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Evaluation of [Iodine-125] N,N,N'-Trimethyl-N'-[2-Hydroxy-3-Methyl-5-Iodobenzyl]-1,3-Propanediamine Lung Uptake Using an Isolated-Perfused Lung Model

Division of Nuclear Medicine, Columbia-Presbyterian Medical Center, New York, New York
Medical Department, Brookhaven National Laboratory Upton, New York
Arthritis Unit, Massachusetts General Hospital, Boston, Massachusetts

Correspondence: For reprints contact: Daniel O. Slosman. MD, Département de Médecine Nucléaire, Hôpital Cantonal Universitaire Genevois, 1211-Genève-4, Switzerland.

ABSTRACT

Lung uptake of N,N,N'-trimethyl-N'42-Hydroxy-3-methyl-5-iodobenzyl]-1,3-propanediamine (HIPDM) has been reported, but the mechanism of this process has not yet been established. Thus, single-pass [¹²⁵I]HIPDM accumulation was studied in rat lungs perfused with a Krebs-Ringer bicarbonate buffer containing 4.5% bovine albumin. Iodine-125 HIPDM lung accumulation was monitored by the percent of extraction per gram of lung tissue. Iodine-125 HIPDM lung uptake did not appear to occur by simple diffusion. As the time of perfusion was increased from 2 to 15 min, the rate of uptake of 2 µM [¹²⁵I]HIPDM decreased by 40%. During a 2-min perfusion, 98.6% ± 6.7 (n = 8) extraction was observed with 2 µM [¹²⁵I] HIPDM, but only 38% ± 2.0 (n = 3) was extracted when the [¹²⁵I]HIPDM concentration was 1 mM. The addition of 1 mM chlopromazine, propranolol or imipramine also decreased [¹²⁵I]HIPDM lung uptake to 43.0% ± 1.5, 51.4% ± 2.2, and 49.8% ± 0.8, respectively, (each n = 4 – 6, p < 0.001). Cold (4°C) had little effect on pulmonary accumulation (77.7% ± 7.4, n = 5, p < 0.01), and the addition of ouabain or the use of sodium-free medium had no effect. Thus, pulmonary [¹²⁵I]HIPDM accumulation does not appear to occur by sodium-dependent active transport. Rather, its uptake appears to be similar to the uptake of other basic amines, such as propranolol and imipramine, which are known to bind by physico-chemical interactions to pulmonary endothelial cell membranes and reflect pulmonary vascular surface area.