Dataset Information

Preparation and in vivo characterization of ⁵¹MnCl₂ as PET tracer of Ca²⁺ channel-mediated transport.

ABSTRACT: Manganese has long been employed as a T₁-shortening agent in magnetic resonance imaging (MRI) applications, but these techniques are limited by the biotoxicity of bulk-manganese. Positron emission tomography (PET) offers superior contrast sensitivity compared with MRI, and recent preclinical PET studies employing ^52gMn (t_1/2: 5.6 d, ?⁺: 29%) show promise for a variety of applications including cell tracking, neural tract tracing, immunoPET, and functional ?-cell mass quantification. The half-life and confounding gamma emissions of ^52gMn are prohibitive to clinical translation, but the short-lived ⁵¹Mn (t_1/2: 46?min, ?⁺: 97%) represents a viable alternative. This work develops methods to produce ⁵¹Mn on low-energy medical cyclotrons, characterizes the in vivo behavior of ⁵¹MnCl₂ in mice, and performs preliminary human dosimetry predictions. ⁵¹Mn was produced by proton irradiation of electrodeposited isotopically-enriched ⁵⁴Fe targets. Radiochemically isolated ⁵¹MnCl₂ was intravenously administered to ICR mice which were scanned by dynamic and static PET, followed by ex vivo gamma counting. Rapid blood clearance was observed with stable uptake in the pancreas, kidneys, liver, heart, and salivary gland. Dosimetry calculations predict that 370?MBq of ⁵¹Mn in an adult human male would yield an effective dose equivalent of approximately 13.5?mSv, roughly equivalent to a clinical [¹⁸F]-FDG procedure.

SUBMITTER: Graves SA

PROVIDER: S-EPMC5465055 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Preparation and in vivo characterization of 51MnCl2 as PET tracer of Ca2+ channel-mediated transport.

Graves Stephen A SA Hernandez Reinier R Valdovinos Hector F HF Ellison Paul A PA Engle Jonathan W JW Barnhart Todd E TE Cai Weibo W Nickles Robert J RJ

Scientific reports 20170608 1

Manganese has long been employed as a T1-shortening agent in magnetic resonance imaging (MRI) applications, but these techniques are limited by the biotoxicity of bulk-manganese. Positron emission tomography (PET) offers superior contrast sensitivity compared with MRI, and recent preclinical PET studies employing 52gMn (t1/2: 5.6 d, β+: 29%) show promise for a variety of applications including cell tracking, neural tract tracing, immunoPET, and functio ...[more]

PMID: 28596540

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Project description:Mammalian circadian (24 h) rhythms are timed by the pattern of spontaneous action potential firing in the suprachiasmatic nucleus (SCN). This oscillation in firing is produced through circadian regulation of several membrane currents, including large-conductance Ca2+- and voltage-activated K+ (BK) and L-type Ca2+ channel (LTCC) currents. During the day steady-state BK currents depend mostly on LTCCs for activation, whereas at night they depend predominantly on ryanodine receptors (RyRs). However, the contribution of these Ca2+ channels to BK channel activation during action potential firing has not been thoroughly investigated. In this study, we used a pharmacological approach to determine that both LTCCs and RyRs contribute to the baseline membrane potential of SCN action potential waveforms, as well as action potential-evoked BK current, during the day and night, respectively. Since the baseline membrane potential is a major determinant of circadian firing rate, we focused on the LTCCs contributing to low voltage activation of BK channels during the subthreshold phase. For these experiments, two LTCC subtypes found in SCN (CaV1.2 and CaV1.3) were coexpressed with BK channels in heterologous cells, where their differential contributions could be separately measured. CaV1.3 channels produced currents that were shifted to more hyperpolarized potentials compared with CaV1.2, resulting in increased subthreshold Ca2+ and BK currents during an action potential command. These results show that although multiple Ca2+ sources in SCN can contribute to the activation of BK current during an action potential, specific BK-CaV1.3 partnerships may optimize the subthreshold BK current activation that is critical for firing rate regulation.NEW & NOTEWORTHY BK K+ channels are important regulators of firing. Although Ca2+ channels are required for their activation in excitable cells, it is not well understood how BK channels activate using these Ca2+ sources during an action potential. This study demonstrates the differences in BK current activated by CaV1.2 and CaV1.3 channels in clock neurons and heterologous cells. The results define how specific ion channel partnerships can be engaged during distinct phases of the action potential.

Dataset Information

Preparation and in vivo characterization of ⁵¹MnCl₂ as PET tracer of Ca²⁺ channel-mediated transport.

Publications

Preparation and in vivo characterization of <sup>51</sup>MnCl<sub>2</sub> as PET tracer of Ca<sup>2+</sup> channel-mediated transport.

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