Basil Künnecke

Gastrointestinal transit times in mice and humans measured with 27Al and 19F nuclear magnetic resonance.

Gastric emptying and gastrointestinal (GI) transit times in mice and humans were monitored noninvasively by using 27Al and 19F nuclear magnetic resonance (NMR). Al3+ bound to ion‐exchange resin and perfluorononane were administered orally as selective and specific markers for the stomach and the entire GI tract, respectively. 27Al‐ and 19F‐MR spectroscopy (MRS) was employed to follow quantitatively boli of the mixed markers in awake, fed mice over a period of 48 hr. The selectivity of the markers was confirmed by whole‐body 1H‐, 27Al‐, and 19F‐MRI of anesthetized mice. Gastric emptying in humans was also monitored with 27Al‐MRS of aluminum‐loaded ion exchange resin. GI transit was assessed by 19F projection imaging of pharmaceutical capsules tagged with perfluorononane. Quantitative analysis of the MR data revealed that gastric emptying in humans proceeded linearly, whereas in mice an exponential decay was observed. This difference is explained by the respective feeding patterns of humans and mice. Humans usually achieve nearly complete gastric emptying before each meal. In contrast, very short delays between successive food intakes in small animals result in successive dilution of the stomach contents. For stomach emptying in mice the exponential decay constant was 74 min, whereas the half‐time of the linear gastric emptying in humans was 30 min. Magn Reson Med 48:255–261, 2002.

Glycogen metabolism as detected by in vivo and in vitro 13C-NMR spectroscopy using [1,2-13C2]glucose as substrate.

The metabolism of glucose to glycogen in the liver of fasted and well-fed rats was investigated with 13C nuclear magnetic resonance spectroscopy using [1,2-(13)C2]glucose as the main substrate. The unique spectroscopic feature of this molecule is the 13C-13C homonuclear coupling leading to characteristic doublets for the C-1 and C-2 resonances of glucose and its breakdown products as long as the two 13C nuclei remain bonded together. The doublet resonances of [1,2-(13)C2]glucose thus provide an ideal marker to follow the fate of this exogenous substrate through the metabolic pathways. [1,2-(13)C2]Glucose was injected intraperitoneally into anesthetized rats and the in vivo 13C-NMR measurements of the intact animals revealed the transformation of the injected glucose into liver glycogen. Glycogen was extracted from the liver and high resolution 13C-NMR spectra were obtained before and after hydrolysis of glycogen. Intact [1,2-13C2]glucose molecules give rise to doublet resonances, natural abundance [13C]glucose molecules produce singlet resonances. From an analysis of the doublet-to-singlet intensities the following conclusions were derived. (i) In fasted rats virtually 100% of the glycosyl units in glycogen were 13C-NMR visible. In contrast, the 13C-NMR visibility of glycogen decreased to 30-40% in well-fed rats. (ii) In fed rats a minimum of 67 +/- 7% of the exogenous [1,2-(13)C2]glucose was incorporated into the liver glycogen via the direct pathway. No contribution of the indirect pathway could be detected. (iii) In fasted rats externally supplied glucose appeared to be consumed in different metabolic processes and less [1,2-(13)C2]glucose was found to be incorporated into glycogen (13 +/- 1%). However, the observation of [5,6-(13)C2]glucose in liver glycogen provided evidence for the operation of the so-called indirect pathway of glycogen synthesis. The activity of the indirect pathway was at least 9% but not more than 30% of the direct pathway. (vi) The pentose phosphate pathway was of little significance for glucose but became detectable upon injection of [1-(13)C]ribose.

19F-MRI of perfluorononane as a novel contrast modality for gastrointestinal imaging.

19F‐Magnetic resonance imaging in conjunction with perfluorononane provides a new modality for gastrointestinal (GI) imaging as is demonstrated here with an animal model. Perfluorononane was found to be an ideal oral contrast agent since it is biologically inert, immiscible with water, and since it has a low viscosity and surface tension. Furthermore, its high fluorine content, together with the high sensitivity of 19F‐MRI, allowed highly selective MR images of the GI tract of mice to be acquired. Due to the lack of 19F background signals, the contrast of the GI tract was only limited by the signal‐to‐noise ratio of the 19F‐MR images. 19F‐RARE images of 1‐mm slices with an in‐plane resolution of 0.23 × 0.23 mm2 were obtained from the GI tract after oral perfluorononane administration. The passage of perfluorononane through the entire GI tract was monitored by repetitive MR measurements with a maximal time resolution of 38 s. The three‐dimensional surfaces of the GI tract were reconstructed and superimposed on corresponding 1H‐MR images, which provided complementary anatomical information. Magn Reson Med 41:80‐86, 1999.

In vivo and in vitro 27Al NMR studies of aluminum(III) chelates of triazacyclononane polycarboxylate ligands

The metallic radioisotope of a known radiopharmaceutical chelate, (67)Ga(NOTA) (NOTA=1,4,7-triazacyclonane-1,4,7-triacetic acid), used for tumor detection, was substituted by the chemically similar but non radioactive aluminum ion. Our aim was to detect and evaluate the in vivo behavior of the chelate. For this purpose, Al(NOTA) and the related chelate Al(NODASA) (NODASA=1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid) were studied using in vitro and in vivo (27)Al NMR spectroscopy in rats. Both chelates showed high stability towards acid catalyzed dissociation and their (27)Al NMR resonances are characteristic of highly symmetrical species, with chemical shifts within the range for octahedral or pseudo-octahedral geometries. The thermodynamic stability constant of the novel chelate Al(NODASA) was estimated using (27)Al NMR. The value obtained suggested that the chelate does not undergo in vivo demetalation by transferrin. The in vivo spectroscopic studies and the analysis of blood and urine samples for Al(III) concentrations indicated that the chelates remain intact under physiological conditions and that they are mainly eliminated from the body through the kidneys.