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Review Article
Originally Published 2 December 2024

In Vivo Cardiovascular Molecular Imaging: Contributions to Precision Medicine and Drug Development

Abstract

Conventional forms of noninvasive cardiovascular imaging that evaluate morphology, function, flow, and metabolism play a vital role in individual treatment decisions, often based on guidelines. Innovations in molecular imaging have enhanced our ability to spatially quantify the expression of a wider array of disease-related proteins, genes, or cell types, or the activity of specific pathogenic pathways. These techniques, which usually rely on design of targeted imaging probes, have already been used extensively in cancer medicine and have now become part of cardiovascular care in conditions such as amyloidosis and sarcoidosis. The recognition that common cardiovascular conditions are caused by a substantial diversity of pathobiologic pathways and the diversity of therapies available for use have rekindled interest in expanding the role of molecular imaging of tissue phenotype to improve precision in diagnosis and therapeutic decision-making. The intent of this article is to raise awareness and understanding of approaches to molecular or cellular imaging of phenotype with targeted probes, and their potential to promote the principles of precision medicine. Also addressed are the diverse roles of molecular imaging to improve precision and efficiency of new drug development at the stages of candidate identification, preclinical testing, and clinical trials.

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References

1.
Denny JC, Collins FS. Precision medicine in 2030: seven ways to transform healthcare. Cell. 2021;184:1415–1419. doi: 10.1016/j.cell.2021.01.015
2.
Lindner JR, Sinusas A. Molecular imaging in cardiovascular disease: which methods, which diseases? J Nucl Cardiol. 2013;20:990–1001. doi: 10.1007/s12350-013-9785-0
3.
Nahrendorf M, Sosnovik DE, French BA, Swirski FK, Bengel F, Sadeghi MM, Lindner JR, Wu JC, Kraitchman DL, Fayad ZA, et al. Multimodality cardiovascular molecular imaging, part II. Circ Cardiovasc Imaging. 2009;2:56–70. doi: 10.1161/CIRCIMAGING.108.839092
4.
Zhu A, Lee D, Shim H. Metabolic positron emission tomography imaging in cancer detection and therapy response. Semin Oncol. 2011;38:55–69. doi: 10.1053/j.seminoncol.2010.11.012
5.
Buck AK, Reske SN. Cellular origin and molecular mechanisms of 18F-FDG uptake: is there a contribution of the endothelium? J Nucl Med. 2004;45:461–463.
6.
Peppicelli S, Andreucci E, Ruzzolini J, Bianchini F, Calorini L. FDG uptake in cancer: a continuing debate. Theranostics. 2020;10:2944–2948. doi: 10.7150/thno.40599
7.
Zaha DC. Significance of immunohistochemistry in breast cancer. World J Clin Oncol. 2014;5:382–392. doi: 10.5306/wjco.v5.i3.382
8.
Gebhart G, Lamberts LE, Wimana Z, Garcia C, Emonts P, Ameye L, Stroobants S, Huizing M, Aftimos P, Tol J, et al. Molecular imaging as a tool to investigate heterogeneity of advanced HER2-positive breast cancer and to predict patient outcome under trastuzumab emtansine (T-DM1): the ZEPHIR trial. Ann Oncol. 2016;27:619–624. doi: 10.1093/annonc/mdv577
9.
Miladinova D. Molecular imaging of HER2 receptor: targeting HER2 for imaging and therapy in nuclear medicine. Front Mol Biosci. 2023;10:1144817. doi: 10.3389/fmolb.2023.1144817
10.
Wei W, Ni D, Ehlerding EB, Luo QY, Cai W. PET imaging of receptor tyrosine kinases in cancer. Mol Cancer Ther. 2018;17:1625–1636. doi: 10.1158/1535-7163.MCT-18-0087
11.
