Effect of different cooking methods on the content and bioaccessibility of iodine components in abalone (Haliotis discus hannai).

The present study aimed to evaluate the changes in total iodine and iodine species (iodide, iodate, 3-iodo-l-tyrosine, and 3,5-diiodo-l-tyrosine) content in abalone after different treatments (raw, semi-drying, steaming, grilling, and boiling) and in-vitro digestion using high-performance liquid chromatography-inductively coupled plasma-mass spectroscopy (HPLC-ICP-MS). The highest reduction in iodine content was found in boiled abalone (64.95%), followed by steamed (32.40%) and grilled (32.11%) abalones. There is no significant difference between iodine content of raw and semi-dried abalone. Absorption efficiency was determined by an in vitro digestion procedure using simulated gastro/intestinal solutions. Unlike total iodine content after cooking, absorption efficiency increased after cooking. Absorption efficiency of semi-dried abalone is the highest (28.53%), followed by boiled (23.85%), grilled (22.62%), steamed (21.51%), and raw (12.20%) abalones. Iodide was the major form of iodine present in the abalone after cooking and in vitro digestion. No iodate was observed, and the organic iodine content was very low.

123I-2-iodo-tyrosine, a new tumour imaging agent: human biodistribution, dosimetry and initial clinical evaluation in glioma patients.

PURPOSE: 123I-2-iodo-tyrosine (123I-2IT) has been identified as a promising new amino acid tracer in animals. Uptake is mediated by LAT1 transport, which is increased in tumour cells. In this study we present the human biodistribution and first clinical results in glioma patients. METHODS: For the biodistribution study, six male volunteers received 60-95 MBq 123I-2IT. Whole-body scans and blood and urine samples were obtained up to 24 h after injection; dosimetry was calculated using OLINDA 1.0 software. Initial clinical evaluation of 123I-2IT SPECT was performed in 35 patients with suspected or known glioma, either as primary diagnosis or for detection of recurrence. Tumour-to-background (T/B) ratios were calculated for semi-quantitative analysis. The results were correlated with clinical and MRI follow-up data or histology. RESULTS: 123I-2IT showed both renal and intestinal clearance. Bladder (0.12 mGy/MBq) and small intestine (0.03 mGy/MBq) received the highest absorbed doses. The effective dose equivalent and effective dose were estimated at 0.020 and 0.016 mSv/MBq, respectively. In patients, 123I-2IT SPECT did not differentiate between neoplastic and non-neoplastic lesions after an indeterminate MRI. In follow-up of known glioma, 13/15 patients with disease recurrence had increased T/B values (range 1.39-3.91). Out of seven recurrence-negative patients, two showed an important increase in T/B, in one case due to radionecrosis (T/B 1.59) and in the other probably due to residual but stable disease (T/B 2.07). CONCLUSION: 123I-2IT has a favourable biodistribution for a tumour imaging agent. It shows increased uptake in central nervous system glioma and is potentially useful in the follow-up of glioma patients.

Comparison of the uptake of [123/125I]-2-iodo-D-tyrosine and [123/125I]-2-iodo-L-tyrosine in R1M rhabdomyosarcoma cells in vitro and in R1M tumor-bearing Wag/Rij rats in vivo.

INTRODUCTION: Recently, promising results concerning uptake in vivo in tumors of D-amino acids have been published. Therefore, we decided to evaluate the tumor uptake of the D-analogue of [(123)I]-2-iodo-L-tyrosine, a tracer recently introduced by our group into clinical trials. The uptake of 2-amino-3-(4-hydroxy-2-[(123/125)I]iodophenyl)-D-propanoic acid (2-iodo-D-tyrosine) was studied in vitro in LAT1-expressing R1M rat rhabdomyosarcoma cells and in vivo in R1M tumor-bearing Wag/Rij rats. METHODS: The uptake of [(125)I]-2-iodo-L-tyrosine and [(125)I]-2-iodo-D-tyrosine into R1M cells was determined in appropriate buffers, allowing the study of the involved transport systems. In vivo, the biodistribution in R1M-bearing rats of [(123)I]-2-iodo-L-tyrosine and [(123)I]-2-iodo-D-tyrosine was performed by both dynamic and static planar imaging with a gamma camera. RESULTS: In in vitro conditions, the uptake of both [(125)I]-2-iodo-L-tyrosine and [(125)I]-2-iodo-D-tyrosine in the HEPES buffer was 25% higher in the presence of Na(+) ions. In the absence of Na(+) ions, [(125)I]-2-iodo-D-tyrosine was taken up reversibly in the R1M cells, with an apparent accumulation, probably for the larger part by the LAT1 system. Dynamic planar imaging showed that the uptake in the tumors of [(123)I]-2-iodo-D-tyrosine was somewhat lower than that of [(123)I]-2-iodo-L-tyrosine. At 30 min postinjection, the mean differential uptake ratio values of the L- and D-enantiomers are 2.5+/-0.7 and 1.7+/-0.6, respectively. Although the uptake of the D-isomer is lower, probably due to a faster clearance from the blood, the tumor-background ratio is the same as that of the l-analogue. CONCLUSION: A large part (75%) of [(125)I]-2-iodo-D-tyrosine in vitro and [(123)I]-2-iodo-D-tyrosine in vivo is reversibly highly taken up in R1M tumor cells by Na(+)-independent LAT transport systems, more likely by the LAT1. The clearance from the blood of [(123)I]-2-iodo-D-tyrosine in the rats is faster than that of the L-analogue, resulting in a slightly lower tumor uptake but with the same tumor-background ratio.

