scholarly journals Early Detection of Checkpoint Inhibitor-Associated Myocarditis Using 68Ga-FAPI PET/CT

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniel Finke ◽  
Markus B. Heckmann ◽  
Esther Herpel ◽  
Hugo A. Katus ◽  
Uwe Haberkorn ◽  
...  

Objective: Checkpoint inhibitors (ICIs) have gained importance in recent years regarding the treatment of a variety of oncologic diseases. The possibilities of diagnosing cardiac adverse autoimmune effects of ICIs are still limited. We aimed to implement FAPI PET/CT imaging in detecting ICI-associated myocarditis.Methods: In a retrospective study, FAPI PET/CT scans of 26 patients who received ICIs from 01/2017 to 10/2019 were analyzed. We compared tracer enrichment in the heart of patients without any signs of a cardiac disease (n = 23) to three patients with suspected ICI-associated myocarditis. To exclude any significant coronary heart disease, cardiac catherization was performed. All three patients' myocardial biopsies were examined for inflammatory cells.Results: Three patients showed clinical manifestations of an ICI syndrome including myocarditis with elevated levels of hsTnT (175 pg/ml, 1,771 pg/ml, 157 pg/ml). Further cardiological assessments revealed ECG abnormalities, lymphocyte infiltration of the myocardium in the biopsies or wall motion abnormalities in echocardiography. These patients' FAPI PET/CTs showed cardiac enrichment of the marker which was less distinct or absent in patients receiving ICIs without any signs of immunological adverse effects or cardiac impairment (n = 23) [Median SUV myocarditis patients: 1.79 (IQR: 1.65, 1.85), median SUV non-myocarditis patients: 1.15 (IQR: 0.955, 1.52)].Conclusions: Apart from the successful implementation of ICIs in oncological treatments, ICI-associated myocarditis is still a challenging adverse effect. FAPI PET/CT may be used in order to identify affected patients at an early stage. Moreover, when integrated into cancer stage diagnostics, it contributes to cardiac risk stratification besides biomarker, ECG and echocardiography.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Daniel Finke ◽  
Markus B Heckmann ◽  
Esther Herpel ◽  
Hugo A Katus ◽  
Uwe Haberkorn ◽  
...  

Introduction: Checkpoint inhibitors (ICIs) have gained importance in recent years regarding the treatment of a variety of oncologic diseases. The possibilities of diagnosing cardiac adverse autoimmune effects of ICIs are still limited. We aimed to implement FAPI PET/CT imaging in detecting ICI-induced myocarditis. Methods: In a retrospective study, FAPI PET/CT scans of 26 patients who received ICIs from 01/2017 to 10/2019 were analyzed. We compared tracer enrichment in the heart of patients without any signs of a cardiac disease (n=23) to three patients with suspected ICI-induced myocarditis. To exclude any significant coronary heart disease, cardiac catherization was performed. Myocardial biopsies were examined, especially in regard to the infiltration of immune cells. Results: Three patients showed clinical manifestations of an ICI syndrome including myocarditis with elevated levels of hsTnT (175 pg/ml, 1771 pg/ml, 157 pg/ml). Further cardiological assessments revealed ECG abnormalities, lymphocyte infiltration of the myocardium in the biopsies or wall motion abnormalities in echocardiography. These patients’ FAPI PET/CTs showed a locally defined cardiac enrichment of the marker which was absent in patients receiving ICIs without any signs of immunological adverse effects and cardiac impairment (n=23) (Median SUV myocarditis patients: 1.79 (IQR: 1.65, 1.85), median SUV non-myocarditis patients: 1.15 (IQR: 0.955, 1.52)). Conclusions: Myocardial biopsy, the current gold standard of the diagnosis of ICI-induced myocarditis, is susceptible to sampling errors and results arrive within a few days. We provide first evidence that FAPI PET/CT is able to diagnose ICI-induced myocarditis and can demonstrate locally enhanced manifestation of ICI-induced myocarditis on time.


2020 ◽  
Author(s):  
Zhehao Lyu ◽  
Lili Liu ◽  
Huimin Li ◽  
Haibo Wang ◽  
Qi Liu ◽  
...  

