Bone extraction and blood clearance of diphosphonate in the dog

Abstract

The transcapillary extraction of diphosphonate, as [99mTc]EHDP, a substance used in bone scanning and for management of certain metabolic bone diseases, has been examined. The maximum instantaneous extraction for [99mTc]EHDP was 0.27 +/- 0.05 (mean +/- SD, N = 10) and the net extraction at 5 min was 0.18 +/- 0.05 (N = 10). The permeability ratio of [99mTc]EHDP to the freely diffusible compound, sucrose, using the formula PS = -Fs loge (1 - Emax), was 0.71. This is similar to the ratio of diffusion coefficients of EHDP to sucrose, which is estimated to be 0.78. These results suggest that the mechanism by which [99mTc]EHDP passes through the capillaries in bone is passive diffusion. Tissue level estimations of EHDP confirm a rapid blood clearance associated with an increase in the rate of urinary excretion; the level of [99mTc]EHDP in bone, however, remains constant. The fractional excretion of [99mTc]EHDP was 27.3 +/- 2.0% in control dogs and was unchanged by thyroparathyroidectomy and subsequent infusion of parathyroid hormone.

Fig. 1

Examples of outflow dilution curves, from one dog, of albumin, sucrose, and EHDP following a 47-s injection into nutrient artery (upper) with extraction derived from Eqs. 2 and 5 (lower).

Fig. 2

Examples of outflow dilution curves, from one dog, of albumin, EHDP, and strontium to demonstrate greater extraction of smaller molecule strontium.

Fig. 3

Example of a plasma clearance curve for EHDP over 4 h, showing rapid plasma clearance.

Fig. 4

Mean percentage of injectate in various tissues of the body at 1, 2, 3, and 4 h, showing decreasing blood, increasing urine, but constant bone uptake.

Fig. 5

Mean ratios of radioactivity of tissue to that of plasma at 1, 2, 3, and 4 h, from Eq. 10.