Fluorescence molecular endoscopy (FME) is an emerging technology that has the potential to increase the failure rate of colorectal polyp detection by 22%. We used EMI-137 (a c-Met-targeted fluorescent peptide) in high-risk populations of colorectal cancer to determine the optimal dose-imaging interval and safety of FME. Methods: We performed FME and fluorescence quantification in 15 patients with dysplastic colorectal adenoma by multi-diameter single fiber reflectance/single fiber fluorescence spectroscopy. EMI-137 was administered intravenously (0.13 mg/kg) at 1-hour, 2-hour, or 3-hour dose imaging intervals (n = 3 patients per group). Based on the target to background ratio, the two cohorts were expanded to 6 patients. Fluorescence is related to histopathology and c-Met expression. The binding specificity of EMI-137 was evaluated by fluorescence microscopy and in vitro experiments. Results: FME using EMI-137 appears to be safe and well tolerated. All dose imaging intervals showed that the fluorescence in colorectal lesions was significantly higher than that in surrounding tissues. The target-to-background ratios of the 1, 2 and 3 hour cohorts were 1.53, 1.66, and 1.74, respectively, and the average intrinsic fluorescence was 0.035 vs. 0.023 mm-1 ( P <0.0003), 0.034 vs. 0.021 mm-1 (P <0.0001), and 0.033 vs. 0.019 mm-1 (P <0.0001). Fluorescence is related to histopathology at the macro and micro level, and is significantly overexpressed in dysplastic mucosa c-Met. In vitro, dose-dependent specific binding was confirmed. Conclusion: FME using EMI-137 seems to be safe and feasible in the 1 to 3 hour dose to imaging interval. Although from a clinical point of view, the 1-hour dose to imaging interval is the first choice, no clinically significant differences were observed in the cohort. Future studies will investigate EMI-137 to improve colorectal polyp detection during colonoscopy.
Most colorectal cancers develop through the sequence from adenoma to carcinoma (1). Therefore, early detection of precancerous polyps, such as adenomas and sessile serrated polyps, can improve the prognosis of patients (2). So far, the gold standard for detection of precancerous lesions is high-definition white light endoscope (HD-WLE). Although HD-WLE has made a significant contribution to the success of screening and preventing colorectal cancer, it also has limitations (3,4). Inadequate bowel preparation and the lack of skills and expertise of endoscopists may lead to reduced sensitivity, leading to a missed diagnosis rate of adenoma in the general population as high as 22% and as high as 55% in Lynch syndrome patients (5,6) Certain locations (ie ascending colon) and morphological features of adenomas, such as small size (ie less than 10 mm) or flat shape, are notorious for their high missed detection rate (7).
These factors emphasize the need for a novel imaging technique to reduce the high detection error rate. Fluorescent molecular endoscopy (FME) administers targeted fluorescent tracers that can visualize specific markers that are overexpressed on the target of interest. Combining HD-WLE technology with FME to display morphological mucosal abnormalities to show the real-time biological characteristics of cells may increase the detection rate of polyps (8-10).
In the colorectal adenoma-to-carcinoma sequence, one of the markers that is significantly overexpressed as the degree of dysplasia progresses is c-Met (11). c-Met is a receptor tyrosine kinase that can bind to its ligand hepatocyte growth factor and activate several downstream signaling pathways involved in proliferation, movement, migration and invasion (11,12). The fluorescently labeled peptide EMI-137 (previously known as GE-137) is a water-soluble 26 amino acid cyclic peptide that can specifically bind to human c-Met with high affinity (8). Its peak excitation and emission wavelengths are 653 and 675 nm, respectively. It has good pharmacokinetic properties, can achieve rapid tissue biodistribution, and has a background clearance half-life of approximately 2 hours and 30 minutes.
