The normal dietary and fluid intake and urinary and fecal excretion of 234 U and ${}^{238}{\rm U}$ were determined in humans under strictly controlled conditions in the Metabolic Research Ward at Hines Hospital. These values formed the basis of the metabolic balances of these uranium isotopes. The major pathway of 234 U and of ${}^{238}{\rm U}$ excretion was via the intestine while the urinary 234 U and ${}^{238}{\rm U}$ were very low, averaging 2% of the total excretion. The uranium balances were roughly in equilibrium. These data were used in combination with measurements of tissue concentrations of uranium from nonoccupationally exposed humans to calculate steady-state uptake factors for environmental exposure to uranium isotopes during baseline conditions of a normal dietary intake.

Metabolic balances of 210 Po and 210 Pb were determined under strictly controlled dietary conditions in adult males. The intakes of the two nuclides were due to the dietary contents of these radioisotopes, inhalation from the atmosphere, and smoking of cigarettes. No additional radioisotope was given. The mean dietary intake of 210 Pb was 1.25 pCi/day and of 210 Po, 1.63 pCi/day. The major pathway of excretion of both nuclides is via the gastrointestinal tract and the urinary excretion is much lower. The total excretions of 210 Pb and 210 Po were greater than the dietary intake and the overall balances were -0.28 and -0.16 pCi/day for the two nuclides, respectively, during a low calcium intake. The 210 Pb balances did not change significantly when the calcium intake was increased 7- to 10-fold except for one patient in whom the balance became more negative. The 210 Po balance was more negative during calcium intakes of 800 and 2200 mg than during a low calcium intake of 200 mg/day. The urinary and fecal excretions of the two radionuclides were not affected by the intake of sodium fluoride, while the diuretic compound Hydrodiuril appeared to decrease the fecal 210 Pb excretion.

A study was performed in man to determine the rate of exit of calcium from the plasma compartment and its reentry utilizing the integro-differential equation method of tracer analysis. The studies have shown that both the rate of exit of calcium from plasma as its return are extremely rapid. The analysis indicates that most of the calcium which exits from the vascular system returns within 30 min. The external exchangeable calcium volume has been calculated as a function of time. The 30-min exchangeable volume is approximately three times that of the plasma calcium compartment. All rates and volumes were significantly increased in a patient with Paget's disease of the bone.

The dietary intake and the urinary and fecal excretion of naturally occurring 226 Ra and 226 Ra balances were determined in man under strictly controlled dietary conditions. These provided the basis for calculating the 226 Ra balances. These balance studies were carried out during a low calcium intake, during the addition of different amounts of calcium given as calcium gluconate, and during the intake of milk. 226 Ra balances were also determined during conditions which affect the metabolism of calcium: during intravenous infusions of stable strontium, during infusions of ACTH, and during total calorie starvation. During a low calcium intake of an average of 243 mg/day, the urinary 226 Ra excretion averaged 0.016 pCi/day, during a calcium intake of 1300 mg or 2600 mg/day, given as calcium gluconate, the urinary 226 Ra excretion did not increase, while during supplementation of the diet with milk the urinary 226 Ra excretion increased. On all calcium intakes the urinary 226 Ra excretion averaged 3% of the total excretion except that it was 12% on milk intake. The major pathway of 226 Ra excretion was via the intestine and the 226 Ra balances were in equilibrium under all study conditions. There was no correlation between the urinary 226 Ra and the urinary calcium excretion.

