Abstract
Overexpression of the 18-kDa translocator protein (TSPO) is closely linked to inflammatory responses in the heart, including myocarditis, which can lead to myocardial necrosis. In vivo assessment of inflammatory responses has enabled the precise diagnosis of myocarditis to improve clinical outcomes. Here, we evaluated TSPO overexpression in a rat model of experimental autoimmune myocarditis (EAM) compared to healthy rats using two TSPO radiotracers, [18F]fluoromethyl-PBR28 ([18F]1) and [18F]CB251 ([18F]2). All radiolabeling methods were successfully applied to an automated module for the reproducible preparation of TSPO radiotracers. Both radiotracers were directly compared in an EAM rat model, as well as in healthy rats to determine whether either radiotracer provides a more promising assessment of in vivo TSPO overexpression. [18F]2 provided more specific TSPO-uptake in the heart of the EAM rats (1.32-fold that of the heart-to-lung uptake ratio versus healthy controls), while [18F]1 did not show a significant difference between the two groups. Histopathological characterization revealed that a prominent positron emission tomography (PET) signal of [18F]2 in the EAM rats corresponded to the presence of a higher density of TSPO compared to the healthy controls. These results suggest that the imidazole[1,2-a]pyridine-based radiotracer [18F]2 is a sensitive tool for noninvasively diagnosing myocarditis related to inflammation of the heart muscle by assessing abnormal TSPO expression.
Highlights
The 18-kDa translocator protein (TSPO), which is located mainly in the outer membrane of mitochondria, is a well-established biomarker of brain injury and cancer because it is excessively expressed in such lesions [1,2,3]
Unlike the reported methods, [18F]1 was prepared in two steps from dibromomethane by nucleophilic aliphatic substitution, which involved the preparation of the radioactive intermediate CH2Br[18F]F followed by O-alkylation of desmethyl-PBR28 [24]
We evaluated the feasibility of positron emission tomography (PET) imaging by using TSPO radiotracers to noninvasively assess abnormal TSPO expression in the established rat model of myocarditis
Summary
The 18-kDa translocator protein (TSPO), which is located mainly in the outer membrane of mitochondria, is a well-established biomarker of brain injury and cancer because it is excessively expressed in such lesions [1,2,3]. TSPO regulates cholesterol transport, cell proliferation, apoptosis, and inflammation [4,5]. TSPO is important in detecting inflammation in terms of macrophage. TSPO regulates cholesterol transport, cell proliferation, apop2toosf i1s0, and inflammation [4,5]. TSPO is important in detecting inflammation in terms of macrophage infiltration. Studies on TSPO are limited to specific diseases such as glioblastoma, innefiulrtroadtieogne.nSetruadtiioens,oannTdSPpOroastraetleimanitdedbtroeaspstecciafinccderise[6a–se8s].sHucohwaesvgerli,omblaanstyomstau,dnieeus roondemgeynoecraartdioianl, ainnfdlapmromstaattieona,npdabrrteicaustlacralnyctehre[6r–o8le]. [125I]IodoDPA-713, one TSPO radiotracer, has been evaluated for the ability to detect myocRaercdeinaltlyi,nf[l1a2m5Im]IoadtiooDn PiAn-7a13m, oounsee TmSoPdOelraodf iocotrxascaecrk, iehvaisrubseeBn3 e(vCaVluBa3t)edmyfoorcatrhdeitiasbi[l2it0y,21to]. SSttrruuccttuurreeoof fththee181-8k-DkDa atratrnasnloscloactoartoprroptreoitnei(nTS(PTOSP) Ora)driaodtriaocterarsce[1r8sF[]1fl8Fu]oflruoomreotmhyelt-hPyBl-RP2B8Rf2o8r [f1o8rF[]118Fa]n1dan[1d8F[]18CFB]C25B125fo1rf[o1r8F[1]82F.]2
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