Molecular Imaging Using Cardiac PET/CT: Opportunities to Harmonize Diagnosis and Therapy

Thackeray, James T.

doi:10.1007/s11886-021-01526-y

Cited by 4 publications

(3 citation statements)

References 90 publications

(118 reference statements)

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“…Our rationale for targeting TSPO was the prominent role that oxidative stress and inflammation play in DOX-induced cardiotoxicity. 37 TSPO is expressed not only in cardiomyocytes 97 but also in activated immune cells, especially macrophages. [98][99][100] Resident and circulating macrophages are implicated in the response to DOX-induced cardiotoxicity.…”

Section: Discussionmentioning

confidence: 99%

PET imaging of fibroblast activation protein alpha (FAP) detects incipient cardiotoxicity due to anthracycline chemotherapy

Lee,

Manzo,

Rubinelli

et al. 2023

Preprint

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Background: Anthracycline chemotherapy is associated with a risk of cardiotoxicity leading to heart disease, particularly in pediatric cancer patients. Gold standard methods of detecting cardiotoxicity are insufficiently sensitive to early damage and specific pathophysiologies driving disease. Positron emission tomography (PET) couples anatomical resolution with biochemical mechanistic selectivity and potentially addresses the current diagnostic limitations in cardio-oncology. We aimed to validate PET imaging biomarkers targeting fibroblast activation protein alpha (FAP), Translocator protein (TSPO), and norepinephrine receptor (NET) for detection of incipient anthracycline-induced cardiotoxicity. Methods: Cardiotoxicity was established in male C57BL/6J mice by a cumulative dose of 24 mg/kg doxorubicin (DOX) over 2 weeks. DOX mice and their age-matched controls were imaged with echocardiography and PET, using [68Ga]Ga-FAPI-04, [18F]DPA-714, and [18F]MFBG, over 12 weeks. Fractional shortening (FS) was determined from the echocardiograms, and cardiac uptake of the radioligands was quantified from the PET images. Heart sections were collected and used for the analysis of bulk RNA-seq, RT-qPCR, Western blot, in situ hybridization (ISH), and histopathological analysis. Results: DOX mice exhibited cardiotoxicity and cardiac atrophy. Cardiac [68Ga]Ga-FAPI-04 PET signal was significantly higher in DOX mice from 2 weeks through the study endpoint. By contrast, no cardiac dysfunction was evident by echocardiography until 10 weeks, at which point FS was significantly reduced in DOX mice. There were no differences in [18F]DPA-714 and [18F]MFBG signals. Transcription and translation of FAP, but not TSPO or NET, was detected in cardiomyocytes and were elevated in the DOX hearts, in agreement with the PET data. Genes related to cell adhesion and extracellular remodeling were significantly upregulated in the DOX mice relative to controls. Conclusions: FAP is a sensitive and selective imaging biomarker for incipient cardiotoxicity and FAPI PET is a promising non-invasive imaging tool for identifying patients at risk of cardiotoxicity during or after anthracycline chemotherapy.

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Section: Discussionmentioning

confidence: 99%

PET imaging of fibroblast activation protein alpha (FAP) detects incipient cardiotoxicity due to anthracycline chemotherapy

Lee,

Manzo,

Rubinelli

et al. 2023

Preprint

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“…These include neuronal signaling, fibrosis, inflammation, amyloidosis, metabolic substrate utilization, and coronary artery plaques. These agents have great potential to address many clinical needs [ 35 , 38 ••, 39 – 41 ].…”

Section: New Pet Radiopharmaceuticals For Cardiac Studiesmentioning

confidence: 99%

Regulatory Agencies and PET/CT Imaging in the Clinic

Herscovitch

2022

Curr Cardiol Rep

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Purpose of Review The regulatory steps necessary to bring new PET radiopharmaceuticals to the clinic will be reviewed. The US Food and Drug Administration (FDA) provides approval to manufacture and use diagnostic radiopharmaceuticals, including those for cardiovascular PET/CT. Medicare not only provides insurance reimbursement for imaging procedures for its beneficiaries but also sets an example for third-party insurers to cover these procedures. Recent Findings FDA provides extensive guidance for performing studies to obtain the safety and efficacy data needed to approve PET radiopharmaceuticals, and the pace of approval has recently increased. There also has been considerable progress in insurance coverage for PET by Medicare. Several promising agents for cardiovascular PET imaging are in the development pipeline. Challenges remain, however, including low levels of reimbursement and the application of appropriate use criteria for imaging procedures. Summary It is important for cardiologists to understand the regulatory steps involved in translating PET radiopharmaceuticals to the clinic. Recent progress in both FDA approvals and Medicare coverage should facilitate the clinical use of new PET agents for molecular imaging of the heart.

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“…Additionally, for the visualization of the coronary artery lumen, as provided by invasive coronary angiography, CCTA enables the assessment of the coronary vessel wall, including quantification of plaque volume and composition and assessment of the presence of high-risk coronary plaque features ( 5 , 6 ), which have been described as pre-cursors of plaque rupture, causing acute coronary syndromes (ACS) ( 7 , 8 ). Finally, nuclear cardiac imaging techniques allow both the assessment of regional myocardial perfusion ( 9 , 10 ) and the unique opportunity to perform molecular cardiac imaging with different radiotracers directed towards different molecular targets ( 11 , 12 ).…”

mentioning

confidence: 99%