Evaluation of non‐respiratory function of the human lung by HIPDM lung scanning

Miniati, Massimo; Cocci, Franca; Paci, A; Giani, Luca

doi:10.1111/j.1475-097x.1992.tb00835.x

Cited by 3 publications

(5 citation statements)

References 16 publications

(13 reference statements)

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“…As shown by previous experiments on the metabolism of HIPDM, more than 90% of the radioactivity recovered from the lungs of rats and rabbits is in the form of unmetabolized compound [17,18]. By contrast, HIPDM is extensively metabolized in the liver [17,18]. The above findings are consistent with the observation that rat and rabbit lungs are devoid of diamine oxidase activity [34].…”

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 89%

“…The observation of an increased persistence of HIPDM in the lungs of smokers [20] and of patients with acute respiratory distress syndrome [18] may reflect some biochemical alteration of mitochondrial membranes that warrants further investigation. In this connection, it is worth considering that an unusual retention of the mitochondria-specific, fluorescent probe rhodamine 123 has been described in vitro in a variety of carcinoma cells [39], which express a significantly higher mitochondrial membrane potential as compared to normal epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it has been observed that HIPDM is cleared from the human lung at a slow exponential rate [20]. The pulmonary persistence of HIPDM is increased in asymptomatic smokers and in patients with acute respiratory distress syndrome (ARDS) as compared to healthy nonsmokers [18,20].…”

mentioning

confidence: 99%

“…As assessed in isolated perfused rat lungs, the pulmonary uptake of HIPDM is saturable, does not require an active transport system, and is competitively inhibited by other basic amines, such as imipramine, chlorpromazine and propranolol [16]. No significant in vivo metabolism of HIPDM has been detected in rat and rabbit lungs [17,18].…”

mentioning

confidence: 99%

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Mitochondria act as a reservoir for the basic amine HIPDM in the lung

Miniati¹,

Paci²,

Cocci³

et al. 1996

Eur Respir J

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M Mi it to oc ch ho on nd dr ri ia a a ac ct t a as s a a r re es se er rv vo oi ir r f fo or r t th he e b ba as si ic c a am mi in neIn the present study, we measured HIPDM lung kinetics and subcellular distribution in rabbits given i.v. 125 I-HIPDM. Rabbits were killed from 2 min to 5 h after injection, and the radioactivity retained in their lungs was measured. Subcellular lung fractions (nuclear, mitochondrial, lysosomal, microsomal, and postmicrosomal supernatant) were assayed for HIPDM radioactivity, protein content, and distribution of specific marker enzymes.HIPDM lung clearance in rabbits was nearly identical to that of humans. Virtually all the HIPDM radioactivity in lungs (98±1%) was associated with subcellular membranous structures. The highest HIPDM specific radioactivity was found in the mitochondrial fraction, and the subcellular distribution profile closely resembled that of the mitochondrial marker enzyme succinate cytochrome c reductase. No redistribution of HIPDM among subcellular compartments was observed over a 5 h period after injection.The data indicate that mitochondria act as reservoir for HIPDM in the lungs and contribute to the pulmonary persistence of this compound. HIPDM can be used to investigate the pulmonary uptake of basic amines in health and in lung disease.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Mitochondria act as a reservoir for the basic amine HIPDM in the lung

Miniati¹,

Paci²,

Cocci³

et al. 1996

Eur Respir J

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[123I]HIPDM pulmonary imaging demonstrates elastase-induced pullmonary emphysema

Shih¹,

Lai

Coupal

et al. 1993

Lung

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Because more than 90 percent of [123I]hydroxyiodobenzyl-propanediamine (HIPDM) is localized in the lung after intravenous injection, the radiopharmaceutical has been proposed as a lung imaging agent. Its potential usefulness for the detection of pulmonary emphysema was evaluated in an animal model of elastase-induced emphysema along with [99mTc]MAA lung perfusion imaging. To induce lung emphysema, Long-Evans rats (200-250 g) were given 400 IU/Kg elastase intratracheally under ether anesthesia. Four weeks after elastase treatment, 15 treated and 15 nontreated rats were paired and simultaneously imaged under a scintillation camera immediately following intravenous injection of 0.25-0.3 mCi[99mTc]MAA. The procedure was repeated 48 hr later using 0.25-0.3 mCi[123I]HIPDM. Activity in the region of interest (ROI) over the lungs was recorded after the injections. Total counts per ROI from each rat were measured and normalized by lung volume. The normalized lung activity ratio of treated/nontreated rats was computed. The mean ratios of HIPDM and MAA were 0.847 and 0.802, respectively. The significant decrease in uptake of both HIPDM (p < 0.021) and of MAA (p < 0.025) in the elastase-treated lungs indicates decrease in functioning vascular endothelium and decrease in number of pulmonary capillary vessels, respectively, reflecting damage in capillaries and small arterioles. The decrease in treated/nontreated ratios lung is consistent with a significant alteration in pulmonary function and a significant increase in mean linear intercept (p < 0.005) in treated lung. Since the imaging reflects pulmonary endothelial receptor function, [123I]HIPDM lung imaging may serve as an alternative diagnostic modality for pulmonary emphysema.

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