The secretion of <tex-math>${}^{85}{\rm Sr}$</tex-math> and <tex-math>${}^{47}{\rm Ca}$</tex-math> from the vascular space into the intestine was determined in rats as a function of time during both feeding and fasting. <tex-math>${}^{85}{\rm Sr}$</tex-math> and <tex-math>${}^{47}{\rm Ca}$</tex-math> were injected intravenously, and the rats were sacrificed after 1/2, 1, 2, 4, and 24 hours. The gastrointestinal radioisotope content was measured in six separate segments. During feeding, slightly more <tex-math>${}^{47}{\rm Ca}$</tex-math> than <tex-math>${}^{85}{\rm Sr}$</tex-math>, 5.1% vs 4.6% of the dose, respectively, was present at 1/2 hour in the gastrointestinal tract. At 4 hours the <tex-math>${}^{85}{\rm Sr}$</tex-math> in the intestine rose to 7.0%, while <tex-math>${}^{47}{\rm Ca}$</tex-math> had increased only very slightly. Between 4 and 24 hours the excretion of both isotopes via the intestine increased, but the increase in <tex-math>${}^{85}{\rm Sr}$</tex-math> excretion was greater than that of <tex-math>${}^{47}{\rm Ca}$</tex-math>, the values being 11% and 8.6% of the dose at 24 hours, respectively. Fasting decreased the secretion of both isotopes into the intestine at all time intervals, and this effect was more marked for <tex-math>${}^{47}{\rm Ca}$</tex-math> than for <tex-math>${}^{85}{\rm Sr}$</tex-math>. At 24 hours, during fasting, the intestinal excretion of <tex-math>${}^{85}{\rm Sr}$</tex-math> was less than half of the feeding level, while the intestinal excretion of <tex-math>${}^{47}{\rm Ca}$</tex-math> was less than one-third of that during feeding, resulting in a <tex-math>${}^{85}{\rm Sr}/{}^{47}{\rm Ca}$</tex-math> ratio of 2.0 during fasting vs 1.3 during feeding.

The effect of orally and of intravenously administered stable strontium on 90 Sr metabolism was investigated in man under strictly controlled dietary conditions. The oral dose of stable strontium averaging 1517 mg/day was given as the lactate for 24-48 days. Intravenous infusions of stable strontium as the gluconate were given in 500 ml 5% glucose in water over 4 hours on 6 consecutive days. The amounts of stable strontium infused per day were 318, 612, 954, and 1200 mg, respectively. 90 Sr and calcium balances were determined before and during the oral and intravenous administration of stable strontium. Stable strontium given orally or intravenously increased the urinary 90 Sr excretion. This increase was greater when stable strontium was given intravenously than orally, the average factor of increase being 3 and 1.65 in the two studies, respectively. The fecal 90 Sr excretions did not increase during either oral or intravenous administration of stable strontium. The 90 Sr balances changed little during the oral intake of stable strontium while they became more negative during the infusions of stable strontium. The urinary calcium increased during the oral or intravenous administration of stable strontium and this increase was greater when stable strontium was given intravenously than orally.

The excretion of <tex-math>${}^{47}{\rm Ca}$</tex-math> and <tex-math>${}^{85}{\rm Sr}$</tex-math> from the vascular space into the intestine was determined in three weight groups (100, 250 and 400 g) of Sprague-Dawley rats during feeding and fasting. Both isotopes were injected intravenously and the animals were sacrificed 24 hours following administration of the dose. During feeding, <tex-math>${}^{85}{\rm Sr}$</tex-math> was excreted into the intestine to a slightly greater extent than <tex-math>${}^{47}{\rm Ca}$</tex-math> and the intestinal excretion of both isotopes increased to some extent with age. During fasting, considerably less of both isotopes was excreted via the intestine but the increase in intestinal excretion with age was more marked. The decrease in the intestinal excretion during fasting was greater for <tex-math>${}^{47}{\rm Ca}$</tex-math> than for <tex-math>${}^{85}{\rm Sr}$</tex-math>, so that the <tex-math>${}^{85}{\rm Sr}/{}^{47}{\rm Ca}$</tex-math> ratio increased from 1.3 during feeding to 2.2 during fasting. <tex-math>${}^{85}{\rm Sr}$</tex-math> was excreted in urine to about the same extent as in the feces during feeding and fasting while the urinary excretion of <tex-math>${}^{47}{\rm Ca}$</tex-math> was considerably lower than the fecal <tex-math>${}^{47}{\rm Ca}$</tex-math> excretion during both study conditions. The uptake of <tex-math>${}^{85}{\rm Sr}$</tex-math> in bone was lower than that of <tex-math>${}^{47}{\rm Ca}$</tex-math> during both feeding and fasting but the bone uptake of both isotopes was significantly greater during fasting than feeding. This increase in bone uptake corresponded to the decrease in urinary and fecal excretions of the two radioisotopes during fasting.

