[Estimation of effective half life of 131I in radioiodine therapy for Graves' disease using a single radioiodine uptake measurement].

Calculation of the absorbed radioiodine dose in the thyroid gland is a very important factor in 131I therapy for Graves' disease. In 131I therapy, the measurement of the effective half life (EHL) of radioiodine in the thyroid gland is indispensable for calculating the absorbed radioiodine dose. In some cases, however, EHL cannot be calculated because repeated measurements of thyroid uptake cannot be done. So, the authors developed a new method to estimate EHL using a single radioiodine uptake measurement. The activity of intrathyroidal 131I (thyroid uptake) and that of the surrounding area of the shielded thyroid (body background) were measured at 24 hours after the administration of 131I. The ratio of the value of body background to thyroid uptake was calculated. This ratio was multiplied by 100 and the calculated value was named the EHL-index. The relationship between actual measured EHL and the EHL-index was expressed by a regression line and/or a hyperbola. For the purpose of obtaining more actual values of EHL using the EHL-index, the new combined curve was composed of the regression line and the hyperbola. As for the value of calculated EHL compared with that of actual measured EHL, about 80 percent of calculated EHL values were within acceptable error ranges. These results indicate that EHL can be estimated by a single measurement 24 hours after administration of 131I. This method should be very useful in the therapy of Graves' disease with 131I when the thyroid measurement is performed only one time.

Differences in the side-chain metabolism of vitamin D3 between chickens and rats.

In vitro metabolism of 25-hydroxy-24-oxovitamin D3 was studied in kidney homogenates from vitamin D-supplemented chickens and rats. In chicken homogenates, 25-hydroxy-24-oxovitamin D3 was converted predominantly to 23,25-dihydroxy-24-oxovitamin D3, 24,25-dihydroxyvitamin D3, and 23,24,25-trihydroxyvitamin D3. In rat homogenates, 25-hydroxy-24-oxovitamin D3 was not converted to either 24,25-dihydroxyvitamin D3 or 23,24,25-trihydroxyvitamin D3, but it was converted to 23,25-dihydroxy-24-oxovitamin D3 and 23-hydroxy-24,25,26,27-tetranorvitamin D3. The latter metabolite was not produced by the chicken preparations. The stereochemical configuration at C-24 of the 24,25-dihydroxyvitamin D3 produced by chicken homogenates was determined to be S. This contrasts with the R configuration of 24,25-dihydroxyvitamin D3 produced by 24-hydroxylation of 25-hydroxyvitamin D3. These results suggest that chickens have an enzyme that can reduce the 24-oxo group to 24S-hydroxyl group, whereas rats do not.

Mechanism of the differentiating action of 25-hydroxyvitamin D3 endoperoxides in human myeloid leukemia cells (HL-60).

The action of 25-hydroxy-6,19-dihydro-6,19-epidioxyvitamin D3 [25-(OH)D3 endoperoxides, 2a and 3a] in inducing differentiation of human myeloid leukemia cells (HL-60) was studied by using their radioactive derivatives (2a' and 3a'). When HL-60 cells were incubated with the labeled endoperoxides (2a' and 3a') in serum-free RPMI 1640 medium, no radioactivity was incorporated into either the cytosol or the chromatin fraction of the cells. When the radioactive endoperoxide (2a') was incubated in the culture medium for 3 days, with or without HL-60 cells, about 45% of the compound was similarly converted to 19,25-dihydroxy-6,19-dihydro-6,19-epoxyvitamin D3 (4a) and about 10% to 25-hydroxy-6,19-epoxyvitamin D3 (6a). These two new vitamin D derivatives were synthesized chemically and tested for their biological activities. Both compounds (4a and 6a) were about 2 times as active as 25-(OH)D3 endoperoxides (2a and 3a) and about 7 times as active as 25-hydroxyvitamin D3 (1a) in inducing differentiation of HL-60 cells. The differentiating activity of these compounds was well correlated with their activity in binding to the cytosol receptor for 1 alpha, 25-dihydroxyvitamin D3 in HL-60 cells. The in vitro bone-resorbing activity of 25-hydroxy-6,19-epoxyvitamin D3 (6a) and 25-(OH)D3 endoperoxide (2a) was higher than that of 25-hydroxyvitamin D3 (1a), indicating that the differentiating activity also paralleled the bone-resorbing activity in these vitamin D derivatives. These results suggest that 25-(OH)D3 endoperoxides (2a and 3a) induce differentiation of HL-60 cells and bone resorption after being converted to these two compounds.