Lauri C, Varani M, Bentivoglio V, Capriotti G, Signore A. Present status and future trends in molecular imaging of lymphocytes. Semin Nucl Med. 2023;53:125–134. doi: 10.1053/j.semnuclmed.2022.08.011
12.
Lehtonen J, Uusitalo V, Poyhonen P, Mayranpaa MI, Kupari M. Cardiac sarcoidosis: phenotypes, diagnosis, treatment, and prognosis. Eur Heart J. 2023;44:1495–1510. doi: 10.1093/eurheartj/ehad067
13.
Blankstein R, Divakaran S. Treating myocardial inflammation in cardiac sarcoidosis: why, with what, and for how long? JACC Cardiovasc Imaging. 2022;15:1956–1959. doi: 10.1016/j.jcmg.2022.07.016
14.
Bravo PE, Singh A, Di Carli MF, Blankstein R. Advanced cardiovascular imaging for the evaluation of cardiac sarcoidosis. J Nucl Cardiol. 2019;26:188–199. doi: 10.1007/s12350-018-01488-9
15.
Perel-Winkler A, Bokhari S, Perez-Recio T, Zartoshti A, Askanase A, Geraldino-Pardilla L. Myocarditis in systemic lupus erythematosus diagnosed by (18)F-fluorodeoxyglucose positron emission tomography. Lupus Sci Med. 2018;5:e000265. doi: 10.1136/lupus-2018-000265
16.
Ekstrom K, Lehtonen J, Kandolin R, Raisanen-Sokolowski A, Salmenkivi K, Kupari M. Incidence, risk factors, and outcome of life-threatening ventricular arrhythmias in giant cell myocarditis. Circ Arrhythm Electrophysiol. 2016;9:004559.
17.
Marschner CA, Thavendiranathan P, Gustafson D, Howe KL, Fish JE, Iwanochko RM, Wald RM, Abdel-Qadir H, Epelman S, Cheung AM, et al. Myocardial inflammation on FDG PET/MRI and clinical outcomes in symptomatic and asymptomatic participants after COVID-19 vaccination. Radiol Cardiothorac Imaging. 2023;5:e220247. doi: 10.1148/ryct.220247
18.
Corbett JR, Lewis SE, Wolfe CL, Jansen DE, Lewis M, Rellas JS, Parkey RW, Rude RE, Buja LM, Willerson JT. Measurement of myocardial infarct size by technetium pyrophosphate single-photon tomography. Am J Cardiol. 1984;54:1231–1236. doi: 10.1016/s0002-9149(84)80072-7
19.
Kittleson MM, Panjrath GS, Amancherla K, Davis LL, Deswal A, Dixon DL, Januzzi JL, Yancy CW. 2023 ACC Expert consensus decision pathway on management of heart failure with preserved ejection fraction: a report of the American College of Cardiology solution set oversight committee. J Am Coll Cardiol. 2023;81:1835–1878. doi: 10.1016/j.jacc.2023.03.393
20.
Poterucha TJ, Elias P, Bokhari S, Einstein AJ, DeLuca A, Kinkhabwala M, Johnson LL, Flaherty KR, Saith SE, Griffin JM, et al. Diagnosing transthyretin cardiac amyloidosis by technetium Tc 99m pyrophosphate: a test in evolution. JACC Cardiovasc Imaging. 2021;14:1221–1231. doi: 10.1016/j.jcmg.2020.08.027
21.
Bokhari S, Castano A, Pozniakoff T, Deslisle S, Latif F, Maurer MS. (99m)Tc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses. Circ Cardiovasc Imaging. 2013;6:195–201. doi: 10.1161/CIRCIMAGING.112.000132
22.
Yu AL, Chen YC, Tsai CH, Wu YA, Su MY, Chou CH, Shun CT, Hsueh HW, Juang JJ, Lee MJ, et al. Use of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography in monitoring therapeutic changes of eplontersen in patients with hereditary transthyretin amyloid cardiomyopathy. J Am Heart Assoc. 2024;13:e030512. doi: 10.1161/JAHA.123.030512
23.
Stats MA, Stone JR. Varying levels of small microcalcifications and macrophages in ATTR and AL cardiac amyloidosis: implications for utilizing nuclear medicine studies to subtype amyloidosis. Cardiovasc Pathol. 2016;25:413–417. doi: 10.1016/j.carpath.2016.07.001
24.
Glasenapp A, Hess A, Thackeray JT. Molecular imaging in nuclear cardiology: pathways to individual precision medicine. J Nucl Cardiol. 2020;27:2195–2201. doi: 10.1007/s12350-020-02319-6
25.
