxide (NGO) in order to produce NGO-ICG as a new PS and also to assess the antimicrobial effects of NGO-ICG against Enterococcus faecalis after photodynamic therapy.Materials and methodsNGO-ICG was synthesized based on oxidation of graphite flakes and direct loading of ICG onto NGO. NGO-ICG formation was confirmed using the Fourier Transform Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), and UV–vis spectrometry. The antimicrobial and anti-biofilm potential of NGO-ICG-PDT against E. faecalis was assessed via colony forming unit and crystal violet assays, respectively.ResultsFT-IR, SEM and UV–vis spectrometry confirmed successful synthesis of NGO-ICG containing 200 μg/mL of ICG. NGO-ICG-PDT at an energy density of 31.2 J/cm² showed a significant reduction (2.81 log) in the count of E. faecalis (P < 0.05). NGO-ICG-PDT significantly reduced the biofilm formation ability of E. faecalis up to 99.4% (P < 0.05). The overall antimicrobial and anti-biofilm potential of NGO-ICG-PDT was higher than PDT based on ICG (1000 μg/mL) (47% and 21%, respectively).ConclusionBecause NGO-ICG-PDT showed a significant reduction in the number and biofilm formation ability of E. faecalis at low ICG concentrations (200 μg/mL), it could be a new approach to adjuvant treatment of endodontic infections.     

Preliminary low-dose photodynamic exposure to skin cancer with chlorin e6 photosensitizer

BackgroundThe study aimed to investigate the chlorin e6 photosensitizer distribution in the tumor and tumor border (5 mm) during low-dose photodynamic treatment and to increase the effectiveness of the therapy for skin neoplasms.MethodsSensitized boundaries of neoplasms were evaluated by video fluorescence imaging. The study of changes in the chlorin e6 distribution before/after photodynamic therapy and in the process of low-dose photodynamic exposure was carried out by the method of spectral fluorescence diagnostics.ResultsAll 19 patients with basal-cell skin cancer had a contrast of chlorin e6 accumulation compared to normal tissues. 3 hours after intravenous administration of the photosensitizer at a dose of 1 mg/kg, the chlorin e6 concentration was: in normal tissues - 0.18 mg/kg, in the tumor - 1.26 mg/kg, in the tumor border - 0.63 mg/kg. In most cases, the fluorescence indices of chlorin e6 in tumor tissues after low-dose photodynamic therapy increased and exceeded the values before light exposure.ConclusionLow-dose photodynamic therapy seems to be an optimal method for treating select skin neoplasms, which does not cause severe pain in patients during the light exposure and allows for local increase of the photosensitizer concentration in tumor tissues. This method of photodynamic therapy can improve the effectiveness of thе treatment.     

Safety and effectiveness of fluorescence laparoscopy in precise hepatectomy: A meta-analysis

BackgroundTo perform a systematic review of the safety and effectiveness of fluorescence laparoscopy-guided precise hepatectomy.MethodsWe searched the PubMed, Embase, Web of Science, and Cochrane Library databases from inception to December 1, 2022, using the search terms “indocyanine green,” “ICG,” “infracyanine green,” “laparoscopy,” “liver resection,” and “hepatectomy.” After performing a methodological quality assessment of the included studies, the overall results were subjected to meta-analysis using Review Manager 5.3.ResultsAfter screening, the meta-analysis included a total of 13 articles. The studies included 1,115 patients who were grouped into the fluorescence laparoscopy (490 patients) and conventional laparoscopy (625 patients) groups. All articles included in the meta-analysis were of high quality. The results of the meta-analysis revealed that compared to the conventional laparoscopy group, the fluorescence laparoscopy group had a higher R0 resection rate (odds ratio=4.03, 95% confidence interval [1.50, 10.83], P = 0.006), lower blood transfusion rate (odds ratio=0.46, 95% confidence interval [0.21, 0.97], P = 0.04) and lower blood loss (mean difference=-36.58; 95% confidence interval [-59.75, -13.41], P = 0.002). However, the length of hospital stay, operative time, and incidence of postoperative complications did not differ significantly between both groups (P>0.05).ConclusionCompared to conventional laparoscopy, fluorescence laparoscopy provides better application effects in hepatectomy. The surgical procedure has demonstrated good safety and feasibility, which make it worthy of popularization.     

Combination of hand-held probe and microscopy for fluorescence guided surgery in the brain tumor marginal zone

