Abstract
Circulating biogenic amines, such as serotonin or norepinephrine, are cleared by the lung and can be considered as indicators of pulmonary endothelial integrity. An iodinated norepinephrine analogue, metaiodo-benzylguanidine (MIBG), is extracted in the lung by an active, saturable transport system. In order to investigate the use of MIBG lung extraction to detect minimal,lung endothelial cell lesions, an experimental model of initial pulmonary vascular lesions was developed in rats using repeated daily intraperitoneal injection of bleomycin (BLM: 2 U/100 g body weight) over a 5-day period. At this time, a significant decrease of serum angiotensin-converting enzyme activity, an index of endothelial cell metabolism, was observed (214±11 U/ml in controls as compared with 182±11 U/ml in BLM-treated rats,P < 0.05); electron microscopy showed the presence of typical but minimal endothelial cell lesions (blebbing). MIBG extraction (%EMIBG) was measured using the isolated perfused lung model after a 10-min steady-state period and 2 min of perfusion with123I-MIBG (0.1 μCi/ml) and125I-labelled human serum albumin (HSA) (0.2 μCi/ml). Intraperitoneal administration of BLM to rats for 5 days resulted in a significant decrease in pulmonary extraction of MIBG. %EMIBG declined from a control value of 24.7%±1.1% in controls to 19.3%±1.6% in BLM-treated rats (n=27,P<0.05; -21.2%). HSA lung extraction, used as an estimate of nonspecific residual lung activity, was not different in the lungs of BLM-treated rats as compared with controls. Because measurements of MIBG lung extraction (%EMIBG) were able to demonstrate the presence of minimal endothelial cell lesions due to the BLM toxicity, MIBG is an index of pulmonary endothelial cell function.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adamson IYR, Bowden DH (1974) The pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Am J Pathol 77:185–198
Catravas JD, Lazo JS, Gillis CN (1981) Biochemical markers of bleomycin toxicity: clearance of [14C]-5-hydroxytryptamine and [3H]-norepinephrine by rabbit lung in vivo. J Pharmacol Exp Ther 217:524–529
Catravas JD, Lazo JS, Dobuler KJ, Mills LR, Gillis CN (1983) Pulmonary endothelial dysfunction in the presence or absence of endothelial cell injury induced by intratracheally injected bleomycin in rabbits. Am Rev Respir Dis 128:740–746
Cooper JAD Jr, White DA, Matthay RA (1986) Drug induced pulmonary disease. Part 1: cytotoxic drugs. Am Rev Respir Dis 133:321–340
Dargent F, Gardaz J-P, Morel P, Suter PM, Junod AF (1985a) Effects of atelectasis and vascular occlusion on the simultaneous measurement of serotonin and propranolol pulmonary extraction in dogs. Clin Sci 69:279–286
Dargent F, Neidhart P, Bachmann S, Suter PM, Junod AF (1985b) Simultaneous measurement of serotonin and propranolol pulmonary extraction in patients after extracorporeal circulation and surgery. Am Rev Respir Dis 131:242–245
Dollery CT, Junod AF (1976) Concentration of (+/-)-propranolol in isolated, perfused lungs of rat. Br J Pharmacol 57:67–71
Gillis CN (1986) Pharmacological aspects of metabolic processes in the pulmonary circulation. Ann Rev Pharmacol Toxicol 26:183–200
Giri SN, Nakashima JM, Curry DL (1985) Effects of intratracheal administration of bleomycin or saline in pair-fed and controlfed hamsters on daily food intake and on plasma levels of glucose, cortisol, and insulin, and lung levels of calmodulin, calcium, and collagen. Exp Mol Pathol 42:206–219
Johansen KB, Marstein S, Aas P (1987) Automated method for the determination of angiotensin-converting enzyme in serum. Scand J Clin Lab Invest 47:411–414
Junod AF (1972) Uptake, metabolism and efflux of14C-5-hydroxy-tryptamine in isolated perfused rat lungs. J Pharmacol Exp Ther 183:341–355
Junod AF (1985) 5-hydroxytryptamine and other amines in the lungs. In: Handbook of physiology. The respiratory system 1. pp 337–349
Lazo JS (1986) Endothelial injury caused by antineoplastic agents. Biochem Pharmacol 35:1919–1923
Lazo JS, Catravas JD, Gillis CN (1981) Reduction in rabbit serum and pulmonary angiotensin converting enzyme activity after subacute bleomycin treatment. Biochem Pharmacol 30:2577–2584
Morel DR, Dargent F, Bachman M, Suter PM, Junod AF (1985) Pulmonary extraction of serotonin and propranolol in patients with adult respiratory distress syndrome. Am Rev Respir Dis 132:479–484
Pitt BR, Hadden P, Gillis CN (1987) In line assessment of pulmonary extraction of125-metaiodobenzylguanidine (MIBG) by perfused rabbit lung. Fed Proc 46:665
Slosman DO, Polla BS (1988) In vivo systemic administration of bleomycin in the rat activates monocytes and primes alveolar macrophages for superoxide generation. Am Rev Respir Dis 137:A123
Slosman DO, Davidson D, Brill AB, Alderson PO (1986) Pulmonary accumulation of 131-MIBG studied in an isolated perfused rat lung model. J Nucl Med 133:1076, A664
Slosman DO, Brill AB, Polla BS, Alderson PO (1987) Evaluation of [iodine125]N,N,N,′-trimethyl-N′-[2-hydroxy-3-methyl-5-iodobenzyl]-1,3-propanediamine lung uptake using an isolated perfused rat lung. J Nucl Med 28:203–208
Slosman DO, Davidson D, Brill AB, Alderson PO (1988a)131Imeta-iodo-benzylgluanidine uptake in the isolated perfused rat lung: a potential marker of endothelial cell function. Eur J Nucl Med 13:543–547
Slosman DO, Morel DR, Mo Costabella P, Suter PM, Donath A (1988b) Lung uptake of 131-metaiodobenzylguanidine in sheep. An in-vivo measurement of pulmonary metabolic function. Eur J Nucl Med 14:65–70
Slosman DO, Morel DR, Alderson PO (1988c) A new imaging approach to quantitative evaluation of pulmonary vascular endothelial metabolism. J Thorac Imag 3:49–52
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Slosman, D.O., Polla, B.S. & Donath, A. 123I-MIBG pulmonary removal: a biochemical marker of minimal lung endothelial cell lesions. Eur J Nucl Med 16, 633–637 (1990). https://doi.org/10.1007/BF00998161
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00998161