Davidson BP, Hodovan J, Layoun ME, Golwala H, Zahr F, Lindner JR. Echocardiographic ischemic memory molecular imaging for point-of-care detection of myocardial ischemia. J Am Coll Cardiol. 2021;78:1990–2000. doi: 10.1016/j.jacc.2021.08.068
26.
Shim CY, Liu YN, Atkinson T, Xie A, Foster T, Davidson BP, Treible M, Qi Y, Lopez JA, Munday A, et al. Molecular imaging of platelet-endothelial interactions and endothelial von Willebrand factor in early and mid-stage atherosclerosis. Circ Cardiovasc Imaging. 2015;8:e002765. doi: 10.1161/CIRCIMAGING.114.002765
27.
Ishino S, Mukai T, Kuge Y, Kume N, Ogawa M, Takai N, Kamihashi J, Shiomi M, Minami M, Kita T, et al. Targeting of lectinlike oxidized low-density lipoprotein receptor 1 (LOX-1) with 99mTc-labeled anti-LOX-1 antibody: potential agent for imaging of vulnerable plaque. J Nucl Med. 2008;49:1677–1685. doi: 10.2967/jnumed.107.049536
28.
Li D, Patel AR, Klibanov AL, Kramer CM, Ruiz M, Kang BY, Mehta JL, Beller GA, Glover DK, Meyer CH. Molecular imaging of atherosclerotic plaques targeted to oxidized LDL receptor LOX-1 by SPECT/CT and magnetic resonance. Circ Cardiovasc Imaging. 2010;3:464–472. doi: 10.1161/CIRCIMAGING.109.896654
29.
Lipinski MJ, Amirbekian V, Frias JC, Aguinaldo JG, Mani V, Briley-Saebo KC, Fuster V, Fallon JT, Fisher EA, Fayad ZA. MRI to detect atherosclerosis with gadolinium-containing immunomicelles targeting the macrophage scavenger receptor. Magn Reson Med. 2006;56:601–610. doi: 10.1002/mrm.20995
30.
Ayala-Lopez W, Xia W, Varghese B, Low PS. Imaging of atherosclerosis in apolipoprotein E knockout mice: targeting of a folate-conjugated radiopharmaceutical to activated macrophages. J Nucl Med. 2010;51:768–774. doi: 10.2967/jnumed.109.071324
31.
Swirski FK, Nahrendorf M. Imaging macrophage development and fate in atherosclerosis and myocardial infarction. Immunol Cell Biol. 2013;91:297–303. doi: 10.1038/icb.2012.72
32.
Sahul ZH, Mukherjee R, Song J, McAteer J, Stroud RE, Dione DP, Staib L, Papademetris X, Dobrucki LW, Duncan JS, et al. Targeted imaging of the spatial and temporal variation of matrix metalloproteinase activity in a porcine model of postinfarct remodeling: relationship to myocardial dysfunction. Circ Cardiovasc Imaging. 2011;4:381–391. doi: 10.1161/CIRCIMAGING.110.961854
33.
Su H, Spinale FG, Dobrucki LW, Song J, Hua J, Sweterlitsch S, Dione DP, Cavaliere P, Chow C, Bourke BN, et al. Noninvasive targeted imaging of matrix metalloproteinase activation in a murine model of postinfarction remodeling. Circulation. 2005;112:3157–3167. doi: 10.1161/CIRCULATIONAHA.105.583021
34.
Kontos MC, Dilsizian V, Weiland F, DePuey G, Mahmarian JJ, Iskandrian AE, Bateman TM, Heller GV, Ananthasubramaniam K, Li Y, et al. Iodofiltic acid I 123 (BMIPP) fatty acid imaging improves initial diagnosis in emergency department patients with suspected acute coronary syndromes: a multicenter trial. J Am Coll Cardiol. 2010;56:290–299. doi: 10.1016/j.jacc.2010.03.045
35.
Lamacie MM, Almufleh A, Nair V, Stadnick E, Birnie D, Beanlands RSB, Chih S. Serial (18)F-fluorodeoxyglucose positron emission tomography imaging in a patient with giant cell myocarditis. Circ Cardiovasc Imaging. 2020;13:e009940. doi: 10.1161/CIRCIMAGING.119.009940
36.
Polte CL, Bobbio E, Bollano E, Bergh N, Polte C, Himmelman J, Lagerstrand KM, Gao SA. Cardiovascular magnetic resonance in myocarditis. Diagnostics (Basel). 2022;12:399. doi: 10.3390/diagnostics12020399
37.
Miller RJH, Thomson L, Levine R, Dimbil SJ, Patel J, Kobashigawa JA, Kransdorf E, Li D, Berman DS, Tamarappoo B. Quantitative myocardial tissue characterization by cardiac magnetic resonance in heart transplant patients with suspected cardiac rejection. Clin Transplant. 2019;33:e13704. doi: 10.1111/ctr.13704