Abstract Background: Collective duct carcinoma (CDC) is a highly malignant kidney tumor which is rare in clinical. We report our 12-year experience of Collecting (Bellini) duct carcinoma (CDC) and retrospectively analyzed patients and tumour characteristics, clinical manifestations, different imaging characteristics including CT, MRI and PET/CT. Methods: From January 2007 to December 2019, we retrospectively examined all renal tumors and identifed 13 cases of CDC from 3 medical centers in the northern China. All 13 patients underwent CT scan, 8 of whom underwent dynamic enhanced CT scan, 2 underwent PET/CT scan and 1 underwent MRCP examination. The lesions were divided into nephritis type and mass type according to the morphology of the tumors.Results: The study group included 10 men and 3 women, with an average age of 64.23±10.74 years old. Of these 13 patients, the main clinical manifestations include gross hematuria, flank pain or waist discomfort. The mean tumour size was 8.48 ± 2.48 cm. In this group of cases, 6 (46.2%) cases are cortical-medullary involved type, 7 (53.8%) cases are cortex-medullary-pelvis involved type. 11 (84.6%) cases were nephritis type and 2 (15.4%) cases were mass type. The lesions appeared solid or complex solid and cystic on CT and MRI. The parenchymal part of 13 CDC tumors showed isodensity or slightly higher density on unenhanced CT scan. the parenchymal part of 13 CDC tumors showed isodensity or slightly higher density on unenhanced CT scan. Two patients with PET/CT showed increased radioactivity intake. Evidence of intra-abdominal metastatic disease was present on CT in 9 ( 69.2% ) cases. The incidence of metastasis reached 69%.Conclusions: The Collecting (Bellini) duct carcinoma has its certain imaging characteristics which were different from the other renal cell carcinoma. A renal tumor should be considered as CDC when it locates in the junction zone of the renal cortex and medulla, with unclear border, slight enhancement and metastases in early stage. PET/CT can greatly enrich the key information of diagnosis, surgery and treatment options, which provide significant help to the clinic.


2014 ◽  
Vol 120 (3) ◽  
pp. 683-693 ◽  
Author(s):  
Guido Musch ◽  
Tilo Winkler ◽  
R. Scott Harris ◽  
Marcos F. Vidal Melo ◽  
Tyler J. Wellman ◽  
...  

Abstract Background: Acute lung injury occurs in a third of patients with smoke inhalation injury. Its clinical manifestations usually do not appear until 48–72 h after inhalation. Identifying inflammatory changes that occur in pulmonary parenchyma earlier than that could provide insight into the pathogenesis of smoke-induced acute lung injury. Furthermore, noninvasive measurement of such changes might lead to earlier diagnosis and treatment. Because glucose is the main source of energy for pulmonary inflammatory cells, the authors hypothesized that its pulmonary metabolism is increased shortly after smoke inhalation, when classic manifestations of acute lung injury are not yet expected. Methods: In five sheep, the authors induced unilateral injury with 48 breaths of cotton smoke while the contralateral lung served as control. The authors used positron emission tomography with: (1) [18F]fluorodeoxyglucose to measure metabolic activity of pulmonary inflammatory cells; and (2) [13N]nitrogen in saline to measure shunt and ventilation–perfusion distributions separately in the smoke-exposed and control lungs. Results: The pulmonary [18F]fluorodeoxyglucose uptake rate was increased at 4 h after smoke inhalation (mean ± SD: 0.0031 ± 0.0013 vs. 0.0026 ± 0.0010 min−1; P < 0.05) mainly as a result of increased glucose phosphorylation. At this stage, there was no worsening in lung aeration or shunt. However, there was a shift of perfusion toward units with lower ventilation-to-perfusion ratio (mean ratio ± SD: 0.82 ± 0.10 vs. 1.12 ± 0.02; P < 0.05) and increased heterogeneity of the ventilation–perfusion distribution (mean ± SD: 0.21 ± 0.07 vs. 0.13 ± 0.01; P < 0 .05). Conclusion: Using noninvasive imaging, the authors demonstrated that increased pulmonary [18F]fluorodeoxyglucose uptake and ventilation–perfusion mismatch occur early after smoke inhalation.


2020 ◽  
Author(s):  
Zhehao Lyu ◽  
Lili Liu ◽  
Huimin Li ◽  
Haibo Wang ◽  
Qi Liu ◽  
...  