Comparative biodistribution study of the new tumor tracer [123I]-2-iodo-L-phenylalanine with [123I]-2-iodo-L-tyrosine.

INTRODUCTION: Both A- and l-type amino acid transport are increased in tumor cells relative to normal tissue; these transport systems have been the major focus of the development of amino acid tumor tracers to overcome the limitations of [(18)F]-fluorodeoxyglucose ((18)F-FDG). The newly developed tracer 2-amino-3-(2-[(123)I]iodophenyl)propanoic acid ([(123)I]-2-iodo-l-phenylalanine) showed high and specific tumor uptake, slow renal elimination and low brain uptake. We compared [(123)I]-2-iodo-L-phenylalanine with 2-amino-3-(4-hydroxy-2-[(123)I]iodophenyl)propanoic acid ([(123)I]-2-iodo-L-tyrosine), an L-tyrosine analogue that has recently entered clinical trials. METHODS: [(123)I]-2-iodo-L-phenylalanine and [(123)I]-2-iodo-L-tyrosine were evaluated in rhabdomyosarcoma tumor-bearing athymic mice by means of dynamic planar imaging (DPI) and dissection. A displacement study with L-phenylalanine was performed to prove the specificity of tracer tumor uptake, and kinetic modeling was applied to the DPI results. Moreover, the biodistribution of both tracers was compared with that of (18)F-FDG. RESULTS: Both [(123)I]-2-iodo-L-phenylalanine and [(123)I]-2-iodo-L-tyrosine showed fast, high and specific tumor accumulation with no significant difference. However, [(123)I]-2-iodo-L-phenylalanine was cleared faster from the blood to the bladder in comparison with the tyrosine analogue. Moreover, [(123)I]-2-iodo-L-phenylalanine tumor uptake equilibrated faster with blood. Dissection showed that [(123)I]-2-iodo-L-tyrosine slightly accumulated in the liver, which was not the case for the phenylalanine analogue. In contrast to (18)F-FDG, both tracers showed low uptake in the heart and normal brain tissue, which is advantageous for tumor detection in these organs. CONCLUSIONS: [(123)I]-2-iodo-L-phenylalanine showed more promising characteristics for oncological imaging as compared with [(123)I]-2-iodo-L-tyrosine. The former tracer not only demonstrated faster blood clearance but also showed that the tracer uptake in the tumor reached its equilibrium with the blood pool activity faster, which led to faster and better tumor contrast. Moreover, both tracers could overcome an important limitation of (18)F-FDG-its high normal brain uptake.

SPECT and PET amino acid tracer influx via system L (h4F2hc-hLAT1) and its transstimulation.