38.
Kotanidis CP, Bazmpani MA, Haidich AB, Karvounis C, Antoniades C, Karamitsos TD. Diagnostic accuracy of cardiovascular magnetic resonance in acute myocarditis: a systematic review and meta-analysis. JACC Cardiovasc Imaging. 2018;11:1583–1590. doi: 10.1016/j.jcmg.2017.12.008
39.
Bohnen S, Radunski UK, Lund GK, Kandolf R, Stehning C, Schnackenburg B, Adam G, Blankenberg S, Muellerleile K. Performance of t1 and t2 mapping cardiovascular magnetic resonance to detect active myocarditis in patients with recent-onset heart failure. Circ Cardiovasc Imaging. 2015;8:e003073. doi: 10.1161/CIRCIMAGING.114.003073
40.
Hang W, Chen C, Seubert JM, Wang DW. Fulminant myocarditis: a comprehensive review from etiology to treatments and outcomes. Signal Transduct Target Ther. 2020;5:287. doi: 10.1038/s41392-020-00360-y
41.
Pollack A, Kontorovich AR, Fuster V, Dec GW. Viral myocarditis: diagnosis, treatment options, and current controversies. Nat Rev Cardiol. 2015;12:670–680. doi: 10.1038/nrcardio.2015.108
42.
MacRitchie N, Noonan J, Guzik TJ, Maffia P. Molecular imaging of cardiovascular inflammation. Br J Pharmacol. 2021;178:4216–4245. doi: 10.1111/bph.15654
43.
Shi T, Miller EJ. Novel radiotracers for molecular imaging of myocardial inflammation: an update focused on clinical translation of non-18F-FDG radiotracers. Curr Cardiovasc Imaging Rep. 2023;16:1–9. doi: 10.1007/s12410-023-09574-4
44.
Chaudhry F, Adapoe M, Johnson KW, Narula N, Shekhar A, Kawai H, Horwitz JK, Liu J, Li Y, Pak KY, et al. Molecular imaging of cardiac allograft rejection: targeting apoptosis with radiolabeled duramycin. JACC Cardiovasc Imaging. 2020;13:1438–1441. doi: 10.1016/j.jcmg.2020.01.010
45.
Steinl DC, Xu L, Khanicheh E, Ellertsdottir E, Ochoa-Espinosa A, Mitterhuber M, Glatz K, Kuster GM, Kaufmann BA. Noninvasive contrast-enhanced ultrasound molecular imaging detects myocardial inflammatory response in autoimmune myocarditis. Circ Cardiovasc Imaging. 2016;9:004720.
46.
Lindner JR. Molecular imaging of vascular phenotype in cardiovascular disease: new diagnostic opportunities on the horizon. J Am Soc Echocardiogr. 2010;23:343–50; quiz 450. doi: 10.1016/j.echo.2010.01.025
47.
Konishi M, Erdem SS, Weissleder R, Lichtman AH, McCarthy JR, Libby P. Imaging granzyme B activity assesses immune-mediated myocarditis. Circ Res. 2015;117:502–512. doi: 10.1161/CIRCRESAHA.115.306364
48.
Figueroa AL, Abdelbaky A, Truong QA, Corsini E, MacNabb MH, Lavender ZR, Lawler MA, Grinspoon SK, Brady TJ, Nasir K, et al. Measurement of arterial activity on routine FDG PET/CT images improves prediction of risk of future CV events. JACC Cardiovasc Imaging. 2013;6:1250–1259. doi: 10.1016/j.jcmg.2013.08.006
49.
Mayer M, Borja AJ, Hancin EC, Auslander T, Revheim ME, Moghbel MC, Werner TJ, Alavi A, Rajapakse CS. Imaging atherosclerosis by PET, with emphasis on the role of FDG and NaF as potential biomarkers for this disorder. Front Physiol. 2020;11:511391. doi: 10.3389/fphys.2020.511391
50.
Tarkin JM, Joshi FR, Evans NR, Chowdhury MM, Figg NL, Shah AV, Starks LT, Martin-Garrido A, Manavaki R, Yu E, et al. Detection of atherosclerotic inflammation by (68)Ga-DOTATATE PET compared to [(18)F]FDG PET imaging. J Am Coll Cardiol. 2017;69:1774–1791. doi: 10.1016/j.jacc.2017.01.060
51.
Kwiecinski J, Tzolos E, Adamson PD, Cadet S, Moss AJ, Joshi N, Williams MC, van Beek EJR, Dey D, Berman DS, et al. Coronary (18)F-sodium fluoride uptake predicts outcomes in patients with coronary artery disease. J Am Coll Cardiol. 2020;75:3061–3074. doi: 10.1016/j.jacc.2020.04.046