Previously, intravenous injection of EMI-137 3 hours before colonoscopy showed that it is possible to detect other polyps that were initially missed by traditional fiber-based white light colonoscopy (8). In order to expand the clinical applicability of EMI-137 to future phase II or phase III trials, we have determined the optimal dose imaging interval for the parallel detection of colorectal polyps using FME and HD-WLE, and used multi-diameter single fiber reflection to quantify fluorescence/single Optical fiber fluorescence (MDSFR/SFF) spectrum. In addition, in a group of patients who are strongly suspected of having colorectal cancer, the safety and tolerability of EMI-137 were studied.
The study was approved by the Beoordeling Ethiek Biomedisch Onderzoek ethics committee. All patients gave written informed consent. If patients are over 18 years of age and plan to undergo diagnostic or therapeutic endoscopy to treat colorectal adenomas with at least low-grade dysplasia, they are eligible to participate in the study. Female patients must be surgically infertile, have a negative urine pregnancy test after menopause or before menopause. The study was registered in the European Clinical Trial Registry (2016-002827-27) and was conducted at the University of Groningen Medical Center from October 2017 to September 2018 in accordance with the Declaration of Helsinki.
1, 2 or 3 hours before endoscopy, EMI-137 was administered as a single intravenous bolus injection of 0.13 mg/kg of 4.8 mg/mL solution, initially with 3 patients in each group (Figure 1). After standard bowel preparation, all endoscopic surgeries were performed by a board-certified gastroenterologist using a clinical high-definition video endoscope (CF-HQ190 L/I, Evis Exera III; Olympus Corp.). Treatment includes segmented polypectomy, endoscopic mucosal resection, endoscopic submucosal dissection, or endoscopic full-thickness resection, depending on the location, size, and characteristics of the lesion. The 650 nm short-pass filter (Chroma Technology Corp.) is installed in the Olympus xenon light source (CLV-190, Evis Exera III) to prevent accidental excitation of EMI-137.
Research the workflow. (A) EMI-137 is administered intravenously (0.13 mg/kg). (B) After 1, 2 or 3 hours, perform real-time FME and in vivo MDSFR/SFF spectroscopy. Each cohort included 3 patients, which was expanded to 6 patients in the 1-hour and 2-hour cohorts based on the results of the interim analysis.
Use SurgVision Endoscope Explorer (SurgVision BV) to observe fluorescence in vivo, a real-time fluorescence imaging system connected to a flexible fiberscope that can be inserted through a clinical high-definition video endoscope. SurgVision Endoscope Browser is composed of a white light emitting diode and 2 class III-b lasers optimized for EMI-137 visualization (excitation wavelength, 653 nm), which can simultaneously generate white light, fluorescence and superimposed images.
During FME, according to the consensus of gastroenterologists and researchers, the visibility of adenomas is qualitatively described as "significantly increased", "slightly increased", or "same as background" compared to surrounding normal tissues. In order to confirm the results of visualized fluorescence imaging in vivo, MDSFR/SFF spectroscopy is then used to quantify the fluorescence intensity in vivo. This is an optical technique that can correct the influence of tissue optical properties, so that the intrinsic fluorescence value of EMI-137 can be determined (Figure 2). 2A). In short, by directly contacting the MDSFR, insert another fiber bundle to determine the tissue absorption coefficient and reduced scattering coefficient at the excitation wavelength (650 nm) and the emission band of the fluorophore cyanine-5** (600–800 nm) Measurement. Subsequently, the SFF spectrum was obtained. After the clinical procedure, the intrinsic fluorescence value (10,13-15) of cyanine-5** in EMI-137 was calculated.
MDSFR/SFF spectrum. (A) Schematic diagram of the equipment. (B) The individual intrinsic fluorescence values of the adenoma and surrounding normal tissues of each time group (left y axis), and the average target to background (TBR) ratio (red; right y axis). The histological grades of adenomas are low-grade dysplasia (LGD; gray), high-grade dysplasia (HGD; blue), and adenocarcinoma (adenocarcinoma; orange). Error bars indicate mean ± SD.
