Hepatobiliary Excretion PET/CT With 68Ga-TAoS-DAZA to Evaluate Bile Duct Patency

Freesmeyer, Martin; Drescher, Robert; Kühnel, Christian; Gühne, Falk; Greiser, Julia

doi:10.1097/rlu.0000000000003719

Cited by 2 publications

(1 citation statement)

References 9 publications

(16 reference statements)

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“…Our group has designed and established the 68 Ga chelator group TAoS-DAZA as a potential hepatobiliary PET imaging agent [ 1 , 13 ]. Recently, we could show that the [ 68 Ga]Ga-TAoS-DAZA complexes are suitable for liver imaging with PET, allowing for biliary stent integrity diagnosis, potentially also for liver function quantification and differential diagnosis of liver nodules [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

The synthesis of N ,1,4-tri(alkoxy-hydroxybenzyl)-1,4-diazepane-amines: investigations on reaction characteristics and mechanism

Zenner,

Steinmetzer,

Ueberschaar

et al. 2024

R. Soc. Open Sci.

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1,4-Diazepane-6-amine (DAZA) can be alkylated with three 2-hydroxybenzyl pendant arms, resulting in hexadentate chelators suitable for coordination of radiometals like 68 Ga. These chelators, N ,1,4-tri(alkoxy-2-hydroxybenzyl)-DAZA, can be produced via a one-pot synthesis, with the first step being a carbonyl amine condensation of DAZA with two respective 4-alkoxy-2-hydroxybenzaldehydes, followed by reductive amination with sodium borohydride. While the first step of this reaction is predictable, the subsequent reductive amination can result in either mono-, di- or tri(alkoxy-hydroxybenzyl)-DAZA compounds. Seeking to identify dependencies that might allow a specific reaction control towards the formation of either of the three possible products, and particularly towards the favoured trialkylated DAZA compounds, a variety of synthesis trials were performed. Additionally, computational methods were employed to evaluate the underlying reaction mechanism. Synthesis trials verified that the trialkylated DAZA compounds are formed via direct reductive amination of the dialkylated DAZA compounds. Subsequently, a synthetic method was established, leading to an increase in the percentage of the trialkylated DAZA compounds, which allowed the successful isolation of those hexadentate chelators. Additionally, an alternative pathway proceeding via aminal C–N bond insertion of an attacking third carbonyl moiety was evaluated by means of quantum chemical calculations but so far remains entirely hypothetical.

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Section: Introductionmentioning

confidence: 99%

The synthesis of N ,1,4-tri(alkoxy-hydroxybenzyl)-1,4-diazepane-amines: investigations on reaction characteristics and mechanism

Zenner,

Steinmetzer,

Ueberschaar

et al. 2024

R. Soc. Open Sci.

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Automated GMP Production and Preclinical Evaluation of [68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA

et al. 2022

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[68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA are two novel radiotracers suitable for functional PET liver imaging. Due to their specific liver uptake and biliary excretion, the tracers may be applied for segmental liver function quantification, gall tree imaging and the differential diagnosis of liver nodules. The purpose of this study was to investigate problems that occurred initially during the development of the GMP compliant synthesis procedure and to evaluate the tracers in a preclinical model. After low radiolabeling yields were attributed to precursor instability at high temperatures, an optimized radiolabeling procedure was established. Quality controls were in accordance with Ph. Eur. requirements and gave compliant results, although the method for the determination of the 68Ga colloid is partially inhibited due to the presence of a radioactive by-product. The determination of logP revealed [68Ga]Ga-TEoS-DAZA (ethoxy bearing) to be more lipophilic than [68Ga]Ga-TMoS-DAZA (methoxy bearing). Accordingly, biodistribution studies in an in ovo model showed a higher liver uptake for [68Ga]Ga-TEoS-DAZA. In dynamic in ovo PET imaging, rapid tracer accumulation in the liver was observed. Similarly, the activity in the intestines rose steadily within the first hour p.i., indicating biliary excretion. As [68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA can be prepared according to GMP guidelines, transition into the early clinical phase is now possible.

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Hepatobiliary Excretion PET/CT With 68Ga-TAoS-DAZA to Evaluate Bile Duct Patency

Cited by 2 publications

References 9 publications

The synthesis of N ,1,4-tri(alkoxy-hydroxybenzyl)-1,4-diazepane-amines: investigations on reaction characteristics and mechanism

The synthesis of N ,1,4-tri(alkoxy-hydroxybenzyl)-1,4-diazepane-amines: investigations on reaction characteristics and mechanism

Automated GMP Production and Preclinical Evaluation of [68Ga]Ga-TEoS-DAZA and [68Ga]Ga-TMoS-DAZA

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