PET imaging of EGFR expression using an 18 F-labeled RNA aptamer

Abstract

Objective

Epidermal growth factor receptor (EGFR) is a theranostic biomarker for a variety of cancer types. The aim of the present study was to develop an ¹⁸F radiolabeled EGFR targeting RNA aptamer, and to investigate its ability to visualize and quantify EGFR in xenograft models.

Methods

Biolayer interferometry binding assay was used to detect the binding affinity of the alkyne-modified EGFR aptamer MinE07 (denoted as ME07) with recombinant human wild-type EGFR protein and the mutant EGFRvIII protein. Cy5-conjugated ME07 was used for flow cytometry and immunofluorescence staining, and an Alexa Fluor 488-labeled EGFR antibody (ab193244) was used as a control. ¹⁸F-Fluorobenzoyl (FB) azide was employed as a synthon to produce ¹⁸F-FB-ME07 via click chemistry, and the cellular uptake and internalization characteristics of ¹⁸F-FB-ME07 were investigated. Static PET scans, 60-min dynamic scans, and biodistribution study of ¹⁸F-FB-ME07 were performed in three types of tumor models.

Results

The K_d values of ME07 to wtEGFR and EGFRvIII proteins were 0.3 nM and 271 nM respectively. The A431, U87MG, and HCT-116 cells showed strong, weak, and negative binding with Cy5-ME07, which is consistent with EGFR expression level in these cells. Peak cell uptake values of ¹⁸F-FB-ME07 in A431, U87MG and HCT-116 cells were 2.86%, 2.19% and 0.88% of the added dose respectively. The mean internalization of ¹⁸F-FB-ME07 in these cells were 60.02%, 53.1%, and 52.8% of the total accumulated radioactivity. In static PET imaging, despite high uptake in the liver and kidneys, ¹⁸F-FB-ME07 showed reasonable accumulation in A431 tumors (1.02 ± 0.13 %ID/g at 30 min after injection). Of note, the uptake of ¹⁸F-FB-ME07 in A431 xenografts was significantly higher than that in U87MG and HCT-116 xenografts. In A431 xenografted mice, the tumor/blood ratio was 3.89 and the tumor/muscle ratio reached 8.65.

Conclusions

We for the first time generated an aptamer-derived EGFR targeting PET tracer ¹⁸F-FB-ME07, which showed highly selective targeting ability in mouse tumor models expressing different levels of EGFR. Our results suggest that ¹⁸F-FB-ME07 is a potential EGFR targeting molecular imaging probe for future clinical translation.

https://ift.tt/2mZiumd

The hi-tech way to handle the new gen kind in the procedure room

Publication date: Available online 1 August 2018

Source: Journal of the American Academy of Dermatology

Author(s): K.T. Ashique, Feroze Kaliyadan

https://ift.tt/2OtERNf

FIMARAD : la filière de santé maladies rares en dermatologie

Publication date: Available online 31 July 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): C. Bodemer, C. Taïeb, D. Vidaud, S. Ingen-Housz-Orob, R. Gène

https://ift.tt/2OwCI3b

A Fast and Reliable Noise-Resistant Medical Image Segmentation and Bias Field Correction Model

Publication date: Available online 1 August 2018

Source: Magnetic Resonance Imaging

Author(s): Yunyun Yang, Dongcai Tian, Boying Wu

Abstract

In recent years, with the rapid development of modern medical image technology, the medical image processing technology is becoming more important. In particular, the accurate segmentation of medical images is significant for doctors to diagnose and analyze the etiology. However, the false contours appearing in medical images due to fuzzy image boundary, intensity inhomogeneity and random noise, may lead to the inaccurate segmentation results. In this paper, an improved active contour model based on global image information is proposed, which can accurately segment images disturbed by intensity inhomogeneities and serious noise. We give the two-phase energy functional and multi-phase energy functional of our model, and apply it to segment magnetic resonance (MR) images, ultrasound (US) images and synthetic images. Experimental results and comparisons with other models have shown that our model has the advantages of higher accuracy, higher efficiency and robustness in dealing with the intensity inhomogeneity and serious noise in image segmentation.

https://ift.tt/2LRkqLK

Assessing severity of anaphylaxis: a data-driven comparison of 23 instruments

The severity of an allergic reaction can range from mild local symptoms to anaphylactic shock. To score this, a number of instruments have been developed, although heterogeneous in design and purpose. Severity...

https://ift.tt/2mYwuMS

Bioactivity of diatomaceous earth against the subterranean termite Reticulitermes chinensis Snyder (Isoptera: Rhinotermitidae)

Abstract

The effects of diatomaceous earth (DE) on the penetrating behavior, tunneling behavior, mortality, and body surface characteristics of the subterranean termite Reticulitermes chinensis were investigated in this study. Our results show that the workers of R. chinensis were able to penetrate 1- and 2-mm layers of dry DE but not 3-mm layers. After treatment with dry DE for 6 h, the mortality of termites reached 100%, which was significantly higher than in the treatment with DE with a 10 and 25% moisture content and treatment with sand of three different moisture contents. The tunneling distances of workers in DE with 10, 25, and 50% moisture contents were all significantly shorter than those in sand with the same moisture contents (10, 25, and 50%), indicating that DE has a good suppressing effect on the tunneling behavior of workers. After treatment with dry DE for different times (1, 3, and 6 h), many DE particles adhered to the bodies of workers, whereas no particles adhered to the body of workers in the case of treatment with dry sand. The treatment with dry DE for 6 h resulted in the death of all workers, which presented conspicuous abdominal shrinkage, whereas workers treated with sand had no significant mortality and no obvious abdominal shrinkage. In summary, we suggest that dry DE has ideal insecticidal activity against the subterranean termite R. chinensis and can be further exploited for controlling termites inside houses.

https://ift.tt/2LJmwha

Case report: Long-term survival of a pancreatic cancer patient immunized with an SVN-2B peptide vaccine

Abstract

A 62-year-old woman who underwent surgery to treat pancreatic cancer provided written, informed consent to undergo adjuvant therapy with gemcitabine, tegafur, and uracil. However, this was stopped after only 14 days due to Grade 4 neutropenia. She was then started on vaccine therapy with Survivin 2B peptide (SVN-2B) including IFA and INF-α. Although metastatic lung tumors were identified and resected at 82 months after surgery, the patient has remained free of new or relapsed disease for 12 years thereafter. Tetramer and ELISPOT assays revealed the continuous circulation of SVN-2B-restricted cytotoxic T-lymphocytes (CTLs) in her peripheral blood, and CTL clones had specific activity for SVN-2B at 12 years after surgery. The adverse effects of the peptide vaccination were tolerable and comprised low-grade headache, nausea, and fatigue. A prognosis beyond 10 years in the face of pancreatic cancer with distant metastasis is extremely rare. This experience might indicate the value of cancer vaccination therapy.

https://ift.tt/2Kf8yyj