According to the length of the endoscopy procedure, multiple FME and MDSFR/SFF spectral measurements are taken every 30 minutes for each lesion and surrounding normal tissues. If the in vivo MDSFR/SFF spectrum measurement value cannot be obtained due to the location of the lesion (the fiber bundle cannot be reversed), the measurement value is directly obtained in vitro after the resection.
Monitor vital signs, injection sites, and occurrence of serious adverse events based on common toxicity criteria for adverse events at routine time points. After the administration of EMI-137, a follow-up period of up to 24-48 hours was carried out.
According to the availability and quality of the images, the area of interest of the lesion and surrounding normal colorectal tissues is depicted on 1-4 representative white light images of each patient, with approximately the same distance from the fibers. Subsequently, the Fiji/ImageJ software (version 2.0.0-rc-68/1.52h) was used to calculate the mean fluorescence intensity (MFI) as the total count for each pixel area of interest. The MFI of the disease is divided by the MFI of the surrounding normal tissue to determine the TBR. In addition to FME analysis (ie TBR calculation based on MFI of in vivo FME images), we also evaluated in vivo quantitative MDSFR/SFF spectral data (ie TBR calculation based on quantitative intrinsic fluorescence values).
An interim analysis was performed after the first 9 patients to assess EMI-137 safety data and use FME and MDSFR/SFF spectra to determine the TBR of each cohort. The 2 cohorts with the best TBR were expanded to 6 patients in each cohort. If the TBRs of all three cohorts are comparable, the 1-hour and 2-hour cohorts will be expanded to 6 patients in each cohort, because from a clinical point of view, shorter dose imaging intervals are preferred.
After the resection, histopathological processing and examination are performed by a board-certified gastrointestinal pathologist who does not know the results of fluorescence imaging according to the standard clinical protocol of the University of Groningen Medical Center.
Based on the quality of the slices and the coexistence of dysplasia and surrounding normal crypts, each patient selects up to four 4 micron tissue slices for further analysis. After xylene deparaffinization, the tissue sections were air-dried and scanned using Odyssey CLx fluorescence scanner (LI-COR Biosciences Inc.), and then directly stained with hematoxylin and eosin to achieve precise correlation between fluorescence and histology. MFI is measured as the total count of the pixel area of each region of interest of the dysplastic mucosa and surrounding normal mucosa based on histological description of the pathologist.
According to the standard clinical protocol of the University of Groningen Medical Center, the BenchMark Ultra system (Ventana Medical Systems) was used to perform c-Met immunohistochemistry with SP44 rabbit monoclonal primary antibody against membrane and cytoplasmic c-Met epitopes. Pathologists semi-quantitatively scored the local staining intensity of the dysplasia and surrounding normal colorectal mucosa as negative (0), weak (1), moderate (2) or strong (3). A score of 2/3 is considered positive for c-Met overexpression.
As mentioned earlier (15,16), fluorescence microscopy was performed on a representative 4-μm tissue section of each patient to assess the accumulation of EMI-137 at the microscopic level. The DM6000 fluorescence microscope is used in combination with the DFC360FX camera (Leica Biosystems GmbH), and the magnification setting is the same each time (cyanine-5;ie, EMI-137) filter cube.
Several in vitro experiments were performed on the high c-Met overexpression cell line (HT-29) and the c-Met negative cell line (SW-480) to confirm the specificity of EMI-137 binding (described in the supplementary material , Available from http://jnm.snmjournals.org) (17).
Descriptive statistics are applied to patient demographics. Normally distributed data is expressed as the mean of SD, and Student's t test (paired data) is used to test significance. Non-normally distributed data is expressed as a median with interquartile range (IQR), and the Wilcoxon (paired data) or Mann-Whitney U (independent data) test is used to test for significance. P values less than 0.05 are considered statistically significant. Use GraphPad Prism (version 8.0; GraphPad Software Inc.) for statistical analysis and graphic design.
