Technetium-99m-1,2-bis[bis(2-ethoxyethyl) phosphino]ethane: human biodistribution, dosimetry and safety of a new myocardial perfusion imaging agent.

A novel 99mTc complex (1,2-bis[bis(2-ethoxyethyl)phosphino] ethane, 99mTc-tetrofosmin) has been developed to replace 201Tl in myocardial perfusion imaging. Biodistribution, safety and dosimetry of 99mTc-tetrofosmin were studied in 12 male volunteers, each at rest and during exercise. Safety parameters measured to 48 hr postinjection revealed no clinically significant long-term drug-related changes. Biodistribution was studied by acquiring whole-body or serial static images up to 48 hr postinjection. Technetium-99m-tetrofosmin shows good heart uptake (1.2%) with retention. Clearance is excellent from blood (< 5% by 10 min), liver (< 4.5% by 60 min) and lung. Sequestration of activity by skeletal muscle is enhanced during exercise. Radiation dosimetry calculations indicate that the effective dose, assuming a 3.5 hr bladder voiding period, is 32.9 x 10(-3) rad/mCi (8.9 x 10(-3) mSv/MBq) at rest and 26.7 x 10(-3) rad/mCi (7.1 x 10(-3) mSv/MBq) after exercise. Technetium-99m-tetrofosmin can produce high quality myocardial images from 5 min to several hours postinjection.

Pattern of 2-deoxy-2-[18F]-fluro-D-glucose accumulation in liver tumours: primary, metastatic and after chemotherapy.

Eight patients with liver metastases from adenocarcinoma of the colon or rectum, two with suspected hepatic metastases and one with primary hepatoma were studied with 2-deoxy-2-[18F]-fluro-D-glucose (18F-FDG) using positron emission tomography (PET). In five of the patients with metastatic tumour a second examination was performed four weeks after treatment with recombinant interleukin-2 (rIL2) and fluorouracil (5FU). In all tumours (one primary and eight metastatic) the radioactivity was seen to accumulate in a rim around each tumour with a large central area showing no uptake. In the five cases imaged after treatment with rIL2, the appearance of the tumour uptake was the same as before treatment. In the two cases of suspected but not proven metastases, no abnormal accumulation of 18F-FDG was seen.

Body fat in lean and overweight women estimated by six methods.

Body fat content of seven lean women (body mass index (BMI) 20.6 (SD 1.8) kg/m2) and seven overweight women (BMI 31.1 (SD 3.3) kg/m2) was estimated by six different methods: underwater weighing (UWW), body-water dilution (BWD), whole-body counting (40K), skinfold thickness (SFT), bioelectrical impedance (BEI) and magnetic resonance imaging (MRI). Using UWW as the reference method, the differences between percentage fat by each other method and the percentage fat by UWW were calculated for each subject. The mean difference was lowest for SFT and highest for BWD. MRI showed the lowest variability in individual results, and 40K the highest. 40K and BWD methods used in combination gave better agreement with UWW results than either 40K or BWD methods alone. There was a weak negative correlation between the difference from the UWW results and percentage fat in the SFT measurements, but not in the BWD, 40K, BEI or MRI measurements, suggesting that for these methods the assumptions involved produced no greater inaccuracy in the overweight women than in the lean women. In all subjects the BEI offered little improvement over the traditional SFT measurements. The agreement between MRI and UWW estimates in both lean and overweight women suggests that MRI may be a satisfactory substitute for the more established methods of body fat estimation in adult women.

Zinc metabolism in celiac disease.

