Novel Radiotracers for Molecular Imaging of Myocardial Inflammation: an Update Focused on Clinical Translation of Non-18F-FDG Radiotracers

Fleiner M, Kummer M, Mirlacher M, Sauter G, Cathomas G, Krapf R, Biedermann BC. Arterial neovascularization and inflammation in vulnerable patients: early and late signs of symptomatic atherosclerosis. Circulation. 2004;110(18):2843–50.

Article  PubMed  Google Scholar 

Benzer F, Kandemir FM, Ozkaraca M, Kucukler S, Caglayan C. Curcumin ameliorates doxorubicin-induced cardiotoxicity by abrogation of inflammation, apoptosis, oxidative DNA damage, and protein oxidation in rats. J Biochem Mol Toxicol. 2018;32(2): e22030.

Article  Google Scholar 

Dobaczewski M, Gonzalez-Quesada C, Frangogiannis NG. The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction. J Mol Cell Cardiol. 2010;48(3):504–11.

Article  CAS  PubMed  Google Scholar 

Kawai C. From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future. Circulation. 1999;99(8):1091–100.

Article  CAS  PubMed  Google Scholar 

Frangogiannis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res. 2002;53(1):31–47.

Article  CAS  PubMed  Google Scholar 

Shinde AV, Frangogiannis NG. Fibroblasts in myocardial infarction: a role in inflammation and repair. J Mol Cell Cardiol. 2014;70:74–82.

Article  CAS  PubMed  Google Scholar 

Bacmeister L, Schwarzl M, Warnke S, Stoffers B, Blankenberg S, Westermann D, Lindner D. Inflammation and fibrosis in murine models of heart failure. Basic Res Cardiol. 2019;114(3):1–35.

Article  CAS  Google Scholar 

Shirai T, Hilhorst M, Harrison DG, Goronzy JJ, Weyand CM. Macrophages in vascular inflammation–from atherosclerosis to vasculitis. Autoimmunity. 2015;48(3):139–51.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Leuschner F, Nahrendorf M. Molecular imaging of coronary atherosclerosis and myocardial infarction: considerations for the bench and perspectives for the clinic. Circ Res. 2011;108(5):593–606.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jaffer FA, Weissleder R. Seeing within: molecular imaging of the cardiovascular system. Circ Res. 2004;94(4):433–45.

Article  CAS  PubMed  Google Scholar 

Alanentalo T, Asayesh A, Morrison H, Lorén CE, Holmberg D, Sharpe J, Ahlgren U. Tomographic molecular imaging and 3D quantification within adult mouse organs. Nat Methods. 2007;4(1):31–3.

Article  CAS  PubMed  Google Scholar 

Mochizuki T, Tsukamoto E, Kuge Y, Kanegae K, Zhao S, Hikosaka K, Hosokawa M, Kohanawa M, Tamaki N. FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models. J Nucl Med. 2001;42(10):1551–5.

CAS  PubMed  Google Scholar 

Lobert P, Brown R, Dvorak R, Corbett J, Kazerooni E, Wong K. Spectrum of physiological and pathological cardiac and pericardial uptake of FDG in oncology PET-CT. Clin Radiol. 2013;68(1):e59–71.

Article  CAS  PubMed  Google Scholar 

Nensa F, Kloth J, Tezgah E, Poeppel TD, Heusch P, Goebel J, Nassenstein K, Schlosser T. Feasibility of FDG-PET in myocarditis: comparison to CMR using integrated PET/MRI. J Nucl Cardiol. 2018;25(3):785–94.

Article  PubMed  Google Scholar 

Okumura W, Iwasaki T, Toyama T, Iso T, Arai M, Oriuchi N, Endo K, Yokoyama T, Suzuki T, Kurabayashi M. Usefulness of fasting 18F-FDG PET in identification of cardiac sarcoidosis. J Nucl Med. 2004;45(12):1989–98.

PubMed  Google Scholar 

Lindholm P, Minn H, Leskinen-Kallio S, Bergman J, Ruotsalainen U, Joensuu H. Influence of the blood glucose concentration on FDG uptake in cancer—a PET study. J Nucl Med. 1993;34(1):1–6.

