Vascular adhesion protein-1-targeted PET imaging in autoimmune myocarditis

Arghavan Jahandideh; Jenni Virta; Xiang-Guo Li; Heidi Liljenbäck; Olli Moisio; Jesse Ponkamo; Noora Rajala; Marion Alix; Jukka Lehtonen; Mikko I Mäyränpää; Tiina A Salminen; Juhani Knuuti; Sirpa Jalkanen; Antti Saraste; Anne Roivainen

Vascular adhesion protein-1-targeted PET imaging in autoimmune myocarditis

Arghavan Jahandideh, Jenni Virta, Xiang-Guo Li, Heidi Liljenbäck, Olli Moisio, Jesse Ponkamo, Noora Rajala, Marion Alix, Jukka Lehtonen, Mikko I Mäyränpää, Tiina A Salminen, Juhani Knuuti, Sirpa Jalkanen, Antti Saraste, Anne Roivainen

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Abstract

BACKGROUND: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule and primary amine oxidase, and Gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetra-acetic acid conjugated sialic acid-binding immunoglobulin-like lectin 9 motif containing peptide ([ 68Ga]Ga-DOTA-Siglec-9) is a positron emission tomography (PET) tracer targeting VAP-1. We evaluated the feasibility of PET imaging with [ 68Ga]Ga-DOTA-Siglec-9 for the detection of myocardial lesions in rats with autoimmune myocarditis.

METHODS: Rats (n = 9) were immunized twice with porcine cardiac myosin in complete Freund's adjuvant. Control rats (n = 6) were injected with Freund's adjuvant alone. On day 21, in vivo PET/computed tomography (CT) imaging with [ 68Ga]Ga-DOTA-Siglec-9 was performed, followed by ex vivo autoradiography, histology, and immunohistochemistry of tissue sections. In addition, myocardial samples from three patients with cardiac sarcoidosis were studied.

RESULTS: [ 68Ga]Ga-DOTA-Siglec-9 PET/CT images of immunized rats showed higher uptake in myocardial lesions than in myocardium outside lesions (SUV mean, 0.5 ± 0.1 vs 0.3 ± 0.1; P = .003) or control rats (SUV mean, 0.2 ± 0.03; P < .0001), which was confirmed by ex vivo autoradiography of tissue sections. Immunohistochemistry showed VAP-1-positive staining in lesions of rats with myocarditis and in patients with cardiac sarcoidosis.

CONCLUSION: VAP-1-targeted [ 68Ga]Ga-DOTA-Siglec-9 PET is a potential novel technique for the detection of myocardial lesions.

Original language	English
Pages (from-to)	2760-2772
Number of pages	13
Journal	Journal of Nuclear Cardiology
Volume	30
Issue number	6
Early online date	27 Sept 2023
Publication status	Published - Dec 2023
MoE publication type	A1 Journal article-refereed

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https://urn.fi/URN:NBN:fi-fe20231102142330

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Jahandideh, A., Virta, J., Li, X.-G., Liljenbäck, H., Moisio, O., Ponkamo, J., Rajala, N., Alix, M., Lehtonen, J., Mäyränpää, M. I., Salminen, T. A., Knuuti, J., Jalkanen, S., Saraste, A., & Roivainen, A. (2023). Vascular adhesion protein-1-targeted PET imaging in autoimmune myocarditis. Journal of Nuclear Cardiology, 30(6), 2760-2772. https://urn.fi/URN:NBN:fi-fe20231102142330

@article{e4dee52df0ba4d458a434c64e5105bd2,

title = "Vascular adhesion protein-1-targeted PET imaging in autoimmune myocarditis",

abstract = "BACKGROUND: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule and primary amine oxidase, and Gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetra-acetic acid conjugated sialic acid-binding immunoglobulin-like lectin 9 motif containing peptide ([ 68Ga]Ga-DOTA-Siglec-9) is a positron emission tomography (PET) tracer targeting VAP-1. We evaluated the feasibility of PET imaging with [ 68Ga]Ga-DOTA-Siglec-9 for the detection of myocardial lesions in rats with autoimmune myocarditis. METHODS: Rats (n = 9) were immunized twice with porcine cardiac myosin in complete Freund's adjuvant. Control rats (n = 6) were injected with Freund's adjuvant alone. On day 21, in vivo PET/computed tomography (CT) imaging with [ 68Ga]Ga-DOTA-Siglec-9 was performed, followed by ex vivo autoradiography, histology, and immunohistochemistry of tissue sections. In addition, myocardial samples from three patients with cardiac sarcoidosis were studied. RESULTS: [ 68Ga]Ga-DOTA-Siglec-9 PET/CT images of immunized rats showed higher uptake in myocardial lesions than in myocardium outside lesions (SUV mean, 0.5 ± 0.1 vs 0.3 ± 0.1; P = .003) or control rats (SUV mean, 0.2 ± 0.03; P < .0001), which was confirmed by ex vivo autoradiography of tissue sections. Immunohistochemistry showed VAP-1-positive staining in lesions of rats with myocarditis and in patients with cardiac sarcoidosis. CONCLUSION: VAP-1-targeted [ 68Ga]Ga-DOTA-Siglec-9 PET is a potential novel technique for the detection of myocardial lesions. ",

