Dataset Information

PET of HER2-positive pulmonary metastases with 18F-ZHER2:342 affibody in a murine model of breast cancer: comparison with 18F-FDG.

ABSTRACT: UNLABELLED:Targeted therapies often depend on the expression of the target present in the tumor. This expression can be difficult to ascertain in widespread metastases. (18)F-FDG PET/CT, although sensitive, is nonspecific for particular tumor markers. Here, we compare the use of a human epidermal growth factor receptor 2 (HER2)-specific (18)F-Z(HER2)(:342)-Affibody and (18)F-FDG in HER2-expressing pulmonary metastases in a murine model of breast cancer. METHODS:The lung metastasis model was established by intravenous injection of MDA-MB-231(HER2)-Luc human breast cancer cells into the tail vein. Bioluminescence imaging was used to evaluate metastasis progression. Uptake of (18)F-Z(HER2)(:342)-Affibody and (18)F-FDG was confirmed by coregistration of the PET images with MR and CT images. At the end of the study, the presence of neoplastic cells and HER2 expression in lung tissues, and distribution of the tracer, were assessed ex vivo by immunohistochemistry and autoradiography. RESULTS:(18)F-Z(HER2)(:342)-Affibody successfully targeted HER2-positive lesions in the lung and allowed detection of metastases as early as 9 wk after injection of cells. In contrast, (18)F-FDG uptake was often masked by surrounding inflammatory changes and was nonspecific for HER2 expression. HER2 expression at a cellular level correlated well with tracer uptake on autoradiography. CONCLUSION:(18)F-Z(HER2)(:342)-Affibody is a promising tracer for evaluation of HER2 status of breast cancer metastases and is more specific for detecting HER2-positive lesions than (18)F-FDG.

SUBMITTER: Kramer-Marek G

PROVIDER: S-EPMC7497802 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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PET of HER2-positive pulmonary metastases with 18F-ZHER2:342 affibody in a murine model of breast cancer: comparison with 18F-FDG.

Kramer-Marek Gabriela G Bernardo Marcelino M Kiesewetter Dale O DO Bagci Ulas U Kuban Monika M Aras Omer O Zielinski Rafal R Seidel Jurgen J Choyke Peter P Capala Jacek J

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20120511 6

<h4>Unlabelled</h4>Targeted therapies often depend on the expression of the target present in the tumor. This expression can be difficult to ascertain in widespread metastases. (18)F-FDG PET/CT, although sensitive, is nonspecific for particular tumor markers. Here, we compare the use of a human epidermal growth factor receptor 2 (HER2)-specific (18)F-Z(HER2)(:342)-Affibody and (18)F-FDG in HER2-expressing pulmonary metastases in a murine model of breast cancer.<h4>Methods</h4>The lung metastasis ...[more]

PMID: 22582046

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Project description:Positron lymphography using 18F-FDG followed by Cerenkov-guided resection of lymph nodes in healthy mice has previously been introduced by our group. Our aim in this study was to further assess the technique's potential beyond merely localizing sentinel lymph nodes. We now aimed to evaluate the potential of positron lymphography to characterize the nodes with respect to their tumor status in order to identify metastatic lymph nodes. We explored whether metastatic nodes could be distinguished from normal nodes via dynamic 18F-FDG lymphography, to then be resected under Cerenkov imaging guidance. Methods: A murine melanoma cell line highly metastatic to lymph nodes (B16F10) was implanted subcutaneously on the dorsal hind paw of C57 mice while the tumor-free contralateral leg served as an intraindividual control. A model of reactive lymph nodes after concanavalin A challenge served as an additional control to provide nonmalignant inflammatory lymphadenopathy. Dynamic PET/CT imaging was performed immediately after injection of 18F-FDG around the tumor or intracutaneously in the contralateral footpad. Furthermore, PET/CT and Cerenkov studies were performed repeatedly over time to follow the course of metastatic spread. In selected mice, popliteal lymph nodes underwent Cerenkov luminescence imaging. Hematoxylin and eosin staining was done to verify the presence of lymphatic melanoma infiltration. Results: Positron lymphography using 18F-FDG was successfully performed on tumor-bearing and non-tumor-bearing mice, as well as on controls bearing sites of inflammation; the results clearly identified the sentinel lymph node basin and delineated the lymphatic drainage. Significantly prolonged retention of activity was evident in metastatic nodes as compared with controls without tumor. On the basis of these results, the contrast in detection and identification of metastatic lymph nodes was distinct and could be used for guided lymph node resection, such as by using Cerenkov luminescence imaging. However, retention after 18F-FDG lymphography was also seen in acute inflammatory lymphadenopathy. Conclusion: In a tumor model, significantly longer retention of the radiotracer during 18F-FDG lymphography was seen in metastatic than nonmetastatic lymph nodes, allowing for differentiation between the two and for selective resection of tumor-bearing nodes using Cerenkov imaging. Inflammation can be better differentiated in a subacute state.