Abstract Background: Collective duct carcinoma (CDC) is a highly malignant kidney tumor which is rare in clinical. We report our 12-year experience of Collecting (Bellini) duct carcinoma (CDC) and retrospectively analyzed patients and tumour characteristics, clinical manifestations, different imaging characteristics including CT, MRI and PET/CT. Methods: From January 2007 to December 2019, we retrospectively examined all renal tumors and identifed 13 cases of CDC and tried to improve the understanding of the imaging features of the disease.Results: The study group included 10 men and 3 women, with an average age of 64.23±10.74 years old. Of these 13 patients, the main clinical manifestations include gross hematuria, flank pain or waist discomfort. The mean tumour size was 8.48 ± 2.48 cm. In this group of cases, 6 cases are cortical-medullary involved type, 7 cases are cortex-medullary-pelvis involved type. 11 cases were nephritis type and 2 cases were mass type. The lesions appeared solid or complex solid and cystic on CT and MRI. The parenchymal part of 13 CDC tumors showed isodensity or slightly higher density on unenhanced CT scan. Two patients with PET/CT showed increased radioactivity intake. Evidence of intra-abdominal metastatic disease was present on CT in 9 of 13 ( 69.23% ) cases. The incidence of metastasis reached 69%.Conclusions: The Collecting (Bellini) duct carcinoma has its certain imaging characteristics which were different from the other renal cell carcinoma. A renal tumor should be considered as CDC when it locates in the junction zone of the renal cortex and medulla, with unclear border, slight enhancement and metastases in early stage. PET/CT can greatly enrich the key information of diagnosis, surgery and treatment options, which provide significant help to the clinic.


2020 ◽  
Vol 13 (1) ◽  
pp. 24-31 ◽  
Author(s):  
Angelo Castello ◽  
Egesta Lopci

Background: Immune checkpoint inhibitors (ICI) have achieved astonishing results and improved overall survival (OS) in several types of malignancies, including advanced melanoma. However, due to a peculiar type of anti-cancer activity provided by these drugs, the response patterns during ICI treatment are completely different from that with “old” chemotherapeutic agents. Objective: To provide an overview of the available literature and potentials of 18F-FDG PET/CT in advanced melanoma during the course of therapy with ICI in the context of treatment response evaluation. Methods: Morphologic criteria, expressed by Response Evaluation Criteria in Solid Tumors (RECIST), immune-related response criteria (irRC), irRECIST, and, more recently, immune-RECIST (iRECIST), along with response criteria based on the metabolic parameters with 18F-Fluorodeoxyglucose (18FFDG), have been explored. Results: To overcome the limits of traditional response criteria, new metabolic response criteria have been introduced on time and are being continuously updated, such as the PET/CT Criteria for the early prediction of Response to Immune checkpoint inhibitor Therapy (PECRIT), the PET Response Evaluation Criteria for Immunotherapy (PERCIMT), and “immunotherapy-modified” PET Response Criteria in Solid Tumors (imPERCIST). The introduction of new PET radiotracers, based on monoclonal antibodies combined with radioactive elements (“immune-PET”), are of great interest. Conclusion: Although the role of 18F-FDG PET/CT in malignant melanoma has been widely validated for detecting distant metastases and recurrences, evidences in course of ICI are still scarce and larger multicenter clinical trials are needed.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhehao Lyu ◽  
Lili Liu ◽  
Huimin Li ◽  
Haibo Wang ◽  
Qi Liu ◽  
...  