CAS  PubMed  Google Scholar 

Surasi DS, Bhambhvani P, Baldwin JA, Almodovar SE, O’Malley JP. 18F-FDG PET and PET/CT patient preparation: a review of the literature. J Nucl Med Technol. 2014;42(1):5–13.

Article  PubMed  Google Scholar 

Alvi RM, Young BD, Shahab Z, Pan H, Winkler J, Herzog E, Miller EJ. Repeatability and optimization of FDG positron emission tomography for evaluation of cardiac sarcoidosis. JACC Cardiovasc Imaging. 2019;12(7):1284–7. This paper revealed that variation in repeatability in PET sarcoid study was not related to the serum levels of glucose, insulin or free fatty acid measurements at the time of imaging.

Article  PubMed  Google Scholar 

ten Bokum AM, Hofland LJ, de Jong G, Bouma J, Melief MJ, Kwekkeboom DJ, Schonbrunn A, Mooy CM, Laman JD, Lamberts SW, et al. Immunohistochemical localization of somatostatin receptor sst2A in sarcoid granulomas. Eur J Clin Invest. 1999;29(7):630–6.

Article  PubMed  Google Scholar 

Rominger A, Saam T, Vogl E, Ubleis C, la Fougere C, Forster S, Haug A, Cumming P, Reiser MF, Nikolaou K, et al. In vivo imaging of macrophage activity in the coronary arteries using 68Ga-DOTATATE PET/CT: correlation with coronary calcium burden and risk factors. J Nucl Med. 2010;51(2):193–7.

Article  PubMed  Google Scholar 

Lambert JM, Lopez EF, Lindsey ML. Macrophage roles following myocardial infarction. Int J Cardiol. 2008;130(2):147–58.

Article  PubMed  PubMed Central  Google Scholar 

Smith WH, Nair RU, Adamson D, Kearney MT, Ball SG, Balmforth AJ. Somatostatin receptor subtype expression in the human heart: differential expression by myocytes and fibroblasts. J Endocrinol. 2005;187(3):379–86.

Article  CAS  PubMed  Google Scholar 

Sharma S, Singh AD, Sharma SK, Tripathi M, Das CJ, Kumar R. Gallium-68 DOTA-NOC PET/CT as an alternate predictor of disease activity in sarcoidosis. Nucl Med Commun. 2018;39(8):768–78.

Article  CAS  PubMed  Google Scholar 

Bravo PE, Bajaj N, Padera RF, Morgan V, Hainer J, Bibbo CF, Harrington M, Park M, Hyun H, Robertson M. Feasibility of somatostatin receptor-targeted imaging for detection of myocardial inflammation: a pilot study. J Nucl Cardiol. 2021;28(3):1089–99.

Article  PubMed  Google Scholar 

Gormsen LC, Haraldsen A, Kramer S, Dias AH, Kim WY, Borghammer P. A dual tracer (68)Ga-DOTANOC PET/CT and (18)F-FDG PET/CT pilot study for detection of cardiac sarcoidosis. EJNMMI Res. 2016;6(1):52.

Article  PubMed  PubMed Central  Google Scholar 

Vachatimanont S, Kunawudhi A, Promteangtrong C, Chotipanich C. Benefits of [(68)Ga]-DOTATATE PET-CT comparable to [(18)F]-FDG in patient with suspected cardiac sarcoidosis. J Nucl Cardiol. 2022;29(1):381–3. This case series reported superior accuracy for cardiac sarcoidosis of SSTR2 related PET comparing to 18F-FDG PET.

Article  PubMed  Google Scholar 

Imperiale A, Poindron V, Martinez M, Ohlmann P, Schindler TH, El Ghannudi S. 68Ga-DOTATOC PET for treatment efficacy evaluation of cardiac sarcoidosis. Clin Nucl Med. 2020;45(9):e416–8. This case series reported superior accuracy for cardiac sarcoidosis of SSTR2 related PET comparing to 18F-FDG PET.

