68Ga-DOTATOC PET/CT to detect immune checkpoint inhibitor-related myocarditis.

Details

Ressource 1Download: 34686542_BIB_6D88B7F593BA.pdf (4431.80 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_6D88B7F593BA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
68Ga-DOTATOC PET/CT to detect immune checkpoint inhibitor-related myocarditis.
Journal
Journal for immunotherapy of cancer
Author(s)
Boughdad S., Latifyan S., Fenwick C., Bouchaab H., Suffiotti M., Moslehi J.J., Salem J.E., Schaefer N., Nicod-Lalonde M., Costes J., Perreau M., Michielin O., Peters S., Prior J.O., Obeid M.
ISSN
2051-1426 (Electronic)
ISSN-L
2051-1426
Publication state
Published
Issued date
10/2021
Peer-reviewed
Oui
Volume
9
Number
10
Pages
e003594
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Immune checkpoint inhibitor (ICI)-related myocarditis is a rare but potentially fatal adverse event that can occur following ICI exposure. Early diagnosis and treatment are key to improve patient outcomes. Somatostatin receptor-based positron emission tomography-CT (PET/CT) showed promising results for the assessment of myocardial inflammation, yet information regarding its value for the diagnosis of ICI-related myocarditis, especially at the early stage, is limited. Thus, we investigated the value of <sup>68</sup> Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide ( <sup>68</sup> Ga-DOTATOC) PET/CT for the early detection and diagnosis of ICI-related myocarditis.
Consecutive patients with clinically suspected ICI-related myocarditis from July 2018 to February 2021 were retrospectively evaluated in this single-center study. All patients underwent imaging for the detection of ICI-related myocarditis using either cardiac magnetic resonance (CMR) imaging or <sup>68</sup> Ga-DOTATOC PET/CT. PET/CT images were acquired 90 min after the injection of 2 MBq/kg <sup>68</sup> Ga-DOTATOC with pathological myocardial uptake in the left ventricle (LV) suggestive of myocarditis defined using a myocardium-to-background ratio of peak standard uptake value to mean intracavitary LV standard uptake (MBR <sub>peak</sub> ) value above 1.6. Patients had a full cardiological work-up including ECG, echocardiography, serum cardiac troponin I (cTnI), cardiac troponin T and creatine kinase (CK), CK-MB. Endomyocardial biopsy and inflammatory cytokine markers were also analyzed. The detection rate of ICI-related myocarditis using <sup>68</sup> Ga-DOTATOC PET/CT and CMR was assessed.
A total of 11 patients had clinically suspected ICI-related myocarditis; 9 underwent <sup>68</sup> Ga -DOTATOC PET/CT. All nine (100%) patients with <sup>68</sup> Ga-DOTATOC PET/CT presented with pathological myocardial uptake in the LV that was suggestive of myocarditis (MBR <sub>peak</sub> of 3.2±0.8, range 2.2-4.4). Eight patients had CMR imaging and 3/8 (38%) patients had lesions evocative of myocarditis. All PET-positive patients were previously treated with a high dose of steroids and intravenous immunoglobulin prior to PET/CT had elevated serum cTnI except for one patient for whom PET/CT was delayed several days. Interestingly, in 5/6 (83%) patients who presented with concomitant myositis, pathological uptake was seen on whole-body <sup>68</sup> Ga-DOTATOC PET/CT images in the skeletal muscles, suggesting an additional advantage of this method to assess the full extent of the disease. In contrast, four patients with CMR imaging had negative findings despite having elevated serum cTnI levels (range 20.5-5896.1 ng/mL), thus defining possible myocarditis. Newly identified immune correlates could provide specific biomarkers for the diagnosis of ICI-related myocarditis. Most tested patients (six of seven patients) had serum increases in the inflammatory cytokine interleukin (IL)-6 and in the chemokines CXCL9, CXCL10, and CXCL13, and the mass cytometry phenotypes of immune cell populations in the blood also showed correlations with myocardial inflammation. Four of five patients with myocarditis exhibited a Th1/Th2 imbalance favoring a pronounced inflammatory Th1, Th1/Th17, and Th17 CD4 memory T-cell response. The high proportion of non-classical monocytes and significantly reduced levels of CD31 in four to five patients was also consistent with an inflammatory disease.
The use of <sup>68</sup> Ga-DOTATOC PET/CT along with immune correlates is a highly sensitive method to detect ICI-related myocarditis especially in the early stage of myocardial inflammation, as patients with elevated cTnI may present normal CMR imaging results. <sup>68</sup> Ga-DOTATOC PET/CT is also useful for detecting concomitant myositis. These results need to be confirmed in a larger population of patients and validated against a histological gold standard if available.
Keywords
Aged, Female, Gallium Radioisotopes/therapeutic use, Humans, Immune Checkpoint Inhibitors/adverse effects, Male, Myocarditis/chemically induced, Myocarditis/diagnostic imaging, Positron Emission Tomography Computed Tomography/methods, immunotherapy
Pubmed
Web of science
Open Access
Yes
Create date
05/11/2021 18:33
Last modification date
21/11/2022 8:22
Usage data