A total of 19 patients signed the written informed consent and accepted the study participation screening, of which 16 were eligible for inclusion. The average age is 62 years (range 59-73 years; Table 1). All 16 patients received an intravenous bolus of EMI-137 at 0.13 mg/kg. Fourteen patients received the expected treatment procedures (3 segmented polypectomy, 4 endoscopic mucosal resection, 6 endoscopic submucosal dissection, and 1 endoscopic full-thickness resection), and 1 patient received Diagnostic procedure, colonoscopy of 1 patient due to patient's discomfort. Histological evaluation of the resected lesions revealed all tubular adenomas with at least low-grade dysplasia. Five tubular adenomas (31.2%) had high-grade dysplasia, and three other lesions (18.8%; Table 1) had adenocarcinoma.
After EMI-137 was administered in any patient, no clinically significant changes in vital signs were observed, and there were no skin abnormalities at the injection site. A possibly related grade 1 adverse event (hypotension after anesthesia) and a possibly related grade 2 adverse event (mild allergic reaction, several hours after EMI-137 administration) were observed. Two serious adverse events occurred; both were iatrogenic perforations of the large intestine and were considered not to be related to EMI-137 or any research-related procedures, but to therapeutic endoscopy procedures (endoscopy The perforation of the sigmoid colon during the layer resection and the perforation of the rectum during the repeated endoscopic submucosal dissection in this area are related to the previous endoscopic mucosal resection).
FME was performed in 15 of the 16 patients. In one patient, the cecal polyp could not be touched due to the patient's discomfort, and the endoscopy was terminated prematurely. The patient later underwent polypectomy under propofol sedation and was replaced in the study. The planned interim analysis after enrollment of the first 9 patients showed that the TBR of all three time intervals measured by FME images and MDSFR/SFF spectra were comparable. The 1-hour and 2-hour cohorts were expanded to 6 patients, respectively, because of the clinical preference for shorter dose imaging intervals.
The interval from dose to imaging in the 1-hour cohort was 0:54–1:28 hours, the 2-hour cohort was 1:50–2:33 hours, and the 2-hour cohort was 2:41–3:20 hours. 3 hour queue. A total of 15 patients found 16 lesions during endoscopy. The estimated median adenoma size during colonoscopy was 3.0 cm (range, 1.5-5.5 cm). In vivo qualitative assessment of fluorescence increased significantly in 5 out of 16 adenomas (31%), slightly increased in 8 out of 16 (50%), and compared with 3 out of 16 (19%) The background is the same, based on FME images. Three lesions evaluated as having the same fluorescence as the background can be identified using fluorescence because of their morphological characteristics. A representative FME image is shown in Figure 3.
Representative FME images of lesions with surrounding normal tissue for each cohort. The columns from left to right are HD-WLE images (Olympus CF-HQ 190 L/I) and white light, fluorescence and overlay images (SurgVision Endoscope Explorer [SVEE]). The histological grades from top to bottom were adenocarcinoma, adenocarcinoma, and low-grade dysplasia.
A total of 74 representative FME images obtained from 16 lesions at different time points were analyzed to determine the TBR for each time interval. Compared with the surrounding normal colorectal tissue, all lesions showed enhanced fluorescence. The median TBR at 1, 2, and 3 hours were 2.18 (IQR, 0.87), 1.62 (IQR, 0.51), and 1.43 (IQR, 0.75) Dose imaging interval, respectively (Figure 4).
The median TBR of the FME image and MDSFR/SFF spectral data of each time group. The histological grades of adenomas are low-grade dysplasia (LGD; gray), high-grade dysplasia (HGD; blue), and adenocarcinoma (adenocarcinoma; orange). Error bars indicate median ± IQR (FME TBR) and mean ± SD (MDSFR/SFF Spectral TBR).