The turnover of a radiolabeled (65Zn) pool of endogenous zinc was monitored by using a whole-body counter in eight patients with celiac disease (CD) and analyzed by using a two-compartment model. The biological half-life of the first compartment (1-3 wk postadministration) was similar in healthy volunteers (122 +/- 34 d, means +/- SD) and untreated patients (97 +/- 21 d). The second compartment in the patients (3-12 wk postadministration) was shorter (159 +/- 22.5 d. p less than 0.001) than were reference values (218 +/- 27 d) but increased (291 +/- 71 d) after the patients started gluten-free diets. The percentage absorption of 65Zn (9.25 kBq) from a test meal containing 31 mumol (2 mg) zinc was similar in untreated patients (30.0 +/- 13%) and healthy volunteers (32.5 +/- 12.4%). These data show that in mild untreated CD increased turnover and loss of endogenous zinc occurs whereas the absorption of zinc from a customary zinc intake may be normal. The pathophysiological basis of this loss was not investigated.

Inorganic zinc and the intestinal absorption of ferrous iron.

The effect of inorganic zinc on the absorption of inorganic iron (Fe+2) from a solution was assessed in two studies on healthy male volunteers. In the first study coadministration of 344 mumol of zinc had no effect (p less than 0.5) on the absorption of 842 mumol of radiolabeled Fe, assessed by the area under plasma Fe increment time curve during the 3 (AUC3) and 6 (AUC6) h postadministration (Fe alone AUC3 = 176.4 +/- 39.3; AUC6 = 387 +/- 101; Fe + Zn AUC3 = 180 +/- 33.1; AUC6 = 396 +/- 73.1 mumol.h-1.L-1), total plasma content of 59Fe, and whole-body retention of 59Fe. In the second study only the plasma appearance of Fe was monitored. After administration of 421 mumol of Fe alone, the AUC3 and AUC6 were 167 +/- 21.2 and 429.4 +/- 57 mumol.h-1.L-1, respectively; these were reduced to 56.4 +/- 17 and 119 +/- 34 (p less than 0.002) by 421 mumol Zn and further reduced by 1048 mumol Zn to 33 +/- 15 and 43.4 +/- 23.8 mumol.h-1.L-1 (p less than 0.001), respectively. It is concluded that Zn can impair the intestinal absorption of Fe.

Reduction of radiocaesium absorption by sheep consuming feed contaminated with fallout from Chernobyl.

Two compounds, a zeolite, clinoptilolite, and a ferrocyanide, potassium hexacyanocobalt (II) ferrate (II), were found to be the most effective adsorbers of caesium in vitro. When used in vivo they significantly reduced the absorption of caesium by sheep fed contaminated herbage. These compounds did not alter the rate of excretion of pre-absorbed caesium, which varied with the time from cessation of contamination.

Technetium-99m HM-PAO stereoisomers as potential agents for imaging regional cerebral blood flow: human volunteer studies.

A total of nine normal volunteer subjects were studied with three forms of [99mTc] hexamethylpropyleneamineoxime (HM-PAO), a potential cerebral blood flow imaging agent. One, the d,l isomer, showed 4.1% uptake in the brain which remained constant over 8 hr. There was good differentiation between uptake in gray and white matter on tomographic slices. We propose that this agent may allow regional cerebral blood flow imaging to be performed on a routine basis.

Effect of dihydroxylated metabolites of vitamin D3 on calcium absorption in uraemic man.

1. Peak 47Ca absorption and 7 day 47Ca retention were measured by a whole-body radioactivity counting technique in 10 haemodialysis patients before and after treatment with 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and 24,25-dihydroxycholecalciferol [24,25-(OH)2D3]. 2. Before treatment all patients had low peak 47Ca absorption and 7 day 47Ca retention. 3. After treatment with 1,25-(OH)2D3 (0 . 25-l microgram/day for 4-12 months) peak 47Ca absorption and 7 day 47Ca retention returned to normal. 4. After treatment with 24,25-(OH)2D3 (2 microgram/day for 4-12 months) peak 47Ca absorption and 7 day 47Ca retention remained at pretreatment levels. 5. It is concluded that physiological doses of 24,25-(OH)2D3 have no effect on calcium absorption or retention in uraemic man.