BackgroundVisualization of the tumor is crucial for differentiating malignant tissue from healthy brain during surgery, especially in the tumor marginal zone. The aim of the study was to introduce a fluorescence spectroscopy-based hand-held probe (HHF-probe) for tumor identification in combination with the fluorescence guided resection surgical microscope (FGR-microscope), and evaluate them in terms of diagnostic performance and practical aspects of fluorescence detection.Material and MethodsEighteen operations were performed on 16 patients with suspected high-grade glioma. The HHF-probe and the FGR-microscope were used for detection of protoporphyrin (PpIX) fluorescence induced by 5-aminolevulinic acid (5-ALA) and evaluated against histopathological analysis and visual grading done through the FGR-microscope by the surgeon. A ratio of PpIX fluorescence intensity to the autofluorescence intensity (fluorescence ratio) was used to quantify the spectra detected by the probe.ResultsFluorescence ratio medians (range 0 – 40) measured by the probe were related to the intensity of the fluorescence in the FGR-microscope, categorized as “none” (0.3, n = 131), “weak” (1.6, n = 34) and “strong” (5.4, n = 28). Of 131 “none” points in the FGR-microscope, 88 (67%) exhibited fluorescence with the HHF-probe. For the tumor marginal zone, the area under the receiver operator characteristics (ROC) curve was 0.49 for the FGR-microscope and 0.65 for the HHF-probe.ConclusionsThe probe was integrated in the established routine of tumor resection using the FGR-microscope. The HHF-probe was superior to the FGR-microscope in sensitivity; it detected tumor remnants after debulking under the FGR-microscope. The combination of the HHF-probe and the FGR-microscope was beneficial especially in the tumor marginal zone.     

Effect of various types of photodynamic therapy on inflammatory and non-inflammatory lesions in patients with acne: A network meta-analysis of randomized controlled trials

BackgroundRecent studies have demonstrated that photodynamic therapy (PDT) is safe and effective in treating acne vulgaris. The present study aimed to evaluate various PDTs on inflammatory and non-inflammatory lesions in patients with acne by a network meta-analysis (NMA) of randomized controlled trials (RCTs).MethodsThe researchers of this paper searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to March 2022 to identify suitable RCTs. The included studies were evaluated for methodological quality using the Cochrane bias risk assessment tool. Twenty-one RCTs were included, with a total sample size of 898 participants.ResultsNetwork meta-analysis (NMA) revealed that indocyanine green (ICG) + near-infrared (NIR) diode laser, ICG+830 nm light-emitting diode (LED), indole-3-acetic acid (IAA) + 520 nm LED, and 5-aminolevulinic acid (ALA) + sunlight demonstrated obvious curative effects in patients with acne vulgaris. Importantly, ICG+NIR diode laser provided the greatest improvement in both inflammatory and non-inflammatory acne lesions (surface under the cumulative ranking curve [SUCRA]: 84.4% and 93.5%, respectively).ConclusionsBased on the NWM and SUCRA ranking, ICG + NIR diode laser can be considered more effective in treating acne than the other PDTs of the RCTs. However, this conclusion should be interpreted with caution due to the limitations of the present study.     

Novel use of ViewRay MRI guidance for high-dose-rate brachytherapy in the treatment of cervical cancer

PurposeTo characterize image quality and feasibility of using ViewRay MRI (VR)–guided brachytherapy planning for cervical cancer.Methods and MaterialsCervical cancer patients receiving intracavitary brachytherapy with tandem and ovoids, planned using 0.35T VR MRI at our institution, were included in this series. The high-risk clinical target volume (HR-CTV), visible gross tumor volume, bladder, sigmoid, bowel, and rectum contours for each fraction of brachytherapy were evaluated for dosimetric parameters. Typically, five brachytherapy treatments were planned using the T2 sequence on diagnostic MRI for the first and third fractions, and a noncontrast true fast imaging with steady-state precession sequence on VR or CT scan for the remaining fractions. Most patients received 5.5 Gy × 5 fractions using high-dose-rate Ir-192 following 45 Gy of whole-pelvis radiotherapy. The plan was initiated at 5.5 Gy to point A and subsequently optimized and prescribed to the HR-CTV. The goal equivalent dose in 2 Gy fractions for the combined external beam and brachytherapy dose was 85 Gy. Soft-tissue visualization using contrast-to-noise ratios to distinguish normal tissues from tumor at their interface was compared between diagnostic MRI, CT, and VR.ResultsOne hundred and forty-two fractions of intracavitary brachytherapy were performed from April 2015 to January 2017 on 29 cervical cancer patients, ranging from stages IB1 to IVA. The median HR-CTV was 27.78 cc, with median D₉₀ HR-CTV of 6.1 Gy. The median time from instrument placement to start of treatment using VR was 65 min (scan time 2 min), compared to 105 min using diagnostic MRI (scan time 11 min) (t-test, p < 0.01). The contrast-to-noise ratio of tumor to cervix in both diagnostic MRI and VR had significantly higher values compared to CT (ANOVA and t-tests, p < 0.01).ConclusionsWe report the first clinical use of VR-guided brachytherapy. Time to treatment using this approach was shorter compared to diagnostic MRI. VR also provided significant advantage in visualizing the tumor and cervix compared to CT. This presents a feasible and reliable manner to image and plan gynecologic brachytherapy.     

