Search

Labeling of F(ab′) 2 with 99 m Tc was investigated. The best labeling procedure for F(ab′) 2 was then applied to IgG and Fab. Stannous ion was used as the reducing agent for 99m TcO 4 − and free DTPA was used as a competing reagent to prevent colloid formation and loosely bound 99m Tc. The competition reactions revealed two 99m Tc binding sites for F(ab′) 2 and IgG. One is a high capacity, low affinity site. This accounts for 76 and 84% of total IgG and F(ab′) 2 binding sites. The labeling of these sites can be prevented if the antibody is labeled in the presence of free DTPA. The second site is a low capacity, high affinity site. The labeling of these sites cannot be prevented by free DTPA. Fab, unlike IgG and F(ab′) 2 , does not have an appreciable percentage of high affinity sites. The determination of sulfhydryl groups using Ellman's reagent indicates the production of 5.5, 4.2 and 0.9 sulfhydryl groups when IgG, F(ab′) 2 and Fab were exposed to 56 μg/mL SnCl 2 · 2H 2 O. These sulfhydryl groups may be the source of the high affinity binding. Biodistribution in mice for 9 99m Tc labeled F(ab′) 2 and F(ab′) 2 -DTPA, both prepared in the presence of excess free DTPA, was similar to that of F(ab′) 2 -DTPA- 111 In.

We examined the distribution of three tritiated ligands and two radioiodinated ligands for their ability to localize in the pancreas of rat and rabbit. The ligands examined are selective for the α- and β-adrenoceptors and the muscarinic acetylcholine receptor. Of the ligands examined, the results indicate that only (R) 3H-3-quinuclidinyl benzilate (QNB) localized in the pancreas by the receptor-mediated mechanism. The % dose/g tissue, the pancreas-to-blood and pancreas-to-liver ratios are such that a 18F-labeled derivative of QNB should provide images of the pancreas.

Radiolabeled analogues of 3-quinuclidinyl benzilate (QNB) localize in the myocardium by virtue of ligand-receptor interactions. The radioiodinated derivative exhibits less favorable non-receptor interactions than tritiated QNB in the myocardium, probably due to increased lipophilicity. In order to prevent intracellular localization and partitioning into lipid membranes, we prepared the N-methyl quaternary analogue of the iodinated derivative [ 125 I]3-quinuclidinyl 4-iodobenzilate. In vitro and in vivo results indicate that the quaternization reduces the affinity of the analogue to a value too low for advantageous receptor-mediated localization.

In an effort to evaluate receptor binding drugs for their potential as gamma labeled radiopharmaceuticals suitable for clinical heart scanning, in vivo data were compared with the results obtained from a theoretical model. The distribution of selected tritium-labeled, receptor-binding radiotracers was studied in animals to determine if the heart to blood ratios agree with those obtained using a theoretical model of receptor binding. In general, the in vivo studies agree with the theoretical model when the concentration of the radiotracer in the heart is due to specific receptor binding. The use of the theoretical model for a first approximation followed by in vivo biodistribution studies is an efficient strategy to select those few from among the large number of receptor binding compounds that will ultimately yield an efficacious radiopharmaceutical to study receptor changes in the intact human heart.