In addition to FME TBR, a post-processing algorithm was used to analyze the in vivo direct contact MDSFR/SFF spectroscopy measurement, and the intrinsic fluorescence value was quantified by correcting the optical characteristics of 14 of the 16 lesions. The MDSFR/SFF spectrum measurement of the remaining 2 lesions was performed directly in vitro after adenoma resection, because in vivo measurement is not feasible due to technical reasons. For the 1-hour cohort (0.035 ± 0.0023 versus 0.023 ± 0.0024 mm-1, P <0.0003), the 2-hour cohort (0.034 ± 0.0020 versus 0.0020 ± 0 0.0014 mm-1, P <0.0001) and the 3-hour cohort (0.033 ± 0.0023 versus 0.019 ± 0.0023 mm-1, P <0.0001; Figure 2B). From 1 hour to at least 3 hours, the quantitative fluorescence values in the adenoma remain consistent. In contrast, a slight downward trend in quantitative fluorescence values was observed in normal colorectal tissues (Figure 2B). Therefore, the spectral TBR increased slightly over time, and the average TBR for the 1, 2 and 3 hour cohorts were 1.53 ± 0.21, 1.66 ± 0.07, and 1.74 ± 0.16 (Figure 2B, right axis).
When comparing FME TBR with MDSFR/SFF spectral TBR, no statistically significant difference was observed, except for the 1-hour cohort, where FME TBR was higher than MDSFR/SFF spectral TBR (2.18 vs. 1.54, P = 0.038; Figure 4 ). The MDSFR/SFF spectrum values corrected for tissue scattering and absorption coefficients show smaller changes than the FME image values.
The correlation between fluorescence intensity, histology and c-Met expression was further evaluated in vitro. According to the in vivo results, on the 4 μm tissue sections of each cohort, the dysplastic or cancerous mucosa showed a significant increase in fluorescence compared with the surrounding normal mucosa. The median TBR was 1.69 (IQR, 0.49; P = 0.0398), 1.43 ( The IQR for the 1, 2 and 3 hour cohorts were 0.37; P = 0.0020) and 1.46 (IQR, 0.16; P = 0.0156) (Figure 5A).
In vitro verification of EMI-137 fluorescence. (A) The correlation between the average fluorescence intensity of adenoma (Dyspl.) and surrounding normal tissues (Norm.) and the histology of 4 μm tissue sections (n = 35), with median ± IQR (left y axis) and middle Value TBR (right y-axis; red). (B) c-Met membrane expression is related to histology, 0 = negative, 1 = weak, 2 = moderate, 3 = strong membrane expression. (C) Fluorescence microscopy of dysplasia (left) and normal colorectal tissue (right) (40x magnification; 4',6-diamidino-2-phenylindole/Hoechst nuclear staining [blue]; different Fluorescein thiocyanate [FITC]/autofluorescence [green] and cyanine-5 [Cy5]/EMI-137 derived fluorescence [red]).
c-Met immunohistochemical analysis showed that the dysplastic mucosa had moderate (2, 72.2%) to strong (3, 27.8%) membrane overexpression, while the normal colorectal mucosa showed negative (0, 53.8%) to weak (1, 46.2%) Physiological membrane staining (Figure 5B).
Finally, compared with surrounding normal colorectal crypts, fluorescence microscopy showed an increase in the fluorescence intensity of abnormal hyperplasia or cancerous colorectal crypts (Figure 5C). The fluorescent signal is clearly concentrated near the cell membrane of dysplastic cells. The surrounding normal tissues show significantly lower fluorescence intensity with more matrix localization.
In order to further study the binding specificity of EMI-137, in vitro experiments were carried out. Immunohistochemistry and Western blotting confirmed c-Met expression in HT-29 cells and minimal c-Met expression in SW-480 cells. Fluorescence microscopy revealed EMI-137-derived fluorescence on the surface of HT-29 cells, while the fluorescence level of SW-480 cells was negligible (Supplementary Figures 1A and 1B). Compared with SW-480 cells, flow cytometry analysis confirmed the dose-dependent membrane binding of EMI-137 in HT-29 cells. This finding was supported by the c-Met receptor saturation experiment using EMI-137 and a non-fluorescent unlabeled peptide (AH111972), which showed blocking of c-Met receptor, therefore, it was only visible in HT-29 cells. This reduces the MFI (Supplementary Fig. 1C).
