Effects of Radiopharmaceuticals on Radioenzymatic Assays of Aminoglycoside Antibiotics: Interference by Gallium-67 and Its Elimination

Abstract

Radionuclides currently used in clinical medicine were evaluated for their possible interference with radioenzymatic assays of aminoglycoside antibiotics. Of the radiopharmaceuticals tested, only 67Ga citrate interfered with the radioenzymatic assay of gentamicin. Radioenzymatic assay of serum samples obtained from patients receiving 67Ga yielded gentamicin concentrations falsely elevated by more than 1 ,Ag/ml for approximately 1 week after 67Ga admuinistration. A procedure was developed to eliminate 67Ga interference with radioenzymatic assays of aminoglycoside antibiotics. After 67Ga citrate was spotted onto phosphoceilulose filter disks, the filters were immersed in 7.2 N HCI, and radioactivity was removed by successive extractions of the acid phase with diisopropyl ether. After three extractions, less than 0.1% of the original radioactivity remained. Similar extraction of disks containing "C-adenylylated gentamicin or tobramycin or "C-acetylated amikacin had no effect on '4C radioactivity. The concentrations of aminoglycosides in serum standards supplemented with 67Ga citrate were determined accurately by radioenzymatic assays foilowed by extraction with diisopropyl ether. Concentrations of gentamicin in six serum samples from patients injected with 67Ga during gentamicin therapy, as determined by radioenzymatic assay and extraction, were within 9% of the results obtained by reassay of the same samples after the decay of 67Ga.With the increasing use of various radiopharmaceuticals in diagnostic nuclear scanning, interference with radioassays of drug levels in blood and other body fluids has become a problem. This difficulty has already been discussed with respect to the radioimmunassay of digoxin (3) and anti-DNA antibody (6).We recently encountered two patients who had been given "7Ga during a course of gentamicin therapy. Each had extraordinarily high levels of gentamicin in serum, exceeding 20 ,ug/ml, as determined by radioenzymatic assay. This experience suggested that 67Ga and possibly other radionucides currently used in clinical medicine might interfere with the radioenzymatic determination of aminoglycoside concentrations in serum. In this report, we evaluate the effects of five radiopharmaceuticals on the radioenzymatic assay of aminoglycoside antibiotics. We then describe a technique to eliminate the problem of 67Ga interference in radioenzymatic assays, using the method of Nachtrieb and Fryxell (2) for the extraction of radioactive gal- ['4C]acetyl coenzyme A was purchased from Amersham/Searle and diluted with unlabeled acetyl coenzyme A (P-L Biochemicals) to a specific activity of 4