The effect of aluminum phosphate gel on the absorption of radioactive strontium was studied in man under constant and controlled dietary conditions on a low calcium intake in 11 of the 13 cases. Studies previously performed in this laboratory have shown that 100 ml of this compound given immediately prior to the oral administration of ${}^{85}{\rm Sr}$ decreased the absorption of radiostrontium by an average of 87%. In the present investigation, the effectiveness of aluminum phosphate gel, given 1/2 hour and 1 hour after the ingestion of radiostrontium, was studied on the absorption of this radioisotope in man. The absorption of ${}^{85}{\rm Sr}$ was decreased by an average of 57% when aluminum phosphate gel was given at 1/2 hour, and by an average of 43% when this compound was given at 1 hour. Amounts of 100 ml of aluminum phosphate gel were as effective as 200 ml or 300 ml. The absorption of ${}^{85}{\rm Sr}$ was decreased in all patients receiving a low calcium intake and in one patient receiving a high calcium intake. There was no decrease in ${}^{85}{\rm Sr}$ absorption in a second patient maintained on a high calcium intake. The suitability of this nontoxic, well-tolerated antacid for the prevention of absorption of radioactive strontium in case of acute exposure to this radioisotope in man has been discussed.

Ten experiments were performed in rats to study the effect of aluminum phosphate gel on the uptake of radiostrontium in bone. Aluminum phosphate gel was given by gastric intubation, immediately prior to, immediately after, and at 10 minutes, 30 minutes, and 1 hour after the oral administration of ${}^{85}{\rm SrCl}{}_{2}$ . The uptake of ${}^{85}{\rm Sr}$ in bone was determined in groups of rats sacrificed at 1 hour and at 24 hours following the oral ${}^{85}{\rm Sr}$ administration. The ${}^{85}{\rm Sr}$ blood levels and the ${}^{85}{\rm Sr}$ content in the gastrointestinal tract were determined in addition to the ${}^{85}{\rm Sr}$ bone uptake in groups of rats sacrificed at 1 hour following the administration of the radioisotope. In the rats sacrified at 1 hour, aluminum phosphate gel, given either immediately prior to or immediately after the oral dose of ${}^{85}{\rm Sr}$ , decreased the ${}^{85}{\rm Sr}$ blood level by an average of 85% and the bone uptake by an average of 88%. At 10 minutes, ${}^{85}{\rm Sr}$ uptake in bone was decreased by an average of 62%, while at 1/2 hour the decrease averaged only 35%. When aluminum phosphate gel was given at the same time intervals to rats sacrificed at 24 hours, the results were similar. However, when aluminum phosphate gel was given at 1 hour after the oral dose of ${}^{85}{\rm Sr}$ , to rats sacrified at 24 hours, the uptake of the radioisotope in bone was unchanged. The decrease in ${}^{85}{\rm Sr}$ concentration in blood and bone was associated with a corresponding increase of the ${}^{85}{\rm Sr}$ content in the gastrointestinal tract. These studies show that aluminum phosphate gel is effective in decreasing the uptake of ${}^{85}{\rm Sr}$ in bone as a result of decreased absorption of radiostrontium.

Parenterally administered stable strontium has been shown to be effective in decreasing the radiostrontium body burden in animals, whereas stable calcium is ineffective. In the present study, the effects of intravenously infused stable strontium and stable calcium, used in equimolar amounts as the gluconate, on urinary ${\rm Sr}^{85}$ excretion were investigated in man under constant and controlled dietary conditions. All patients received a low-calcium diet on the Metabolic Research Ward. A single tracer dose of ${\rm Sr}^{85}{\rm Cl}_{2}$ was given intravenously on the first day of the control and experimental studies. Infusions of stable strontium and stable calcium were given on 3 successive days in separate studies, the first infusion being given on the day of administration of ${\rm Sr}^{85}$ . The ${\rm Sr}^{85}$ plasma levels and the urinary and fecal excretions were determined in the control, the stable strontium, and the stable calcium studies. Both stable strontium and stable calcium increased the urinary excretion of radiostrontium, infusions of stable strontium being somewhat more effective than infusions of stable calcium. Also, after the discontinuation of the stable strontium infusions, the urinary ${\rm Sr}^{85}$ excretions remained higher for several days than in the control and the stable calcium studies, stable strontium resulting in a significantly higher 10-day cumulative urinary ${\rm Sr}^{85}$ excretion than stable calcium. There was no effect of intravenous stable strontium or stable calcium on fecal ${\rm Sr}^{85}$ excretion.