Gastric emptying and gastrointestinal (GI) transit times in mice and humans were monitored noninvasively by using 27 Al and 19 F nuclear magnetic resonance (NMR). Al 3؉ bound to ion-exchange resin and perfluorononane were administered orally as selective and specific markers for the stomach and the entire GI tract, respectively.27 Al-and 19 F-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 1 H-, 27 Al-, and 19 F-MRI of anesthetized mice. Gastric emptying in humans was also monitored with 27 Al-MRS of aluminum-loaded ion exchange resin. GI transit was assessed by 19 F 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.

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.

Aluminum NMR is proposed as a new imaging and spectroscopy modality. Its potential is exemplified by in vivo studies of the human stomach. The dissolution kinetics of aluminum-containing drugs at physiological doses and their removal from the human stomach have been followed by 27Al magnetic resonance spectroscopy (MRS). Aluminum concentrations as low as 0.5 mg Al3+ in the human stomach can be detected. The time course of gastric emptying has been visualized with 27Al magnetic resonance imaging (MRI) under normal conditions and in the presence of an antimuscarinic agent, which reduces the gastric motor function. 27Al MRI is the only direct method to visualize the gastric pH. 27Al MRI opens new possibilities for medical and pharmaceutical science.

This study describes for the first time results of a (19)F-MRS study on humans exposed to the fluorinated non-steroidal anti-inflammatory drug niflumic acid. The accumulation and elimination of this commercially available selective prostaglandin synthase inhibitor is studied after an oral bolus in the human liver, in blood plasma and in urine samples. The in vivo spectra of the liver display two resonances with a similar increase in signal intensity during the investigation period of 240 min. One resonance refers to the parent compound niflumic acid (P), whereas the second resonance corresponds to a metabolite (M1) formed by the biotransformation by liver enzymes. The spectroscopic comparison with model compounds suggests 4'-hydroxyniflumic acid as the metabolite. During the entire experiment the concentration ratios of these resonances (P/M1) ranged between 0.7 and 0.9, indicating a high metabolite concentration most probably due to an efficient first pass metabolism. Both resonances (P, M1) were observed in the in vitro study of the blood plasma samples after plasma protein denaturation. However, in comparison to the liver spectra, the amount of the metabolite M1 is very small with a P/M1-ratio of 36.6 after 90 min and 16.1 after the end of measurement. This finding suggests an efficient biliary excretion of the metabolite M1, which bypasses the blood circulation system. Both resonances are also identified in the native urine samples. The signal intensity of the parent compound dominates the spectra of all urine samples, whereas the signal intensity of M1 increases slowly reaching a similar value to the parent compound P at the end of the measurement. This observation demonstrates an effective renal elimination of niflumic acid and suggests the existence of an enterohepatic circuit with a re-entry mechanism for the biliary excreted metabolite M1. In the urine spectra, an additional metabolite M2 is found. This resonance exhibits a low but constant signal intensity. The chemical origin of this metabolite is unclear.

Silicon-29 (29Si) imaging was investigated as a potential imaging modality for monitoring silicone prostheses in humans. The 29Si relaxation times of several silicone gels were measured and found to average T1 = 21.2 +/- 1.5 s and T2 = 207 +/- 40 ms, with no significant difference between virgin and explanted gels. A single-shot half-Fourier rapid acquisition with relaxation enhancement (RARE) and a refocused gradient-echo sequence were used for acquiring 29Si images with 5 x 5 mm2 resolution and no slice selection. Three volunteers with silicone-gel-filled breast implants and one subject with an intraocular silicone oil injection were thus examined in a total acquisition time of 10-15 min per image. On all 29Si images, the shape of the silicone object was well depicted. Although at present, conventional proton images are superior in resolution and signal-to-noise ratio, 29Si imaging has the advantage of optimal specificity, since only the silicone itself is visible.