author = "Arghavan Jahandideh and Jenni Virta and Xiang-Guo Li and Heidi Liljenb{\"a}ck and Olli Moisio and Jesse Ponkamo and Noora Rajala and Marion Alix and Jukka Lehtonen and M{\"a}yr{\"a}np{\"a}{\"a}, {Mikko I} and Salminen, {Tiina A} and Juhani Knuuti and Sirpa Jalkanen and Antti Saraste and Anne Roivainen",

note = "{\textcopyright} 2023. The Author(s).",

year = "2023",

month = dec,

language = "English",

volume = "30",

pages = "2760--2772",

journal = "Journal of Nuclear Cardiology",

issn = "1071-3581",

publisher = "Springer",

number = "6",

}

Jahandideh, A, Virta, J, Li, X-G, Liljenbäck, H, Moisio, O, Ponkamo, J, Rajala, N, Alix, M, Lehtonen, J, Mäyränpää, MI, Salminen, TA, Knuuti, J, Jalkanen, S, Saraste, A & Roivainen, A 2023, 'Vascular adhesion protein-1-targeted PET imaging in autoimmune myocarditis', Journal of Nuclear Cardiology, vol. 30, no. 6, pp. 2760-2772. <https://urn.fi/URN:NBN:fi-fe20231102142330>

TY - JOUR

T1 - Vascular adhesion protein-1-targeted PET imaging in autoimmune myocarditis

AU - Jahandideh, Arghavan

AU - Virta, Jenni

AU - Li, Xiang-Guo

AU - Liljenbäck, Heidi

AU - Moisio, Olli

AU - Ponkamo, Jesse

AU - Rajala, Noora

AU - Alix, Marion

AU - Lehtonen, Jukka

AU - Mäyränpää, Mikko I

AU - Salminen, Tiina A

AU - Knuuti, Juhani

AU - Jalkanen, Sirpa

AU - Saraste, Antti

AU - Roivainen, Anne

PY - 2023/12

Y1 - 2023/12

N2 - BACKGROUND: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule and primary amine oxidase, and Gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetra-acetic acid conjugated sialic acid-binding immunoglobulin-like lectin 9 motif containing peptide ([ 68Ga]Ga-DOTA-Siglec-9) is a positron emission tomography (PET) tracer targeting VAP-1. We evaluated the feasibility of PET imaging with [ 68Ga]Ga-DOTA-Siglec-9 for the detection of myocardial lesions in rats with autoimmune myocarditis. METHODS: Rats (n = 9) were immunized twice with porcine cardiac myosin in complete Freund's adjuvant. Control rats (n = 6) were injected with Freund's adjuvant alone. On day 21, in vivo PET/computed tomography (CT) imaging with [ 68Ga]Ga-DOTA-Siglec-9 was performed, followed by ex vivo autoradiography, histology, and immunohistochemistry of tissue sections. In addition, myocardial samples from three patients with cardiac sarcoidosis were studied. RESULTS: [ 68Ga]Ga-DOTA-Siglec-9 PET/CT images of immunized rats showed higher uptake in myocardial lesions than in myocardium outside lesions (SUV mean, 0.5 ± 0.1 vs 0.3 ± 0.1; P = .003) or control rats (SUV mean, 0.2 ± 0.03; P < .0001), which was confirmed by ex vivo autoradiography of tissue sections. Immunohistochemistry showed VAP-1-positive staining in lesions of rats with myocarditis and in patients with cardiac sarcoidosis. CONCLUSION: VAP-1-targeted [ 68Ga]Ga-DOTA-Siglec-9 PET is a potential novel technique for the detection of myocardial lesions.

AB - BACKGROUND: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule and primary amine oxidase, and Gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetra-acetic acid conjugated sialic acid-binding immunoglobulin-like lectin 9 motif containing peptide ([ 68Ga]Ga-DOTA-Siglec-9) is a positron emission tomography (PET) tracer targeting VAP-1. We evaluated the feasibility of PET imaging with [ 68Ga]Ga-DOTA-Siglec-9 for the detection of myocardial lesions in rats with autoimmune myocarditis. METHODS: Rats (n = 9) were immunized twice with porcine cardiac myosin in complete Freund's adjuvant. Control rats (n = 6) were injected with Freund's adjuvant alone. On day 21, in vivo PET/computed tomography (CT) imaging with [ 68Ga]Ga-DOTA-Siglec-9 was performed, followed by ex vivo autoradiography, histology, and immunohistochemistry of tissue sections. In addition, myocardial samples from three patients with cardiac sarcoidosis were studied. RESULTS: [ 68Ga]Ga-DOTA-Siglec-9 PET/CT images of immunized rats showed higher uptake in myocardial lesions than in myocardium outside lesions (SUV mean, 0.5 ± 0.1 vs 0.3 ± 0.1; P = .003) or control rats (SUV mean, 0.2 ± 0.03; P < .0001), which was confirmed by ex vivo autoradiography of tissue sections. Immunohistochemistry showed VAP-1-positive staining in lesions of rats with myocarditis and in patients with cardiac sarcoidosis. CONCLUSION: VAP-1-targeted [ 68Ga]Ga-DOTA-Siglec-9 PET is a potential novel technique for the detection of myocardial lesions.

M3 - Article

C2 - 37758963

SN - 1071-3581

VL - 30

SP - 2760

EP - 2772

JO - Journal of Nuclear Cardiology

JF - Journal of Nuclear Cardiology

IS - 6

ER -

Vascular adhesion protein-1-targeted PET imaging in autoimmune myocarditis

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