52.
Hoilund-Carlsen PF, Sturek M, Alavi A, Gerke O. Atherosclerosis imaging with (18)F-sodium fluoride PET: state-of-the-art review. Eur J Nucl Med Mol Imaging. 2020;47:1538–1551. doi: 10.1007/s00259-019-04603-1
53.
Kaufmann BA, Carr CL, Belcik JT, Xie A, Yue Q, Chadderdon S, Caplan ES, Khangura J, Bullens S, Bunting S, et al. Molecular imaging of the initial inflammatory response in atherosclerosis: implications for early detection of disease. Arterioscler Thromb Vasc Biol. 2010;30:54–59. doi: 10.1161/ATVBAHA.109.196386
54.
Chadderdon SM, Belcik JT, Bader L, Kirigiti MA, Peters DM, Kievit P, Grove KL, Lindner JR. Proinflammatory endothelial activation detected by molecular imaging in obese nonhuman primates coincides with onset of insulin resistance and progressively increases with duration of insulin resistance. Circulation. 2014;129:471–478. doi: 10.1161/CIRCULATIONAHA.113.003645
55.
Kim JB, Park K, Ryu J, Lee JJ, Lee MW, Cho HS, Nam HS, Park OK, Song JW, Kim TS, et al. Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors. Sci Rep. 2016;6:22608. doi: 10.1038/srep22608
56.
Quillard T, Libby P. Molecular imaging of atherosclerosis for improving diagnostic and therapeutic development. Circ Res. 2012;111:231–244. doi: 10.1161/CIRCRESAHA.112.268144
57.
Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, et al; CANTOS Trial Group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–1131. doi: 10.1056/NEJMoa1707914
58.
Abbate A, Trankle CR, Buckley LF, Lipinski MJ, Appleton D, Kadariya D, Canada JM, Carbone S, Roberts CS, Abouzaki N, et al. Interleukin-1 blockade inhibits the acute inflammatory response in patients with ST-segment-elevation myocardial infarction. J Am Heart Assoc. 2020;9:e014941. doi: 10.1161/JAHA.119.014941
59.
Ridker PM, MacFadyen JG, Thuren T, Libby P. Residual inflammatory risk associated with interleukin-18 and interleukin-6 after successful interleukin-1beta inhibition with canakinumab: further rationale for the development of targeted anti-cytokine therapies for the treatment of atherothrombosis. Eur Heart J. 2020;41:2153–2163. doi: 10.1093/eurheartj/ehz542
60.
Kola I, Bell J. A call to reform the taxonomy of human disease. Nat Rev Drug Discov. 2011;10:641–642. doi: 10.1038/nrd3534
61.
Speidl WS, Kastl SP, Huber K, Wojta J. Complement in atherosclerosis: friend or foe? J Thromb Haemost. 2011;9:428–440. doi: 10.1111/j.1538-7836.2010.04172.x
62.
Mallat Z, Binder CJ. The why and how of adaptive immune responses in ischemic cardiovascular disease. Nat Cardiovasc Res. 2022;1:431–444. doi: 10.1038/s44161-022-00049-1
63.
Sage AP, Tsiantoulas D, Binder CJ, Mallat Z. The role of B cells in atherosclerosis. Nat Rev Cardiol. 2019;16:180–196. doi: 10.1038/s41569-018-0106-9
64.
Nording HM, Seizer P, Langer HF. Platelets in inflammation and atherogenesis. Front Immunol. 2015;6:98. doi: 10.3389/fimmu.2015.00098
65.
Wu MD, Atkinson TM, Lindner JR. Platelets and von Willebrand factor in atherogenesis. Blood. 2017;129:1415–1419. doi: 10.1182/blood-2016-07-692673
66.
Ketelhuth DF, Hansson GK. Adaptive response of T and B cells in atherosclerosis. Circ Res. 2016;118:668–678. doi: 10.1161/CIRCRESAHA.115.306427
67.
Barrett TJ. Macrophages in atherosclerosis regression. Arterioscler Thromb Vasc Biol. 2020;40:20–33. doi: 10.1161/ATVBAHA.119.312802
68.
Mueller PA, Zhu L, Tavori H, Huynh K, Giunzioni I, Stafford JM, Linton MF, Fazio S. Deletion of macrophage low-density lipoprotein receptor-related protein 1 (LRP1) accelerates atherosclerosis regression and increases C-C chemokine receptor type 7 (CCR7) expression in plaque macrophages. Circulation. 2018;138:1850–1863. doi: 10.1161/CIRCULATIONAHA.117.031702
