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Evaluation of [⁶⁸Ga]Ga-NODAGA-RGD for PET Imaging of Rat Autoimmune Myocarditis.

ABSTRACT: The ⁶⁸Gallium-labeled 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid conjugated radiolabelled arginine-glycine-aspartic acid peptide ([⁶⁸Ga]Ga-NODAGA-RGD) is a positron emission tomography (PET) tracer binding to cell surface receptor α_vβ₃ integrin that is upregulated during angiogenesis and inflammation. We studied whether α_vβ₃ targeting PET imaging can detect myocardial inflammation in a rat model of autoimmune myocarditis. To induce myocarditis, rats (n = 8) were immunized with porcine cardiac myosin in complete Freund's adjuvant on days 0 and 7. Control rats (n = 8) received Freund's adjuvant alone. On day 21, in vivo PET/CT imaging with [⁶⁸Ga]Ga-NODAGA-RGD followed by ex vivo autoradiography and immunohistochemistry were carried out. Inflammatory lesions were detected histologically in the myocardium of 7 out of 8 immunized rats. In vivo PET images showed higher [⁶⁸Ga]Ga-NODAGA-RGD accumulation in the myocardium of rats with inflammation than the non-inflamed myocardium of control rats (SUV_mean 0.4 ± 0.1 vs. 0.1 ± 0.02; P = 0.00006). Ex vivo autoradiography and histology confirmed that [⁶⁸Ga]Ga-NODAGA-RGD uptake co-localized with inflammatory lesions containing α_vβ₃ integrin-positive capillary-like structures. A non-specific [⁶⁸Ga]Ga-DOTA-(RGE)₂ tracer showed 76% lower uptake than [⁶⁸Ga]Ga-NODAGA-RGD in the inflamed myocardium. Our results indicate that α_vβ₃ integrin-targeting [⁶⁸Ga]Ga-NODAGA-RGD is a potential PET tracer for the specific detection of active inflammatory lesions in autoimmune myocarditis.

SUBMITTER: Jahandideh A

PROVIDER: S-EPMC8714834 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:68Ga-NODAGA-exendin-4 is a promising tracer for β-cell imaging using PET/CT. Possible applications include preoperative visualization of insulinomas and discrimination between focal and diffuse forms of congenital hyperinsulinism. There is also a significant role for this tracer in extending our knowledge on the role of β-cell mass in the pathophysiology of type 1 and type 2 diabetes by enabling noninvasive quantification of tracer uptake as a measure for β-cell mass. Calculating radiation doses from this tracer is important to assess its safety for use in patients (including young children) with benign diseases and healthy individuals. Methods: Six patients with hyperinsulinemic hypoglycemia were included. After intravenous injection of 100 MBq of the tracer, 4 successive PET/CT scans were obtained at 30, 60, 120, and 240 min after injection. Tracer activity in the pancreas, kidneys, duodenum, and remainder of the body were determined, and time-integrated activity coefficients for the measured organs were calculated. OLINDA/EXM software, version 1.1, was applied to calculate radiation doses using the reference adult male and female models and to estimate radiation doses to children. Results: The mean total effective dose for adults was very low (0.71 ± 0.07 mSv for a standard injected dose of 100 MBq). The organ with the highest absorbed dose was the kidney (47.3 ± 10.2 mGy/100 MBq). The estimated effective dose was 2.32 ± 0.32 mSv for an injected dose of 20 MBq in newborns. This dose decreased to 0.77 ± 0.11 mSv/20 MBq for 1-y-old children and 0.59 ± 0.05 mSv for an injected dose of 30 MBq in 5-y-old children. Conclusion: Our human PET/CT-based dosimetric calculations show that the effective radiation doses from the novel tracer 68Ga-NODAGA-exendin-4 are very low for adults and children. The doses are lower than reported for other polypeptide tracers such as somatostatin analogs (2.1-2.6 mSv/100 MBq) and are beneficial for application as a research tool, especially when repeated examinations are needed.

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Evaluation of [⁶⁸Ga]Ga-NODAGA-RGD for PET Imaging of Rat Autoimmune Myocarditis.

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Dataset Information

Evaluation of [68Ga]Ga-NODAGA-RGD for PET Imaging of Rat Autoimmune Myocarditis.

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OmicsDI is part of the ELIXIR infrastructure

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Evaluation of [⁶⁸Ga]Ga-NODAGA-RGD for PET Imaging of Rat Autoimmune Myocarditis.