Fibroblast Activation Protein specific PET/CT imaging in fibrotic interstitial lung diseases and lung cancer: a translational exploratory study.

Abstract Purpose Radionuclide-labeled fibroblast-activation-protein inhibitor 04 (FAPI-04) as a positron emission tomography (PET) imaging tracer can reveal the localized expression of fibroblast activation protein (FAP), a cell-surface serine protease that is highly upregulated in more than 90% of epithelial carcinomas. In this study, we quantified the 18F-NOTA-FAPI-04 uptake on PET/computed tomography (CT) imaging in different pathological types of lung cancer and metastatic tumors. Methods We prospectively enrolled 61 patients with histopathologically proven primary lung cancer with metastases.PET/CT scanning was performed before any antitumor therapy and 1hour after injection of 235.10 ± 3.89 MBq of 18F-NOTA-FAPI-04. Maximum standard uptake values (SUVmax) were calculated for comparison among primary and metastatic lesions. Results Sixty-one patients with adenocarcinoma (ADC, n = 30), squamous cell carcinoma (SCC, n = 17), and small cell lung cancer (SCLC, n = 14) were enrolled in this study, and 61 primary tumors and 199 metastases were evaluated. No difference in18F-NOTA-FAPI-04 uptake was observed among primary ADC, SCC, and SCLC tumors (P = 0.198).Additionally, no difference in uptake was found between primary and metastatic lesions of lung cancer with the same pathological type (P > 0.05).However, uptake did differ among metastases of differing pathological type (P < 0.001). The SUVmax of metastatic lymph nodes was highest for SCC, followed by ADC and then SCLC (P < 0.001).The SUVmax of bone metastases also was highest for SCC, followed by ADC and SCLC (P < 0.05), but no difference was observed between ADC and SCLC. The SUVmax of metastases in other organs was higher in SCC cases than in ADC cases, but did not differ between SCC and SCLC or ADC and SCLC. Bone metastases exhibited higher uptake than those of lymph nodes and other organs in SCC and ADC (P < 0.05), but not in SCLC. Conclusion 18F-NOTA-FAPI-04 PET/CT imaging revealed differences in FAP expression in metastases of lung cancer, with the highest expression specifically in bone metastases, and thus, may be valuable for distinguishing different pathological types of lung cancer.

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Clinical Translational Evaluation of Al18F-NOTA-FAPI for Fibroblast Activation Protein Targeted Tumour Imaging

10.21203/rs.3.rs-231262/v1 ◽

2021 ◽

Author(s):

Shuailiang Wang ◽

Xin Zhou ◽

Xiaoxia Xu ◽

Jin Ding ◽

Song Liu ◽

...

Keyword(s):

Cancer Patients ◽

Fibroblast Activation Protein ◽

Ct Imaging ◽

Whole Body ◽

Tumour Imaging ◽

Tumour Detection ◽

Fibroblast Activation ◽

Tumour Bearing ◽

Pet Ct ◽

18F Fdg

Abstract PurposeIn this study, a novel Al18F-NOTA-FAPI probe was developed for fibroblast activation protein (FAP) targeted tumour imaging, which was available to achieve curie level radioactivity by automatic synthesizer. The tumour detection efficacy of Al18F-NOTA-FAPI was further validated both in preclinical and clinical translational studies. MethodsThe radiolabeling procedure of Al18F-NOTA-FAPI was optimized. Cell uptake and competitive binding assay were completed with U87MG and A549 cell lines, to evaluate the affinity and specificity of Al18F-NOTA-FAPI probe. The biodistribution, pharmacokinetics, radiation dosimetry and tumour imaging efficacy of Al18F-NOTA-FAPI probe were researched with healthy Kunming (KM) and/or U87MG model mice. After the approval of ethical committee, Al18F-NOTA-FAPI probe was translated into clinical for the PET/CT imaging of first 10 cancer patients. ResultsThe radiolabeling yield of Al18F-NOTA-FAPI was 33.8 ± 3.2% through manually operation (n = 10), with the radiochemical purity over than 99% and the specific activity of 9.3-55.5 MBq/nmol. Whole body effective dose of Al18F-NOTA-FAPI was estimated to be 1.24E-02 mSv/MBq, lower than several other FAPI probes ( 68Ga-FAPI-04, 68Ga-FAPI-46 and 68Ga-FAPI-74). In U87MG tumour bearing mice, Al18F-NOTA-FAPI showed good tumor detection efficacy from the results of micro PET/CT imaging and biodistribution studies. In organ biodistribution study of human patients, Al18F-NOTA-FAPI showed lower SUVmean than 2-[18F]FDG in most organs, especially in liver (1.1 ± 0.2 vs. 2.0 ± 0.9), brain (0.1 ± 0.0 vs. 5.9 ± 1.3), and bone marrow (0.9 ± 0.1 vs. 1.7 ± 0.4). Meanwhile, Al18F-NOTA-FAPI do not show extensive bone uptakes, and was able to find out more tumour lesions than 2-[18F]FDG in the PET/CT imaging of several patients. ConclusionAl18F-NOTA-FAPI probe was successfully fabricated and applied in fibroblast activation protein targeted tumour PET/CT imaging, which showed excellent imaging quality and tumour detection efficacy in U87MG tumour bearing mice as well as in human cancer patients.