69.
Scirica BM, Bergmark BA, Morrow DA, Antman EM, Bonaca MP, Murphy SA, Sabatine MS, Braunwald E, Wiviott SD. Nonculprit lesion myocardial infarction following percutaneous coronary intervention in patients with acute coronary syndrome. J Am Coll Cardiol. 2020;75:1095–1106. doi: 10.1016/j.jacc.2019.12.067
70.
Stone GW, Maehara A, Lansky AJ, de Bruyne B, Cristea E, Mintz GS, Mehran R, McPherson J, Farhat N, Marso SP, et al; PROSPECT Investigators. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011;364:226–235. doi: 10.1056/NEJMoa1002358
71.
Dutta P, Courties G, Wei Y, Leuschner F, Gorbatov R, Robbins CS, Iwamoto Y, Thompson B, Carlson AL, Heidt T, et al. Myocardial infarction accelerates atherosclerosis. Nature. 2012;487:325–329. doi: 10.1038/nature11260
72.
Moccetti F, Brown E, Xie A, Packwood W, Qi Y, Ruggeri Z, Shentu W, Chen J, Lopez JA, Lindner JR. Myocardial infarction produces sustained proinflammatory endothelial activation in remote arteries. J Am Coll Cardiol. 2018;72:1015–1026. doi: 10.1016/j.jacc.2018.06.044
73.
Ozawa K, Packwood W, Varlamov O, Muller MA, Xie A, Wu M, Abraham-Fan R, Lopez JA, Lindner JR. Elevated low-density lipoprotein cholesterol increases microvascular endothelial von Willebrand factor and thromboinflammation after myocardial infarction. Arterioscler Thromb Vasc Biol. 2023;43:1041–1053. doi: 10.1161/ATVBAHA.122.318884
74.
Moccetti F, Belcik T, Latifi Y, Xie A, Ozawa K, Brown E, Davidson BP, Packwood W, Ammi A, Huke S, et al. Flow augmentation in the myocardium by ultrasound cavitation of microbubbles: role of shear-mediated purinergic signaling. J Am Soc Echocardiogr. 2020;33:1023–1031.e2. doi: 10.1016/j.echo.2020.03.016
75.
Shentu W, Ozawa K, Nguyen TA, Wu MD, Packwood W, Xie A, Muller MA, Brown E, Hagen MW, Lopez JA, et al. Echocardiographic molecular imaging of the effect of anticytokine therapy for atherosclerosis. J Am Soc Echocardiogr. 2021;34:433–442.e3. doi: 10.1016/j.echo.2020.11.012
76.
Stendahl JC, Kwan JM, Pucar D, Sadeghi MM. Radiotracers to address unmet clinical needs in cardiovascular imaging, part 2: inflammation, fibrosis, thrombosis, calcification, and amyloidosis imaging. J Nucl Med. 2022;63:986–994. doi: 10.2967/jnumed.121.263507
77.
Saraste A, Stahle M, Roivainen A, Knuuti J. Molecular imaging of heart failure: an update and future trends. Semin Nucl Med. 2024;54:674–685. doi: 10.1053/j.semnuclmed.2024.03.005
78.
Werner RA, Koenig T, Diekmann J, Haghikia A, Derlin T, Thackeray JT, Napp LC, Wester HJ, Ross TL, Schaefer A, et al. CXCR4-targeted imaging of post-infarct myocardial tissue inflammation: prognostic value after reperfused myocardial infarction. JACC Cardiovasc Imaging. 2022;15:372–374. doi: 10.1016/j.jcmg.2021.08.013
79.
Varasteh Z, Weber WA, Rischpler C. Nuclear molecular imaging of cardiac remodeling after myocardial infarction. Pharmaceuticals (Basel). 2022;15:183. doi: 10.3390/ph15020183
80.
Wang L, Wang Y, Wang J, Xiao M, Xi XY, Chen BX, Su Y, Zhang Y, Xie B, Dong Z, et al. Myocardial activity at (18)F-FAPI PET/CT and risk for sudden cardiac death in hypertrophic cardiomyopathy. Radiology. 2023;306:e221052. doi: 10.1148/radiol.221052
81.
Higuchi T, Serfling SE, Leistner DM, Speer T, Werner RA. FAPI-PET in cardiovascular disease. Semin Nucl Med. 2024;54:747–752. doi: 10.1053/j.semnuclmed.2024.02.006.
82.
Treutlein C, Distler JHW, Tascilar K, Fakhouri SC, Gyorfi AH, Atzinger A, Matei AE, Dees C, Buttner-Herold M, Kuwert T, et al. Assessment of myocardial fibrosis in patients with systemic sclerosis using [(68)Ga]Ga-FAPI-04-PET-CT. Eur J Nucl Med Mol Imaging. 2023;50:1629–1635. doi: 10.1007/s00259-022-06081-4
