Simultaneous free and bound radioactive vitamin B₁₂urinary excretion test

Abstract

sYNoPsis The absorption of vitamin B12 following the simultaneous administration of 58Co B12 and a complex of 57Co B12 with human gastric juice was assessed by measurement of urinary excretion of radioactivity. Sixteen control subjects, 13 patients with pernicious anaemia, and four who had had total gastrectomy were studied. The method proved a reliable means of detecting those with intrinsic factor deficiency.The urinary excretion test introduced by Schilling (1953) for assessing the absorption of vitamin B12 is useful in the investigation of patients suspected of having vitamin B12 deficiency (Van Kampen and Graafland, 1959;Adams and Seaton, 1961). In this test a small oral dose of vitamin B12 labelled with radioactive cobalt is given to the patient. Simultaneously a large intramuscular dose of non-radioactive B12 is administered to block the body stores and to flush out the labelled vitamin into the urine. The radioactivity excreted in the following 24 or 48 hours is determined and provides a measure of the amount of the oral dose which has been absorbed. When the radioactivity excreted by the patient is less than that of control subjects the test is repeated a few days later with the addition of potent intrinsic factor. If the fraction of the oral dose excreted in the urine is now increased by at least a factor of 2, the patient is presumed to be deficient in intrinsic factor. Katz, DiMase, and Donaldson (1963) have described a diagnostic procedure which combines the two parts of the Schilling test. Vitamin B12 labelled with 58Co is given orally to the patient together with vitamin B12 labelled with 60Co, bound to normal human gastric juice. A large intramuscular dose of non-radioactive B12 is simultaneously administered and the amounts of`8Co and 60Co excreted in the urine are separately determined. Thus both the absorption of B12 and the effect of intrinsic factor may be assessed.The present work describes a modification of this technique in which 57Co B12 iS substituted for 60Co B12 thus reducing the dose of radiation to the patient. Normal subjects, patients with pernicious anaemia, and patients with total gastrectomy were investigated.

Evaluation of a Dual Radioisotope Urinary Excretion Test in the Diagnosis of Pernicious Anaemia

“…In the previous study [2] all normals indicated a 57Co/58Co ratio of less than 1.6, while all those with PA, gave a ratio greater than 2.0. The results of studying a larger group of patients seem to indicate a slight overlap between the normal and pathological ranges, the range for patients with PA being 1.7 to 9.6, and for the control group 0.8 to 1.8.…”

“…Since 67Co emits y rays with energies of 0.12 MeV compared with 68Co which emits y rays with energies of 0.81 MeV the amount of each isotope in the total urine collection can be readily determined by altering the discriminator bias settings on an associated scaler, and solving the simultaneous equations described by V eall and V etter [7], for the assay of a liquid containing a mixture of two radioisotopes. The series includes 29 patients whose results were previously published [2]. The patients included in the pernicious anaemia group showed a clinical picture con sistent with the diagnosis supported by the finding of most of the following abnormalities : a macrocytic peripheral blood picture, a megaloblastic bone marrow, a low scrum B,2 level, a histamine fast achlorhydria or a satisfactory response to B12 therapy.…”

“…Freeze dried ampoules of vitamin Bla labelled with s,Co and with S8Co each with a specific activity of 1 ftcl/cg B,2 were obtained from the Radiochemical Centre, Amersham. Oral doses of 58CoB12 and 57CoB,2 bound to human gastric juice (57CoB12HJG), each with concentrations of 0.25 fig Bl2 in 20 ml water were prepared as described previously [2], Usually 12 radioactive doses, and appropriate stand ards, of the unbound and bound Bl2 were prepared at a time and these were stored at -15°C until required.…”

“…In a preliminary communication, Bell et al [2], described a modification of this double isotope technique using 57CoB12 bound to human gastric juice and free 58CoB12, which replaced 60Co resulting in a lower radiation dose to the patient. This dual radioisotope test for investigation of vitamin B12 absorption has been further evaluated and the results are now described.…”

Plasma Radioactivity Following Simultaneous Oral Administration of Intrinsic Factor-Bound and Free Radioactive Vitamin B₁₂

“…The bound : free ratio of plasma radioactivity did not exceed 1.6 in any normal subject, and this has, therefore, been accepted as the upper Measurement of plasma radioactivity in vitamin B12 absorption stud ies is well documented [4,6] and the diagnostic value of this test has be come established in recent years. Bell et al [2] and B ell and L ee [3] described a test, based on the method of K atz et al [9], which com bined the two stages of the urinary excretion (Schilling) test. The basis of this test is the simultaneous administration of radioactive Co-labelled vitamin B I2 in 2 isotopic forms, one of which is 'free' while the other is 'bound' to normal human gastric juice.…”