The Kinetics of Intravenously Injected Radioactive Vitamin B12: Studies on Normal Subjects and Patients with Chronic Myelocytic Leukemia and Pernicious Anemia

Abstract

1. Studies of the fate of intravenously injected radioactive vitamin B12 have been performed in patients with normal, low and high serum concentrations of vitamin B12. 2. Abnormal plasma disappearance curves were noted in chronic myelocytic leukemia, pernicious anemia in relapse and in remission, total gastrectomy and malabsorption syndrome. 3. In chronic myelocytic leukemia, the slow clearance of plasma radioactivity may be explained by the increased binding capacity of the plasma proteins for vitamin B12. 4. Plasma clearance of radioactivity is slower than normal in pernicious anemia, even in remission. The failure of the disappearance curve to return to normal in pernicious anemia in complete remission suggests the existence of a plasma "B12-transferase," whose function is to transfer circulating B12 to the tissues. The disappearance curves suggest that the amount of such "B12-transferase" is diminished in pernicious anemia, total gastrectomy and certain Cases of malabsorption syndrome. 5. A relationship between a hypothetical "B12-transferase" and intrinsic factor is discussed.

Co57 Vitamin B12 Clearance Studies in Pernicious Anaemia

“…It has been shown in this and other laboratories that plasma clearance of an intravenously injected tracer dose of radioactive vitamin BIZ is slower in patients with chronic myeloid leukaemia in relapse and other myeloproliferative disorders than in normal persons (Mollin et al 1956, Miller et al 1957, Mollin & Booth 1959, Ritz & Meyer 1960, Brody et al 1960, Hall 1961. Similar results have been reported in subjects with pernicious anaemia in relapse, with values falling between those reported for chronic myeloid leukaemia and normal persons (Mollin et al 1956, Miller et al 1957, Brody et al 1960, Hall et al 1962.…”

“…The authors suggested that plasma clearance is related to degree of serum unsaturation, which is high both in pernicious anaemia and chronic myelocytic leukaemia. Brody et al (1960) reported that four of five patients with malabsorption syndrome in relapse showed values similar to those in pernicious anaemia in relapse. They noted that in three patients with pernicious anaemia under treatment, plasma clearance of intravenously administered radioactive BIZ was more rapid but did not reach normal levels.…”

“…None of these suggestions has been proved or disproved. Brody et al (1960) suggested there may be a substance in plasma whose function is to permit transfer of circulating vitamin B12 from blood to tissues. They proposed that this hypothetical substance ('Biz-transferase') is present in adequate amounts in the normal person and is diminished in the blood of patients with pernicious anaemia in relapse and to a lesser degree in remission.…”

Coexistence of Pernicious Anaemia and Chronic Myeloid Leukaemia: An Experiment of Nature Involving Vitamin B12 Metabolism

“…The intravenous vitamin B,, disappearance study provides further support for the concept of deficient delivery of vitamin B,, to cells in patients with CML. WhenvitaminB,, isinjected intravenously into patients with CML, it disappears from the circulation at a slower rate than in normal subjects (Fig 2)' as previously reported by others (Mollin et al, 1956;Brody et al, 1960) suggesting that it is bound to a protein that does not deliver the vitamin to cells. When the sera of patients with CML is fractionated in DEAE cellulose after the in vitro addition of vitamin Biz, the normal a//3 ratio of 1/4 is reversed.…”

Plasma Clearance Studies of 57Co Vitamin B12 in Fish Tapeworm Anaemia

“…It has been shown in many laboratories that plasma clearance of an intravenously administered tracer dose of radioactive vitamin Blz is slower in patients with pernicious anaemia in relapse, malabsorption syndrome and fish tapeworm anaemia than in normal persons (Mollin et al 1956, Miller et al 1957, Brody et al 1960, Hall et al 1962. More recently it was demonstrated that in a group of 14 patients with untreated pernicious anaemia half the subjects had slow clearance rates while the remainder fell into the normal range (Meyer et al 1967).…”