83.
Hughes JP, Rees S, Kalindjian SB, Philpott KL. Principles of early drug discovery. Br J Pharmacol. 2011;162:1239–1249. doi: 10.1111/j.1476-5381.2010.01127.x
84.
Macarron R, Banks MN, Bojanic D, Burns DJ, Cirovic DA, Garyantes T, Green DV, Hertzberg RP, Janzen WP, Paslay JW, et al. Impact of high-throughput screening in biomedical research. Nat Rev Drug Discov. 2011;10:188–195. doi: 10.1038/nrd3368
85.
Paul SM, Mytelka DS, Dunwiddie CT, Persinger CC, Munos BH, Lindborg SR, Schacht AL. How to improve R&D productivity: the pharmaceutical industry’s grand challenge. Nat Rev Drug Discov. 2010;9:203–214. doi: 10.1038/nrd3078
86.
Naci H, Carter AW, Mossialos E. Why the drug development pipeline is not delivering better medicines. BMJ. 2015;351:h5542. doi: 10.1136/bmj.h5542
87.
van de Donk PP, Kist de Ruijter L, Lub-de Hooge MN, Brouwers AH, van der Wekken AJ, Oosting SF, Fehrmann RS, de Groot DJA, de Vries EG. Molecular imaging biomarkers for immune checkpoint inhibitor therapy. Theranostics. 2020;10:1708–1718. doi: 10.7150/thno.38339
88.
Politis M. Neuroimaging in Parkinson disease: from research setting to clinical practice. Nat Rev Neurol. 2014;10:708–722. doi: 10.1038/nrneurol.2014.205
89.
Jaffer FA, Kim DE, Quinti L, Tung CH, Aikawa E, Pande AN, Kohler RH, Shi GP, Libby P, Weissleder R. Optical visualization of cathepsin K activity in atherosclerosis with a novel, protease-activatable fluorescence sensor. Circulation. 2007;115:2292–2298. doi: 10.1161/CIRCULATIONAHA.106.660340
90.
Quillard T, Croce K, Jaffer FA, Weissleder R, Libby P. Molecular imaging of macrophage protease activity in cardiovascular inflammation in vivo. Thromb Haemost. 2011;105:828–836. doi: 10.1160/TH10-09-0589
91.
Zhang J, Nie L, Razavian M, Ahmed M, Dobrucki LW, Asadi A, Edwards DS, Azure M, Sinusas AJ, Sadeghi MM. Molecular imaging of activated matrix metalloproteinases in vascular remodeling. Circulation. 2008;118:1953–1960. doi: 10.1161/CIRCULATIONAHA.108.789743
92.
Aikawa E, Nahrendorf M, Sosnovik D, Lok VM, Jaffer FA, Aikawa M, Weissleder R. Multimodality molecular imaging identifies proteolytic and osteogenic activities in early aortic valve disease. Circulation. 2007;115:377–386. doi: 10.1161/CIRCULATIONAHA.106.654913
93.
Tahara N, Mukherjee J, de Haas HJ, Petrov AD, Tawakol A, Haider N, Tahara A, Constantinescu CC, Zhou J, Boersma HH, et al. 2-deoxy-2-[18F]fluoro-D-mannose positron emission tomography imaging in atherosclerosis. Nat Med. 2014;20:215–219. doi: 10.1038/nm.3437
94.
Liu Y, Davidson BP, Yue Q, Belcik T, Xie A, Inaba Y, McCarty OJ, Tormoen GW, Zhao Y, Ruggeri ZM, et al. Molecular imaging of inflammation and platelet adhesion in advanced atherosclerosis effects of antioxidant therapy with NADPH oxidase inhibition. Circ Cardiovasc Imaging. 2013;6:74–82. doi: 10.1161/CIRCIMAGING.112.975193
95.
Winter PM, Caruthers SD, Zhang H, Williams TA, Wickline SA, Lanza GM. Antiangiogenic synergism of integrin-targeted fumagillin nanoparticles and atorvastatin in atherosclerosis. JACC Cardiovasc Imaging. 2008;1:624–634. doi: 10.1016/j.jcmg.2008.06.003
96.
Ryu JC, Davidson BP, Xie A, Qi Y, Zha D, Belcik JT, Caplan ES, Woda JM, Hedrick CC, Hanna RN, et al. Molecular imaging of the paracrine proangiogenic effects of progenitor cell therapy in limb ischemia. Circulation. 2013;127:710–719. doi: 10.1161/CIRCULATIONAHA.112.116103
97.
Winter PM, Caruthers SD, Allen JS, Cai K, Williams TA, Lanza GM, Wickline SA. Molecular imaging of angiogenic therapy in peripheral vascular disease with alphanubeta3-integrin-targeted nanoparticles. Magn Reson Med. 2010;64:369–376. doi: 10.1002/mrm.22447
