In vitro radioautographic studies of the biodistribution of radiopharmaceuticals on blood elements

In the present study evaluated the binding of the radiopharmaceuticals sodium pertechnetate (Na (99m)TcO4), methylenediphosphonic acid (99m)Tc-MDP)) and glucoheptonate acid (99m)Tc-GHA)) to blood elements using centrifugation and radioautographic techniques. Heparinized blood was incubated with the labelled compounds for 0, 1, 2, 3, 4, 6 and 24 h. Plasma (P) and blood cells (BC) were isolated and precipitated with 5 percent trichloroacetic acid (TCA), and soluble (SF) and isoluble fractions (IF) were separated. Blood samples were prepared (0 and 24 h) and coated with LM-1 radioautographic emulsions and percent radioactivity (percent rad) in P and BC was determined. The binding of Na (99m)TcO4 (percentrad) to P was 61.2 percent (0 h) and 46.0 percent (24 h), and radioautography showed 63.7 percent (0 h) and 43.3 percent (24 h). The binding to BC was 38.8 percent (0 h) and 54.0 percent (24 h), and radioautography showed 36.3 percent (0h) and 56.7 percent (24 h), and radioautography showed 36.3 percent (0 h) and 56.7 percent (24 h). (99m) Tc-MDP study presented 91.1 percent (0 h) to P and 87.2 percent (24 h), and radioautography showed 67.9 percent (0 h) and 67.4 percent (24 h). The binding to BC was 8.9 percent (0 h) and 12.8 percent (24 h), and radioautography showed 32.1 percent (0 h) and 32.6 percent (24 h). (99m)Tc-GHA study was 90.1 percent (0 h) to P and 79.9 percent (24 h), and radioautography showed 67.2 percent (0 h) and 60.1 percent (24 h). The binding to BC was 9.9 percent (0 h) and 20.1 percent (24 h), and radioautography showed 32.8 percent (0 h) and 39.9 percent (24 h). The comparasion of the obtained results suggests that the binding to plasma and blood cells in the two techniques used (radioautography and centrifugation) qualitatively in accordance.

Plasma clearance and biodistribution of oxidatively modified 99mTc-Beta-VLDL in rabbits

The biodistribution and removal from plasma (measured as fractional clerance rate, FCR, per hour) of native and oxidatively modified (99m)technetium-labeled Beta-very low density lipoprotein ((99m)Tc-Beta-VLDL)) were investigated in hypercholesterolemic (HC) and control (C) three-month old New Zealand rabbits. The intracellular accumulation of Beta-VLDL labeled with (99m)Tc was studied in vitro in THP-1 cells and monocyte-derived macrophages isolated from rabbits. After intravenous injection into C rabbits, copper-oxidized Beta-VLDL ((99m)Tc-ox-Beta-VLDL)) was cleared from the circulation faster (0.362 + 0.070/h) than native Beta-VLDL ((99m)Tc-nat-Beta-VLDL, 0.241 + 0.070/h)). In contrast, the FCR of (99m)Tc-ox-Beta-VLDL in HC rabbits was lower (0.100 + 0.048/h) than that of (99m)Tc-nat-Beta-VLDL (0.163 + 0.043/h). The hepatic uptake of radiolabeled lipoproteins was lower in HC rabbits (0.114 + 0.071 percent injected dose/g tissue for (99m)Tc-nat-Beta-VLDL and 0.116 + 0.057 percent injected dose/g tissue for (99m) Tc-ox-Beta-VLDL) than in C rabbits (0.301 + 0.113 percent injected dose/g tissue for (99m)Tc-nat-Beta-VLDL and 0.305 + 0.149 percent injected dose/g tissue for ((99m)Tc-ox-Beta-VLDL). The uptake of (99m)Tc-nat-Beta-VLDL and (99m)Tc-ox-Beta-VLDL by atherosclerotic aorta lesions isolated from HC rabbits ((99m)Tc-nat-Beta-VLDL:0.033 + 0.012 percent injected dose/g tissue and (99m)Tc-ox-Beta-VLDL: 0.039 + 0.017 percent injected dose/g tissue) was higher in comparison to that of non-atherosclerotic aortas from C rabbits (99m)Tc-nat-Beta-VLDL: 0.023 + 0.010 percent injected dose/g tissue and (99m)Tc-ox-Beta VLDL: 0.019 + 0.010 percent injected dose/g tissue). However, (99m) Tc-nat-Beta-VLDL and (99m)Tc-ox-Beta-VLDL were taken up by atherosclerotic lesions at similar rates. In vitro studies showed that both monocyte-derived macrophages isolated from rabbits and THP-1 macrophages significantly internalized more (99m)Tc-ox-Beta-VLDL than (99m)Tc-nat-Beta-VLDL. These results indicate that in cholesterol-fed rabbits (99m)Tc-ox-Beta-VLDL is slowly cleared from plasma and accumulates in atherosclerotic lesions. However, although the extent of in vitro uptake of (99m)Tc-ox-Beta-VLDL by macrophages was high, the in vivo accumulation of this radiolabeled lipoprotein by atherosclerotic lesions did not differ from that of (99m)Tc-nat-Beta-VLDL.