In this study, we demonstrated that the use of 0.13 mg/kg of EMI-137 FME at a dose of 0.13 mg/kg at 1, 2, or 3 hours before colonoscopy appears to be safe and feasible for the detection of colorectal polyps. In vivo FME results were confirmed by using MDSFR/SFF spectroscopy to quantify intrinsic fluorescence. In each time interval, the fluorescence in all lesions was significantly higher than the surrounding normal colorectal tissue. Based on extensive in vivo and in vitro analyses, no clinically significant differences were observed between the time groups studied. Therefore, we have concluded that FME using EMI-137 can be performed in a time range of 1 to 3 hours, thereby extending the clinical applicability of EMI-137.
The use of FME as a dangerous endoscopic imaging technique to improve polyp detection has been previously studied using different fluorescent tracers, although several factors hinder further clinical translation (9,10). First, bevacizumab-800CW, a near-infrared fluorescent tracer targeting vascular endothelial growth factor-A (peak emission, 792 nm), has unfavorable pharmacokinetics and requires a dose imaging interval of 2-3 days. Application of screening population for rectal cancer (10). Secondly, the fluorescent peptide KCC*-fluorescein isothiocyanate (peak emission, 519 nm) binds to sessile serrated adenoma, which has a V600E point mutation in BRAF and is evaluated using post-processing software. However, the demand for post-processing software limits the real-time lesion recognition parallel to HD-WLE (9). In addition, the fact that KCC*-fluorescein isothiocyanate has a peak emission in the visible light spectrum may reduce imaging specificity because it has a lower penetration depth and is increasingly affected by near-infrared fluorescence imaging. The effect of autofluorescence. In addition to intravenous administration, local tracer administration was also evaluated during colonoscopy, although local administration rarely achieves complete mucosal coverage, and the binding of tracers is affected by the adequacy of intestinal preparation. Influence (18). In order to overcome these limitations, we used a near-infrared fluorescent peptide with a relatively low molecular weight, which has good pharmacokinetic properties and can identify adenomas within 1 to at least 3 hours after intravenous administration.
In order to determine the optimal dose imaging interval, fluorescence quantification is important in early clinical FME trials, because only the fluorescence intensity observed by FME is affected by tissue optical characteristics and technical factors (such as camera sensitivity, imaging distance, and illumination). 19). Add MDSFR/SFF spectroscopy as a verification technique to provide objective and consistent intrinsic fluorescence values through direct contact measurements. These measurements are corrected for tissue scattering and absorption coefficients (10,13–15). The importance of using MDSFR/SFF spectroscopy was emphasized in the qualitative assessment of 3 adenomas with the same fluorescence as during FME, and MDSFR/SFF spectroscopy measurements showed significant differences in intrinsic fluorescence values. Although MDSFR/SFF spectrum measurement is currently calculated using post-processing algorithms, the results of this study further support the development of MDSFR/SFF spectrum measurement as a supplementary technology for FME.
Consistent with the literature, our immunohistochemical analysis confirmed that c-Met is indeed a suitable marker for the detection of colorectal adenomas, because we have observed significant membrane overexpression of c-Met in dysplasia and cancerous mucosa (11,12 ). Although the overexpression of c-Met in adenomas is heterogeneous, it does not affect the results of macroscopic fluorescence imaging (Figure 5). The fluorescence intensity visualized and quantified in vivo remained consistent over time, indicating the specific binding of EMI-137. In addition, the quantified intrinsic fluorescence value did not appear to increase further after 1 hour (Figure 2B), indicating that the current dose of 0.13 mg/kg has saturated the available c-Met receptor 1 hour after administration. Interestingly, the background fluorescence level decreased slightly over time, which may be caused by the elimination of unbound EMI-137 (elimination half-life, ~2h30m) (8). Lower tracer doses may further reduce background fluorescence while still saturating the available c-Met receptors, which may enhance TBR and increase sensitivity.
