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At least 19 recordsLinked to original sources

Chemical and thermodynamic characteristics of the isotopic exchange reaction between radioiodine and iodohippuric acid isomers.

The parameters affecting the absolute radiochemical yield of the isotopic exchange reaction between radioiodine (125I-) and iodohippuric acid isomers on molten ammonium acetate as a medium exchange at 120 degrees C without any carrier added (radioiodine, 125I-) was determined. The isotopic exchange reactions of radioiodine as 125I- for iodine-127 of o- and p-iodohippuric acid isomers occur more rapidly than m-iodohippuric acid isomer. These reactions proceed by nucleophilic second order substitution reaction. The kinetics and thermodynamic parameters of these isotopic exchange reactions were determined. The absolute radiochemical yield and radio pharmaceutical purity were determined by HPLC and TLC techniques.

Journal Article↗

A novel radioiodination reagent for protein radiopharmaceuticals with L-lysine as a plasma-stable metabolizable linkage to liberate m-iodohippuric acid after lysosomal proteolysis.

Radiochemical design of polypeptides using metabolizable linkages would be attractive to enhance target-selective localization of radioactivity for diagnostic and therapeutic nuclear medicine. However, while use of ester bonds as the linkage allows selective release of the designed radiometabolite from covalently conjugated polypeptides after lysosomal proteolysis in nontarget tissues, low plasma stability of ester bonds causes a decrease in radioactivity levels of the target. In pursuit of new metabolizable linkages that provide stable attachment of radiolabels with polypeptide in plasma while facilitating rapid and selective release of designed radiometabolites of rapid urinary excretion in lysosomes, a new radioiodination reagent with L-lysine as the metabolizable linkage to liberate m-iodohippuric acid (L-HML) was designed and synthesized. Stabilities of the metabolizable linkage in serum and cleavabilities of the linkage in lysosomal proteolysis in hepatic cells were investigated after conjugation of [131I]-L-HML with galactosyl-neoglycoalbumin (NGA). For comparison, a radioiodination reagent with an ester bond to release m-iodohippuric acid (MIH) was conjugated with NGA under similar conditions. When incubated in human serum, [131I]-L-HML-NGA liberated less than 3% of the initial radioactivity after 24 h, whereas [125I]MIH-NGA released more than 60% of its radioactivity during the same interval. In biodistribution studies, [131I]-L-HML-NGA demonstrated radioactivity elimination from murine liver at a rate and excretion route similar to [125I]MIH-NGA. Analyses of murine urine after injection of [131I]-L-HML-NGA indicated a single radioactivity peak at fractions identical to those of m-iodohippuric acid. Biodistribution studies of radioiodinated NGAs with D-lysine or cadaverine as the linkages demonstrated a delayed elimination rate from murine liver with significantly higher radioactivity being excreted in the feces at 24 h postinjection. Thus, L-HML is the first reagent that allows stable attachment of radiolabel with polypeptide in serum while facilitating selective release of a radiometabolite with rapid urinary excretion from covalently conjugated polypeptides after lysosomal proteolysis at a rate similar to that of ester bonds. Thus, L-HML is potentially useful for the radioiodination of polypeptides for diagnostic and therapeutic purposes.

Albumins↗

A high performance liquid chromatographic method for determination of the radiochemical purity of iodohippuric acid [123I] injection.

A method for the separation of the radiopharmaceutical iodohippuric acid ([123I]IHA) from the two impurities produced in the labelling reaction, iodide (123I-) and iodobenzoic acid ([123I]IBA) has been developed using reversed-phase high performance liquid chromatography (h.p.l.c.). The effect of eluent pH on the separation of the three compounds was studied. An eluent consisting of methanol: 0.1 M acetic acid (30:70) adjusted to pH 4.0 with NaOH gave optimum phase capacity ratios of -0.21 for I-, 0.93 for IHA and 1.54 for IBA. On the chromatograph used, this corresponded to an analysis time of 4 min per sample. To recover 123I- from the column with a good peak shape, it was found necessary to include sodium iodide (1 mg/100 ml) in the eluent. The recoveries of 123I-123IHA and 123IBA from the column were found to be 100.6% (s.d. 1.3), 100.2% (s.d. 2.1) and 98.1% (s.d. 1.2) respectively (n = 10 for each compound). H.p.l.c. was compared with the standard thin layer chromatographic (t.l.c.) method of analysis on 10 preparations of [123I]IHA which gave a mean radiochemical purity of 99.1% (+/- 0.2 s.e.) by h.p.l.c. and 98.3% (+/- 0.2 s.e.) by t.l.c. This difference was found to be significant (P less than 0.05) and an explanation for this difference is proposed. A coefficient of variation of 0.1% on the results from the repeated analysis (n = 20) of one preparation of [123I]IHA, demonstrated that the h.p.l.c. method was capable of very high precision.

Chromatography, High Pressure Liquid↗

[A comparison of different methods of calculating clearances using 99mTc-mercaptoacetyltriglycine and 123I- or 131I-ortho-iodohippuric acid].

Using labelled MAG3 (n = 172) or OIH (n = 102) the results of three different techniques of calculating renal clearance were compared. The following techniques were used: Tauxe (single plasma concentration determination), Oberhausen (modified, combined partial body and plasma disappearance clearance) and Winkler (partial body clearance). For OIH, linear regression analysis revealed a positive correlation of Tauxe and Oberhausen clearances with a correlation coefficient (r) of 0.90 and a mean ratio (mean) Oberhausen/Tauxe clearances of 1.03. For MAG3, the Oberhausen values were found to be significantly lower than the Tauxe values with an equally good correlation. For this radiopharmaceutical the Winkler values were significantly higher than the Tauxe and Oberhausen values. For OIH, no such difference was noted. However, the correlation coefficient was significantly lower. Whereas with the Tauxe method, a mean ratio MAG3-/OIH clearances of 0.62 was observed in an earlier investigation, from the present data a ratio of 0.53 is calculated for the Oberhausen clearance. The difference between the Tauxe and Oberhausen clearances with MAG3 is of importance when comparing clearance values obtained with clearance calculation techniques and for establishing normal values for the MAG3 clearance.

Adult↗