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PET/CT Imaging of Small Cell Lung Cancer Using 89Zr-DFO-SC16.56

Case Medical Research ◽

10.31525/ct1-nct04199741 ◽

2019 ◽

Author(s):

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Ct Imaging ◽

Small Cell ◽

Small Cell Lung ◽

Pet Ct

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Automating Lung Cancer Identification in PET/CT Imaging

2018 IEEE 4th International Forum on Research and Technology for Society and Industry (RTSI) ◽

10.1109/rtsi.2018.8548388 ◽

2018 ◽

Author(s):

E. D'Arnese ◽

E. Del Sozzo ◽

A. Chiti ◽

T. Berger-Wolf ◽

M. D. Santambrogio

Keyword(s):

Lung Cancer ◽

Ct Imaging ◽

Pet Ct

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Volumetric Imaging of Lung Tissue at Micrometer Resolution: Clinical Applications of Micro-CT for the Diagnosis of Pulmonary Diseases

Diagnostics ◽

10.3390/diagnostics11112075 ◽

2021 ◽

Vol 11 (11) ◽

pp. 2075

Author(s):

Andreana Bompoti ◽

Andreas S. Papazoglou ◽

Dimitrios V. Moysidis ◽

Nikolaos Otountzidis ◽

Efstratios Karagiannidis ◽

...

Keyword(s):

Lung Cancer ◽

Lung Tissue ◽

Lung Diseases ◽

Human Lung ◽

Imaging Modality ◽

Clinical Applications ◽

Ct Imaging ◽

Micro Ct ◽

Volumetric Imaging ◽

Scoping Reviews

Micro-computed tomography (micro-CT) is a promising novel medical imaging modality that allows for non-destructive volumetric imaging of surgical tissue specimens at high spatial resolution. The aim of this study is to provide a comprehensive assessment of the clinical applications of micro-CT for the tissue-based diagnosis of lung diseases. This scoping review was conducted in accordance with the PRISMA Extension for Scoping Reviews, aiming to include every clinical study reporting on micro-CT imaging of human lung tissues. A literature search yielded 570 candidate articles, out of which 37 were finally included in the review. Of the selected studies, 9 studies explored via micro-CT imaging the morphology and anatomy of normal human lung tissue; 21 studies investigated microanatomic pulmonary alterations due to obstructive or restrictive lung diseases, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and cystic fibrosis; and 7 studies examined the utility of micro-CT imaging in assessing lung cancer lesions (n = 4) or in transplantation-related pulmonary alterations (n = 3). The selected studies reported that micro-CT could successfully detect several lung diseases providing three-dimensional images of greater detail and resolution than routine optical slide microscopy, and could additionally provide valuable volumetric insight in both restrictive and obstructive lung diseases. In conclusion, micro-CT-based volumetric measurements and qualitative evaluations of pulmonary tissue structures can be utilized for the clinical management of a variety of lung diseases. With micro-CT devices becoming more accessible, the technology has the potential to establish itself as a core diagnostic imaging modality in pathology and to enable integrated histopathologic and radiologic assessment of lung cancer and other lung diseases.

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Dynamic PET/CT Imaging of 68Ga-FAPI-04 in Chinese Subjects

Frontiers in Oncology ◽

10.3389/fonc.2021.651005 ◽

2021 ◽

Vol 11 ◽

Author(s):