Project description:UnlabelledEpidermal growth factor receptor (EGFR) is often overexpressed in a variety of human cancers, and its expression is associated with poor prognosis for many cancer types. However, an accurate technique to noninvasively image EGFR expression in vivo is not available in the clinical setting. In this research, an Affibody analog, anti-EGFR Ac-Cys-Z(EGFR:1907), was successfully site-specifically (18)F-labeled for PET of EGFR expression.MethodsThe prosthetic group N-[2-(4-(18)F-fluorobenzamido) ethyl] maleimide ((18)F-FBEM) was conjugated to Ac-Cys-Z(EGFR:1907) under mild conditions (pH 7) to produce the probe (18)F-FBEM-Cys-Z(EGFR:1907). The binding affinity and specificity tests of (18)F-FBEM-Cys-Z(EGFR:1907) to EGFR were conducted using A431 cancer cells. Small-animal PET and biodistribution studies were conducted on various mice tumor xenograft models with EGFR overexpression (6 types) after injection of approximately 2.0 MBq of (18)F-FBEM-Cys-Z(EGFR:1907) with or without coinjection of unlabeled Ac-Cys-Z(EGFR:1907) for up to 3 h after injection. A correlation study between (18)F-FBEM-Cys-Z(EGFR:1907) small- animal PET quantification and ex vivo Western blot analysis of tumor EGFR expression was conducted in those 6 types of tumor models.Results(18)F-FBEM-Cys-Z(EGFR:1907) binds to EGFR with low nanomolar affinity (37 nM) in A431 cells. (18)F-FBEM-Cys-Z(EGFR:1907) rapidly accumulated in the tumor and cleared from most of the normal organs except the liver and kidneys at 3 h after injection, allowing excellent tumor-to-normal tissue contrast to be obtained. In the A431 tumor xenograft model, coinjection of the PET probe with 45 μg of Ac-Cys-Z(EGFR:1907) was able to improve the tumor uptake (3.9 vs. 8.1 percentage of the injected radioactive dose per gram of tissue, at 3 h after injection) and tumor imaging contrast, whereas coinjection with 500 μg of Ac-Cys-Z(EGFR:1907) successfully blocked the tumor uptake significantly (8.1 vs. 1.0 percentage of the injected radioactive dose per gram of tissue, at 3 h after injection, 88% inhibition, P < 0.05). Moderate correlation was found between the tumor tracer uptake at 3 h after injection quantified by PET and EGFR expression levels measured by Western blot assay (P = 0.007, R = 0.59).Conclusion(18)F-FBEM-Cys-Z(EGFR:1907) is a novel protein scaffold-based PET probe for imaging EGFR overexpression of tumors, and its ability to differentiate tumors with high and low EGFR expression in vivo holds promise for future clinical translation.

Project description:PurposeThe purpose of this study was to explore the application of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) image radiomics in the identification of spine multiple myeloma (MM) and bone metastasis (BM), and whether this method could improve the classification diagnosis performance compared with traditional methods.MethodsThis retrospective study collected a total of 184 lesions from 131 patients between January 2017 and January 2021. All images were visually evaluated independently by two physicians with 20 years of experience through the double-blind method, while the maximum standardized uptake value (SUVmax) of each lesion was recorded. A total of 279 radiomics features were extracted from the region of interest (ROI) of CT and PET images of each lesion separately by manual method. After the reliability test, the least absolute shrinkage and selection operator (LASSO) regression and 10-fold cross-validation were used to perform dimensionality reduction and screening of features. Two classification models of CT and PET were derived from CT images and PET images, respectively and constructed using the multivariate logistic regression algorithm. In addition, the ComModel was constructed by combining the PET model and the conventional parameter SUVmax. The performance of the three classification diagnostic models, as well as the human experts and SUVmax, were evaluated and compared, respectively.ResultsA total of 8 and 10 features were selected from CT and PET images for the construction of radiomics models, respectively. Satisfactory performance of the three radiomics models was achieved in both the training and the validation groups (Training: AUC: CT: 0.909, PET: 0.949, ComModel: 0.973; Validation: AUC: CT: 0.897, PET: 0.929, ComModel: 0.948). Moreover, the PET model and ComModel showed significant improvement in diagnostic performance between the two groups compared to the human expert (Training: P = 0.01 and P = 0.001; Validation: P = 0.018 and P = 0.033), and no statistical difference was observed between the CT model and human experts (P = 0.187 and P = 0.229, respectively).ConclusionThe radiomics model constructed based on 18F-FDG PET/CT images achieved satisfactory diagnostic performance for the classification of MM and bone metastases. In addition, the radiomics model showed significant improvement in diagnostic performance compared to human experts and PET conventional parameter SUVmax.

Project description:BackgroundDeriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regard to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM).Methods2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of 37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in different commercially available software packages. PET standard uptake values (SUV) were corrected for: (1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter and (2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak and maximum SUV were investigated using Student's t test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis. These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SURMEAN, SURPEAK and SURMAX, respectively.ResultsFifteen patients harbored KRAS missense mutations (KRAS+), while another 3 harbored KRAS gene amplification. For 31 lesions, the mutational status was derived from the PET/CT-guided biopsy. The Student's t test p values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SURMAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve = 0.77 and 0.75 for the two different segmentations, respectively, with a mean specificity of 0.69 and sensitivity of 0.85.ConclusionThe correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.

Dataset Information

PET of HER2-positive pulmonary metastases with 18F-ZHER2:342 affibody in a murine model of breast cancer: comparison with 18F-FDG.

Publications

PET of HER2-positive pulmonary metastases with 18F-ZHER2:342 affibody in a murine model of breast cancer: comparison with 18F-FDG.

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