UNLABELLED: System L amino acid transport is increased in various types of cancer. The tracer 123I-2-iodotyrosine (2IT), which is accumulated via system L, could thus serve to allow visualization of cancer in vivo. Here, we studied the transport of 125I-2IT by h4F2hc-hLAT1, the major transporter subserving system L in growing cells, using the Xenopus laevis oocyte expression system. We compared the apparent affinity of 125I-2IT with that of tyrosine, tested the influence of intracellular methionine availability on the influx rate of this substrate, and then compared the transport of 2IT with that of the other tracers-iodo-alpha-methyltyrosine (IMT), fluoroethyltyrosine (FET), and 2-fluorotyrosine (2FT)-by measuring their transstimulating effect on phenylalanine efflux. METHODS: Transport experiments were performed with Xenopus laevis oocytes expressing h4F2hc-hLAT1 (the functional transporter) and oocytes expressing only h4F2hc (negative control). The values obtained for the functional transporter were corrected for endogenous background transport by subtracting the values for the negative controls. RESULTS: The apparent affinity for 125I-2IT and 3H-tyrosine was 29.3 +/- 9.3 micromol/L and 21.2 +/- 4.2 micromol/L, respectively. The influx rate of 125I-2IT was, similarly to that of 3H-phenylalanine, transstimulated by a factor of > or =3 when the oocytes were preinjected with methionine or phenylalanine. The proportion of preinjected 3H-phenylalanine that effluxed within 90 s in the presence of an extracellular 2IT concentration of 0.1 mmol/L was 4.1% +/- 0.5%, compared with 3.3% +/- 0.4% for extracellular IMT, 1.3% +/- 0.3% for FET, 9.3% +/- 0.8% for 2FT, and 9.1% +/- 0.5% for phenylalanine. CONCLUSION: 2IT has a high affinity for h4F2hc-hLAT1, comparable to that of natural tyrosine, and its influx rate is transstimulated by intracellular amino acids. The 2IT influx rate is comparable to that of IMT but lower than that of phenylalanine. In contrast to FET, which is only poorly transported, 2FT displays a high influx rate equal to that of phenylalanine.

In vitro characterization of the influx of 3-[125I]iodo-L-alpha-methyltyrosine and 2-[125I]iodo-L-tyrosine into U266 human myeloma cells: evidence for system T transport.

The aim of this study was to investigate the cellular uptake mechanisms responsible for the accumulation of 3-[(125)I]iodo-L-alpha-methyltyrosine ((125)I-3-IMT) and 2-[(125)I]iodo-L-tyrosine ((125)I-2-IT), two radiotracers for metabolic tumor imaging, using single-photon emission tomography, into U266 human myeloma cancer cells. Time course and concentration dependency of (125)I-3-IMT uptake was assessed. Kinetic parameters were calculated using an Eadie Hofstee plot. A set of competitive inhibitors of the main amino acid transport systems was used for the discrimination of the transporters responsible for the uptake of (125)I-3-IMT and (125)I-2-IT. Protein incorporation of both tracers was determined using acid precipitation. The measured maximum velocity for (125)I-3-IMT transport was 4.199 nmol per mg protein 20 s(-1), and the Michaelis constant was 107.9 microM. Addition of 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH), a competitive inhibitor of System L, reduced the influx by 39.0+/-3.3% for (125)I-3-IMT and 66.3+/-0.9% for (125)I-2-IT. The BCH-insensitive influx was further reduced by Tryptophan (Trp) by 43.8+/-3.5% for (125)I-3-IMT and 15.3+/-1.3% for (125)I-2-IT. This suggests involvement of System T transport. We measured <2% of radioactivity in the acid precipitable fractions of both tracers with no increase in time. We conclude that the influx of (125)I-3-IMT and (125)I-2-IT into U266 human myeloma cells is mediated by both System L and System T amino acid transporters. The kinetic parameters suggest that elevated plasma levels of aromatic amino acids will reduce (123)I-3-IMT uptake in myeloma patients. Both tracers do not enter protein synthesis significantly.

Brain uptake of iodinated L-meta-tyrosine, a metabolically stable amino acid derivative.

The possibility of using L-meta-tyrosine (L-mTyr) with high metabolic stability and amino acid transport affinity was evaluated. mTyr was first separated into D- and L-isomers with high-performance liquid chromatography and both were labelled with non-carrier-mediated 125I. Biodistribution and pharmacological studies of radioiodinated mTyr in mice and rats were then performed. 125I-L-mTyr showed greater accumulation in the brain and the pancreas. It accumulated in the brain stereospecifically in the in vivo studies and by the L-tyrosine competitive energy dependent transport system in the in vitro studies. It was resistant to deiodination, appeared to have no retention mechanism and was rapidly excreted. 123I-L-mTyr has the potential of an amino acid transport marker, especially in the brain and the pancreas.

Monoiodo-D-tyrosine, an artificial amino acid radiopharmaceutical for selective measurement of membrane amino acid transport in the pancreas.

Using 11C-labeled natural amino acids, the functional diagnosis of tissue metabolism has been actively studied. Our interest has been focused on developing a clinically available 123I-labeled artificial amino acid with a single metabolic function. For this study, [123I]3-iodo-D-tyrosine ([123I]D-MIT) was selected. In vitro and in vivo studies using 125I-labeled D-MIT indicated that it showed a high pancreatic accumulation, selective affinity for membrane active transport systems, and was stable against enzymatic deiodination. A canine scintigraphic study using 123I-labeled D-MIT and kinetic analysis showed that it behaved as an "artificial amino acid" radiopharmaceutical with selective membrane amino acid transport affinity in the pancreas.