Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan 19;14(1):146.
doi: 10.3390/life14010146.

Induction of Arterial Inflammation by Immune Checkpoint Inhibitor Therapy in Lung Cancer Patients as Measured by 2-[18F]FDG Positron Emission Tomography/Computed Tomography Depends on Pre-Existing Vascular Inflammation

Raffaella Calabretta  1 , Lucian Beer  2 , Helmut Prosch  2 , Daria Kifjak  2   3 , Lucia Zisser  1 , Patrick Binder  1 , Stefan Grünert  1 , Werner Langsteger  1 , Xiang Li  1 , Marcus Hacker  1
Affiliations

Induction of Arterial Inflammation by Immune Checkpoint Inhibitor Therapy in Lung Cancer Patients as Measured by 2-[18F]FDG Positron Emission Tomography/Computed Tomography Depends on Pre-Existing Vascular Inflammation

Raffaella Calabretta et al. Life (Basel). .

Abstract

Background: Immune checkpoint inhibitors (ICI) are one of the most effective therapies in oncology, albeit associated with various immune-related adverse events also affecting the cardiovascular system.

Methods: We aimed to investigate the effect of ICI on arterial 2-[18F]FDG uptake by using 2-[18F]FDG PET/CT imaging pre/post treatment in 47 patients with lung cancer. Maximum 2-[18F]FDG standardized uptake values (SUVmax) and target-to-background ratios (TBRs) were calculated along six arterial segments. We classified the arterial PET lesions by pre-existing active inflammation (cut-off: TBRpre ≥ 1.6). 2-[18F]FDG metabolic activity pre/post treatment was also quantified in bone marrow, spleen, and liver. Circulating blood biomarkers were additionally collected at baseline and after immunotherapy.

Results: ICI treatment resulted in significantly increased arterial inflammatory activity, detected by increased TBRs, in all arterial PET lesions analyzed. In particular, a significant elevation of arterial 2-[18F]FDG uptake was only recorded in PET lesions without pre-existing inflammation, in calcified as well as in non-calcified lesions. Furthermore, a significant increase in arterial 2-[18F]FDG metabolic activity after immunotherapy was solely observed in patients not previously treated with chemotherapy or radiotherapy as well as in those without CV risk factors. No significant changes were recorded in either 2-[18F]FDG uptake of bone marrow, spleen and liver after treatment, or the blood biomarkers.

Conclusions: ICI induces vascular inflammation in lung cancer patients lacking pre-existing arterial inflammation.

Keywords: 2-[18F]FDG; PET; atherosclerosis; cardio-oncology; immune checkpoint inhibitors; lung cancer.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Representative 2-[18F]FDG PET/CT images. Increased arterial 2-[18F]FDG uptake (white arrows) after ICI therapy compared to baseline examination (pre-therapy) observed in transaxial (A) and in coronal (B) views. Abbreviations: CT, computed tomography; 2-[18F]FDG, 2-[18F]fluorodeoxyglucose; ICI, immune checkpoint inhibitors; PET, positron emission tomography.
Figure 2
Figure 2
Change in TBRs in arterial lesions after immunotherapy with ICI. (A) Significant increase in TBRs was found in all arterial lesion analyzed. In particular, TBR values were significantly higher in the lesions without pre-existing arterial inflammation as well as in both non-calcified and calcified lesions. (B) Change in TBRs in patients after ICI immunotherapy. Significant increase in TBRs was registered in all patients. In particular, TBRs were significantly elevated after ICI in all patients without previous CHT or RT. Abbreviations: CHT, chemotherapy; ICI, immune checkpoint inhibitors; RT, radiotherapy; TBR, target-to-background ratio. * Significance of p < 0.05.
Figure 3
Figure 3
2-[18F]FDG arterial metabolic activity after ICI therapy compared to baseline in patients previously treated with other anti-cancer therapies. No significant increase in arterial 2-[18F]FDG uptake after immunotherapy can be detected in a subject already treated with RT (A) as well as in a patient who earlier underwent CHT and RT (B). Abbreviations: CHT, chemotherapy; 2-[18F]FDG, 2-[18F]fluoro-d-glucose; ICI, immune checkpoint inhibitors; RT, radiotherapy.
Figure 4
Figure 4
Increased 2-[18F]FDG arterial uptake after ICI therapy compared to baseline in a subject without any other previous anti-cancer treatment. Cancer immunotherapy with ICI resulted in a modest but significant increase in arterial 2-[18F]FDG in a patient not previously treated with other anti-cancer therapies, such as CHT or RT. Abbreviations: CHT, chemotherapy; 2-[18F]FDG, 2-[18F]fluoro-d-glucose; ICI, immune checkpoint inhibitors; RT, radiotherapy.
Figure 5
Figure 5
(A) Comparison between the change in 2-[18F]FDG metabolic activity in bone marrow before and after ICI therapy. A significant decrease in metabolic activity in bone marrow, interpreted as SUVmax and SUVmean, was recorded in all patients previously treated with CHT or RT. (B) SLR after ICI therapy. A significant decrease in metabolic activity in bone marrow, interpreted as SUVmax and SUVmean, was recorded in all patients previously treated with CHT or RT. Abbreviations: CHT, chemotherapy; 2-[18F]FDG, 2-[18F]fluoro-d-glucose; ICI, immune checkpoint inhibitors; RT, radiotherapy; SLR, spleen-to-liver ratio; SUV, standardized uptake value. * Significance of p < 0.05.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Miller M.J., Foy K.C., Kaumaya P.T. Cancer immunotherapy: Present status, future perspective, and a new paradigm of peptide immunotherapeutics. Discov. Med. 2013;15:166–176. - PubMed
    1. Varricchi G., Marone G., Mercurio V., Galdiero M.R., Bonaduce D., Tocchetti C.G. Immune Checkpoint Inhibitors and Cardiac Toxicity: An Emerging Issue. Curr. Med. Chem. 2018;25:1327–1339. doi: 10.2174/0929867324666170407125017. - DOI - PubMed
    1. Ramos-Casals M., Brahmer J.R., Callahan M.K., Flores-Chávez A., Keegan N., Khamashta M.A., Lambotte O., Mariette X., Prat A., Suárez-Almazor M.E. Immune-related adverse events of checkpoint inhibitors. Nat. Rev. Dis. Primers. 2020;6:38. doi: 10.1038/s41572-020-0160-6. - DOI - PMC - PubMed
    1. Widakowich C., de Castro G., Jr., De Azambuja E., Dinh P., Awada A. Review: Side effects of approved molecular targeted therapies in solid cancers. Oncologist. 2007;12:1443–1455. doi: 10.1634/theoncologist.12-12-1443. - DOI - PubMed
    1. Zuppinger C., Suter T.M. Cancer therapy-associated cardiotoxicity and signaling in the myocardium. J. Cardiovasc. Pharmacol. 2010;56:141–146. doi: 10.1097/FJC.0b013e3181e0f89a. - DOI - PubMed

LinkOut - more resources