肝胆肿瘤患者68Ga-FAPI-04 PET显像的内照射剂量及分布研究

目的 评估⁶⁸Ga-FAPI-04 PET/CT检查在肝胆肿瘤患者中的内照射剂量及生物分布。方法 本研究纳入因肝脏占位于北京协和医院接受PET/CT检查的6例患者,经静脉注射⁶⁸Ga-FAPI-04（170.57 ±14.43） MBq后分别于第3、10、15、20、30和60 min进行全身显像。观察显像剂的生物分布;手动勾画感兴趣区;所有靶器官的内照射剂量应用OLINDA/EXM软件计算。结果 ⁶⁸Ga-FAPI-04在肝脏内放射性本底消退较快,在肿瘤组织内放射性摄取较为稳定,病灶平均SUV_max在注射后20 min达到最大（13.87 ±2.55）;病灶平均靶本比逐渐升高,在注射后30 min达到最大（10.09 ±8.17）。1次⁶⁸Ga-FAPI-04 PET/CT扫描的全身有效剂量为（0.020 ±0.002） mSv/MBq,吸收剂量最高的器官是膀胱壁,为（0.146 ±0.035） mSv/MBq。结论 ⁶⁸Ga-FAPI-04与¹⁸F-FDG全身有效剂量相近;肿瘤摄取快速,肝脏背景低,且不受血糖水平影响,有望成为潜在的肝胆肿瘤PET/CT显像药物。     

Association of 5-aminolevulinic acid with intraoperative hypotension in malignant glioma surgery

BackgroundUse of 5-aminolevulinic acid for photodynamic malignant tumor diagnosis reportedly causes intraoperative hypotension (systolic blood pressure < 70 mmHg) during urologic surgery. However, its association with intraoperative hypotension in malignant glioma surgery and underlying mechanisms has not yet been elucidated.. This study aimed to investigate whether 5-aminolevulinic acid administration is associated with intraoperative hypotension in malignant glioma surgery and explore the mechanisms of 5-aminolevulinic acid-induced hypotension in vitro.MethodsIn this retrospective multicenter cohort study, we investigated intracellular nitric oxide as a candidate mediator of hypotension in response to 5-aminolevulinic acid in vitro in human umbilical vein endothelial cell cultures.ResultsOf 142 patients, 94 underwent 5-aminolevulinic acid-guided surgery. Systolic blood pressure was significantly lower throughout surgery with 5-aminolevulinic acid administration. 5-Aminolevulinic acid administration was an independent risk factor for intraoperative hypotension according to multivariable logistic regression analysis (89% vs. 56%; odds ratio = 6.72, 95% confidence interval [2.05–22.1], P = 002). In subgroup analysis of the 5-aminolevulinic acid group, increasing age and use of renin-angiotensin system inhibitors had a synergistic effect with 5-aminolevulinic acid on decreased blood pressure. In the vascular endothelial cell culture study, 5-aminolevulinic acid induced a significant increase in intracellular nitric oxide generation.Conclusions5-Aminolevulinic acid administration was associated with intraoperative hypotension in malignant glioma surgery, with increasing age and use of renin-angiotensin system inhibitors boosting the blood pressure-lowering effect of 5-aminolevulinic acid. According to in vitro results, the low blood pressure induced by 5-aminolevulinic acid may be mediated by a nitric oxide increase in vascular endothelial cells.     

Nanocolloidal albumin-IRDye 800CW: a near-infrared fluorescent tracer with optimal retention in the sentinel lymph node

Purpose

At present, the only approved fluorescent tracer for clinical near-infrared fluorescence-guided sentinel node (SN) detection is indocyanine green (ICG), but the use of this tracer is limited due to its poor retention in the SN resulting in the detection of higher tier nodes. We describe the development and characterization of a next-generation fluorescent tracer, nanocolloidal albumin-IRDye 800CW that has optimal properties for clinical SN detection

Methods

The fluorescent dye IRDye 800CW was covalently coupled to colloidal human serum albumin (HSA) particles present in the labelling kit Nanocoll in a manner compliant with current Good Manufacturing Practice. Characterization of nanocolloidal albumin-IRDye 800CW included determination of conjugation efficiency, purity, stability and particle size. Quantum yield was determined in serum and compared to that of ICG. For in vivo evaluation a lymphogenic metastatic tumour model in rabbits was used. Fluorescence imaging was performed directly after peritumoral injection of nanocolloidal albumin-IRDye 800CW or the reference ICG/HSA (i.e. ICG mixed with HSA), and was repeated after 24?h, after which fluorescent lymph nodes were excised.

Results

Conjugation of IRDye 800CW to nanocolloidal albumin was always about 50% efficient and resulted in a stable and pure product without affecting the particle size of the nanocolloidal albumin. The quantum yield of nanocolloidal albumin-IRDye 800CW was similar to that of ICG. In vivo evaluation revealed noninvasive detection of the SN within 5?min of injection of either nanocolloidal albumin-IRDye 800CW or ICG/HSA. No decrease in the fluorescence signal from SN was observed 24?h after injection of the nanocolloidal albumin-IRDye 800CW, while a strong decrease or complete disappearance of the fluorescence signal was seen 24?h after injection of ICG/HSA. Fluorescence-guided SN biopsy was very easy.

Conclusion

Nanocolloidal albumin-IRDye 800CW is a promising fluorescent tracer with optimal kinetic features for SN detection.