98.
Cunha L, Szigeti K, Mathe D, Metello LF. The role of molecular imaging in modern drug development. Drug Discov Today. 2014;19:936–948. doi: 10.1016/j.drudis.2014.01.003
99.
Liu J, Narsinh KH, Lan F, Wang L, Nguyen PK, Hu S, Lee A, Han L, Gong Y, Huang M, et al. Early stem cell engraftment predicts late cardiac functional recovery: preclinical insights from molecular imaging. Circ Cardiovasc Imaging. 2012;5:481–490. doi: 10.1161/CIRCIMAGING.111.969329
100.
Greene SJ, Mentz RJ, Fiuzat M, Butler J, Solomon SD, Ambrosy AP, Mehta C, Teerlink JR, Zannad F, O’Connor CM. Reassessing the role of surrogate end points in drug development for heart failure. Circulation. 2018;138:1039–1053. doi: 10.1161/CIRCULATIONAHA.118.034668
101.
Fordyce CB, Roe MT, Ahmad T, Libby P, Borer JS, Hiatt WR, Bristow MR, Packer M, Wasserman SM, Braunstein N, et al. Cardiovascular drug development: is it dead or just hibernating? J Am Coll Cardiol. 2015;65:1567–1582. doi: 10.1016/j.jacc.2015.03.016
102.
Tarkin JM, Dweck MR, Rudd JHF. Imaging as a surrogate marker of drug efficacy in cardiovascular disease. Heart. 2019;105:567–578. doi: 10.1136/heartjnl-2017-311213
103.
Fayad ZA, Mani V, Woodward M, Kallend D, Abt M, Burgess T, Fuster V, Ballantyne CM, Stein EA, Tardif JC, et al; dal-PLAQUE Investigators. Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging (dal-PLAQUE): a randomised clinical trial. Lancet. 2011;378:1547–1559. doi: 10.1016/S0140-6736(11)61383-4
104.
Hoogeveen RM, Opstal TSJ, Kaiser Y, Stiekema LCA, Kroon J, Knol RJJ, Bax WA, Verberne HJ, Cornel JH, Stroes ESG. PCSK9 antibody alirocumab attenuates arterial wall inflammation without changes in circulating inflammatory markers. JACC Cardiovasc Imaging. 2019;12:2571–2573. doi: 10.1016/j.jcmg.2019.06.022
105.
Stiekema LCA, Stroes ESG, Verweij SL, Kassahun H, Chen L, Wasserman SM, Sabatine MS, Mani V, Fayad ZA. Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin/kexin type 9 antibody treatment. Eur Heart J. 2019;40:2775–2781. doi: 10.1093/eurheartj/ehy862

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Published In

Go to Circulation
Go to Circulation
Circulation
Pages: 1885 - 1897
PubMed: 39621762

History

Published online: 2 December 2024
Published in print: 3 December 2024

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Keywords

  1. drug discovery
  2. molecular imaging
  3. precision medicine

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Affiliations

Cardiovascular Division and Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville.
Cardiovascular Division and Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville.

Notes

For Sources of Funding and Disclosures, see page 1894.
Circulation is available at www.ahajournals.org/journal/circ
Correspondence to: Jonathan R. Lindner, MD, Robert M. Berne Cardiovascular Research Center, 415 Lane Rd, Box 801394, Charlottesville, VA 22908. Email [email protected]

Disclosures

None.

Sources of Funding

Dr Lindner is supported by grants R01-HL078610, R01-HL130046, R01-HL171377, and R01-HL165422 from the National Institutes of Health, grant 23TPA1077712 from the American Heart Association, and grant 18-18HCFBP_2-0009 from the National Aeronautics and Space Agency, and has investigator-initiated grants from Lantheus Medical Imaging.

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In Vivo Cardiovascular Molecular Imaging: Contributions to Precision Medicine and Drug Development
Circulation
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