So far, there has not been an integrated video endoscope that can realize high-sensitivity near-infrared fluorescence imaging in parallel with HD-WLE. We applied a near-infrared fluorescence endoscope system with clinical application potential, because the fiber-based SurgVision Endoscope Explorer can realize HD-WLE and FME at the same time. This use requires a short-pass filter to be installed in the standard Olympus white light source; due to the overlap with the excitation spectrum of EMI-137, this filter can prevent the Olympus white light source from being excited by EMI-137. The SurgVision Endoscope Explorer fiber probe is composed of 10,000 fibers, which provides sufficient resolution for the current research design to co-localize the fluorescence intensity to the HD-WLE image. However, increasing the number of fibers to 30,000 will improve the quality of white light images and promote further clinical transformation of EMI-137 during colonoscopy (10,15,16). In addition, the red laser can be seen on the HD-WLE image of the clinical video endoscope, which affects the quality of the HD-WLE image. This phenomenon has not been described before with bevacizumab-800CW, which is a fluorescent tracer that can further emit fluorescence in the near-infrared spectrum (10,15,16). Alternatively, installing a short-pass filter or pulse collection at the tip of the endoscope can also prevent the interference of the red laser during HDWLE.
In this study, FME was used to visualize fluorescence during endoscopy, and MDSFR/SFF spectroscopy was used to quantify intrinsic fluorescence by correcting the optical properties of tissues. Ultimately, clinicians need a technology that provides real-time objective information, preferably by combining these methods in the body to reliably guide the endoscopist during colonoscopy.
Since the purpose of this study is to determine the optimal dose imaging interval for EMI-137, only patients with advanced adenoma detected during previous colonoscopy were included. As a result, a complete colonoscopy was not performed. In addition, our study population may not be representative of the screening population with an average risk of developing colorectal cancer. Although our cohort is relatively small, the 3 3 study design is a commonly used method to obtain information about the dose or timing of new compounds while limiting the number of exposed patients (20). Future research will need to determine whether EMI-137 can indeed increase the current adenoma detection rate in the larger general screening population.
The study shows that from 1 hour to at least 3 hours of dose imaging interval, the use of EMI-137 FME seems to be safe and feasible. Ultimately, there may be a trade-off between maintaining sufficient TBR for lesion detection and clinically acceptable imaging dose intervals. Our data supports further research on the potential benefits of EMI-137 within this time frame of phase II or phase III clinical trials to investigate the potential improvement in polyp detection rates in the general screening population.
Wouter Nagengast received an unlimited research grant from SurgVision BV (Groningen, Netherlands). The research was funded by Edinburgh Molecular Imaging Ltd (EMI) in Edinburgh, UK. The funders of the study had no influence on data collection, analysis or interpretation, or the writing of the manuscript. The corresponding author has full access to all data and is ultimately responsible for the decision to submit for publication. No other potential conflicts of interest related to this article have been reported.
Question: When using c-Met targeting fluorescent peptide EMI-137 to detect colorectal polyps, what is the optimal dose imaging interval for FME?
Related findings: In this clinical trial, we showed that fluorescence-based in vivo visualization using EMI-137 FME to detect colorectal adenomas within 1 to 3 hour dose imaging interval seems to be safe and feasible, by correcting the optical properties of the tissue And extensive in vitro verification to quantify fluorescence in vivo.
Impact on patient care: Our research results expand the dose-imaging window for clinical application of EMI-137 and support further research on EMI-137 within this time frame to improve polyp detection in the general screening population Rate.
We would like to thank the patients and senior laboratory analyst Gert Jan Meersma who participated in the clinical research for conducting in vitro experiments.
↵* Make equal contributions to this work.
↵† Contribute equally to this work.
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