Article  PubMed  Google Scholar 

Passah A, Kaushik P, Patel C, Parakh N. Gallium-68 DOTANOC scan in a patient with suspected cardiac sarcoidosis. J Nucl Cardiol. 2018;25(6):2177–8.

Article  PubMed  Google Scholar 

Boughdad S, Latifyan S, Fenwick C, Bouchaab H, Suffiotti M, Moslehi JJ, Salem JE, Schaefer N, Nicod-Lalonde M, Costes J, et al. (68) Ga-DOTATOC PET/CT to detect immune checkpoint inhibitor-related myocarditis. J Immunother Cancer. 2021;9(10):e003594. This case report described the applicability of 68Ga-DOTATOC to image myocarditis.

Article  PubMed  PubMed Central  Google Scholar 

Amini A, Dehdar F, Jafari E, Gholamrezanezhad A, Assadi M. Somatostatin receptor scintigraphy in a patient with myocarditis. Mol Imaging Radionucl Ther. 2021;30(1):50–3. This case report described the applicability of 68Ga-DOTATATE to image myocarditis.

Article  PubMed  PubMed Central  Google Scholar 

Polte CL, Bollano E, Oldfors A, Dudás A, Lagerstrand KM, Himmelman J, Bobbio E, Karason K, van Essen M, Bergh N. Somatostatin receptor positron emission tomography/computed tomography in giant cell myocarditis: a promising approach to molecular myocardial inflammation imaging. Circ: Cardiovasc Imaging. 2022;15(1):e013551. This case report described the applicability of SSTR2 related PET to image giant cell myocarditis.

PubMed  Google Scholar 

Bollano E, Bergh N, Dudás A, Bobbio E, Polte CL. Somatostatin receptor positron emission tomography/computed tomography in myocarditis following mRNA COVID-19 vaccination. Eur Heart J-Case Rep. 2022;6(4):ytac117. This case report described the applicability of SSTR2 related PET to image COVID-19 related myocarditis.

Article  PubMed  PubMed Central  Google Scholar 

Lapa C, Reiter T, Li X, Werner RA, Samnick S, Jahns R, Buck AK, Ertl G, Bauer WR. Imaging of myocardial inflammation with somatostatin receptor based PET/CT - a comparison to cardiac MRI. Int J Cardiol. 2015;194:44–9.

Article  PubMed  Google Scholar 

Hsia C-C, Lee T-S, Yeh C-H, Chen C-T, Peng C-L, Chen C-H, Hu P-A: The biological research of novel CXCR4 Agents [68Ga]-APD for evaluating the therapeutic efficacy of bromelain on atherosclerotic apolipoprotein E-deficient (ApoE-/-) mice. In.: Soc Nuclear Med. 2022;63(supplement 2):3335. The authors of this paper provide essential information a computer simulation designed compound as a Novel CXCR4 Agent, and its desirable accumulation in inflammatory myocardial lesions in animal studies.

Jujo K, Ii M, Sekiguchi H, Klyachko E, Misener S, Tanaka T, Tongers J, Roncalli J, Renault MA, Thorne T, et al. CXC-chemokine receptor 4 antagonist AMD3100 promotes cardiac functional recovery after ischemia/reperfusion injury via endothelial nitric oxide synthase-dependent mechanism. Circulation. 2013;127(1):63–73.

Article  CAS  PubMed  Google Scholar 

Wang Y, Dembowsky K, Chevalier E, Stuve P, Korf-Klingebiel M, Lochner M, Napp LC, Frank H, Brinkmann E, Kanwischer A, et al. C-X-C motif chemokine receptor 4 blockade promotes tissue repair after myocardial infarction by enhancing regulatory T cell mobilization and immune-regulatory function. Circulation. 2019;139(15):1798–812.

Article  PubMed  PubMed Central  Google Scholar 

Bengel FM, Ross TL. Emerging imaging targets for infiltrative cardiomyopathy: inflammation and fibrosis. J Nucl Cardiol. 2019;26(1):208–16.

Article  PubMed  Google Scholar 

Comments (0)

No login
gif