Abstract Background Collecting (Bellini) duct carcinoma (CDC) is a highly malignant and rare kidney tumor. We report our 12-year experience with CDC and the results of a retrospective analysis of patients and tumor characteristics, clinical manifestations, and imaging features by computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT. Methods Retrospective examination of tumors between January 2007 and December 2019 identified 13 cases of CDC from three medical centers in northern China. All 13 patients underwent CT scan, among which eight underwent dynamic enhanced CT scan, two underwent PET/CT scan, and one underwent magnetic resonance cholangiopancreatography (MRCP) examination. The lesions were divided into nephritis type and mass type according to the morphology of the tumors. Results The study group included ten men and three women with an average age of 64.23 ± 10.74 years. The clinical manifestations were gross hematuria, flank pain, and waist discomfort. The mean tumor size was 8.48 ± 2.48 cm. Of the 13 cases, six (46.2%) were cortical-medullary involved type and seven (53.8%) were cortex–medullary–pelvis involved type. Eleven (84.6%) cases were nephritis type and two (15.4%) were mass type. The lesions appeared solid or complex solid and cystic on CT and MRI. The parenchymal area of the tumors showed isodensity or slightly higher density on unenhanced CT scan in the 13 cases. PET/CT in two cases showed increased radioactivity intake. Evidence of intra-abdominal metastatic disease was present on CT in nine (69.2%) cases. Conclusions The imaging characteristics of CDC differ from those of other renal cell carcinomas. In renal tumors located in the junction zone of the renal cortex and medulla that show unclear borders, slight enhancement, and metastases in the early stage, a diagnosis of CDC needs to be considered. PET/CT provides crucial information for the diagnosis of CDC, as well as for designing treatment strategies including surgery.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kang Sun ◽  
Yi-yuan Li ◽  
Jin Jin

AbstractThe response of immune cells in cardiac injury is divided into three continuous phases: inflammation, proliferation and maturation. The kinetics of the inflammatory and proliferation phases directly influence the tissue repair. In cardiac homeostasis, cardiac tissue resident macrophages (cTMs) phagocytose bacteria and apoptotic cells. Meanwhile, NK cells prevent the maturation and transport of inflammatory cells. After cardiac injury, cTMs phagocytose the dead cardiomyocytes (CMs), regulate the proliferation and angiogenesis of cardiac progenitor cells. NK cells prevent the cardiac fibrosis, and promote vascularization and angiogenesis. Type 1 macrophages trigger the cardioprotective responses and promote tissue fibrosis in the early stage. Reversely, type 2 macrophages promote cardiac remodeling and angiogenesis in the late stage. Circulating macrophages and neutrophils firstly lead to chronic inflammation by secreting proinflammatory cytokines, and then release anti-inflammatory cytokines and growth factors, which regulate cardiac remodeling. In this process, dendritic cells (DCs) mediate the regulation of monocyte and macrophage recruitment. Recruited eosinophils and Mast cells (MCs) release some mediators which contribute to coronary vasoconstriction, leukocyte recruitment, formation of new blood vessels, scar formation. In adaptive immunity, effector T cells, especially Th17 cells, lead to the pathogenesis of cardiac fibrosis, including the distal fibrosis and scar formation. CMs protectors, Treg cells, inhibit reduce the inflammatory response, then directly trigger the regeneration of local progenitor cell via IL-10. B cells reduce myocardial injury by preserving cardiac function during the resolution of inflammation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hye Seong ◽  
Yong Hyu Jeong ◽  
Woon Ji Lee ◽  
Jun Hyoung Kim ◽  
Jung Ho Kim ◽  
...  

AbstractKikuchi-Fujimoto disease (KFD) is usually self-limiting, but prolonged systemic symptoms often result in frequent hospital visits, long admission durations, or missed workdays. We investigated the role of fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing KFD severity. We reviewed the records of 31 adult patients with pathologically confirmed KFD who underwent 18F-FDG PET/CT between November 2007 and April 2018 at a tertiary-care referral hospital. Disease severity was assessed using criteria based on clinical manifestations of advanced KFD. Systemic activated lymph nodes and severity of splenic activation were determined using semi-quantitative and volumetric PET/CT parameters. The median of the mean splenic standardized uptake value (SUVmean) was higher in patients with severe KFD than those with mild KFD (2.38 ± 1.18 vs. 1.79 ± 0.99, p = 0.058). Patients with severe KFD had more systemically activated volume and glycolytic activity than those with mild KFD (total lesion glycolysis: 473.5 ± 504.4 vs. 201.6 ± 363.5, p = 0.024). Multivariate logistic regression showed that myalgia (odds ratio [OR] 0.035; 95% confidence interval [CI] 0.001–0.792; p = 0.035), total lymph node SUVmax (cutoff 9.27; OR 24.734; 95% CI 1.323–462.407; p = 0.032), and spleen SUVmean (cutoff 1.79; OR 37.770; 95% CI 1.769–806.583; p = 0.020) were significantly associated with severe KFD. 18F-FDG PET/CT could be useful in assessing KFD severity.


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