Shuailiang Wang ◽

Xin Zhou ◽

Xiaoxia Xu ◽

Jin Ding ◽

Teli Liu ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Body Mass ◽

Fdg Pet ◽

Radiation Dosimetry ◽

Ct Imaging ◽

Lung Cancer Patients ◽

Pet Ct ◽

Fdg Pet Ct ◽

Chinese Subjects

This study aims to further explore dynamic 68Ga-FAPI-04 PET/CT imaging of healthy Chinese subjects and lung cancer patients. Moreover, the variability of 68Ga-FAPI-04 uptake in normal organs was measured to provide a basis for analyzing its biological distribution, interpreting auxiliary images, determining the reliability of image quantification, and monitoring treatment. Six patients (3 subjects without tumors and 3 lung cancer patients) separately underwent 68Ga-FAPI-04 and 2-[18F]FDG PET/CT imaging within 1 week. The biodistribution and internal radiation dosimetry were reported and compared with data previously obtained from Caucasian patients. Moreover, the mean SUV (standardized uptake value) was normalized to body mass or to lean body mass (SUL), and the coefficients of variation (CVs) were calculated and compared for each volume of interest. The average whole-body effective dose was calculated to be 1.27E-02 mSv/MBq, which was comparable with previously reported results of 68Ga-FAPI-04 probes. Furthermore, the SUVmean was slightly higher than the SULmean in most organs; however, the CV of the SULmean for most organs was higher than that of the SUVmean at later time points. In the liver, the CV of the SUVmean was lower (12.7%) than that of the SULmean and was similar to the CV for corresponding 2-[18F]FDG PET/CT value (11.8%). In addition, 68Ga-FAPI-04 PET/CT showed good efficacy for diagnosing lung cancer patients in this study. A comparison of the radiation dosimetry obtained before from a Caucasian population demonstrated no clinically significant differences between these two populations after 68Ga-FAPI-04 injection. The variability in most organs was slightly lower for SUVmean than for SULmean, suggesting that SUVmean may be the preferable parameter for quantifying images obtained with 68Ga-FAPI-04. In addition, 68Ga-FAPI-04 PET/CT imaging is expected to be a promising tool for diagnosing lung cancer.

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PET/CT imaging in lung cancer: indications and findings

Jornal Brasileiro de Pneumologia ◽

10.1590/s1806-37132015000004479 ◽

2015 ◽

Vol 41 (3) ◽

pp. 264-274 ◽

Cited By ~ 26

Author(s):

Bruno Hochhegger ◽

Giordano Rafael Tronco Alves ◽

Klaus Loureiro Irion ◽

Carlos Cezar Fritscher ◽

Leandro Genehr Fritscher ◽

...

Keyword(s):

Lung Cancer ◽

Pulmonary Nodules ◽

Cancer Staging ◽

Ct Imaging ◽

Inappropriate Treatment ◽

Pet Ct ◽

Disease Staging ◽

Anatomical Information ◽

Work Up

The use of PET/CT imaging in the work-up and management of patients with lung cancer has greatly increased in recent decades. The ability to combine functional and anatomical information has equipped PET/CT to look into various aspects of lung cancer, allowing more precise disease staging and providing useful data during the characterization of indeterminate pulmonary nodules. In addition, the accuracy of PET/CT has been shown to be greater than is that of conventional modalities in some scenarios, making PET/CT a valuable noninvasive method for the investigation of lung cancer. However, the interpretation of PET/CT findings presents numerous pitfalls and potential confounders. Therefore, it is imperative for pulmonologists and radiologists to familiarize themselves with the most relevant indications for and limitations of PET/CT, seeking to protect their patients from unnecessary radiation exposure and inappropriate treatment. This review article aimed to summarize the basic principles, indications, cancer staging considerations, and future applications related to the use of PET/CT in lung cancer.

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Idiopathic Pulmonary Fibrosis

Chest Imaging ◽

10.1093/med/9780199858064.003.0078 ◽

2019 ◽

pp. 453-457

Author(s):

Cylen Javidan-Nejad

Keyword(s):

Lung Cancer ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Pulmonary Edema ◽

Interstitial Pneumonia ◽

Lung Diseases ◽

Usual Interstitial Pneumonia ◽

Primary Lung Cancer ◽

Interstitial Lung Diseases ◽

Pathologic Diagnosis

Idiopathic pulmonary fibrosis (IPF) represents one of the most common chronic interstitial lung diseases. Usual interstitial pneumonia (UIP) is the pathologic diagnosis of IPF and can be diagnosed when honeycombing is present with a basilar and peripheral predominance and findings not typical of UIP are absent. In the current era, when a diagnosis of UIP is made with confidence on HRCT, biopsy can be avoided. Yet, one must be familiar with mimics of UIP/IPF (most notably pulmonary edema superimposed on emphysema) to avoid confusion misdiagnosis. Radiologists must also be familiar with potential complications of UIP including progression, infection, accelerated fibrosis (which can be lethal) and primary lung cancer (which has an increased incidence in UIP).

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