Radiopharmaceutical model using99mTc-MIBI to evaluate amifostine protection against doxorubicin cardiotoxicity in rats

Abstract

The aim of our study was to use an in vivo radiopharmaceutical model to investigate the cytoprotective effect of amifostine against doxorubicin-induced cardiotoxicity. Male Wistar rats were randomly divided into four groups (n = 6): 1) Saline (control); 2) Doxorubicin (DOX; 10 mg/ kg(-l) intraperitoneally); 3) Amifostine (AMI; 200 mg/kg(-1) intraperitoneally); 4) Doxorubicin plus amifostine (DOX + AMI). Amifostine was injected 30 minutes before doxorubicin in Group 4. 99mTc-MIBI, 20 MBq/0.2 ml(-1), was injected through the tail vein 72 hours after the drug administration. Rats were killed and samples of myocardium were removed by dissection 60 minutes after the injection of radiopharmaceutical. Radioactivity in each organ sample was counted using a Cd(Te) detector equipped with RAD 501 single-channel analyzer. The percent radioactivity was expressed as a percentage of the injected dose per gram of tissue (%ID/g(-1)). The %ID/g(-1) activity was calculated by dividing the activity in each sample by the total activity injected and mass of each organ. 99mTc-MIBI uptake as %ID/g(-1) was 1.194 +/- 0.502 and 0.980 +/- 0.199 in the control and AMI groups, respectively. Doxorubicin administration resulted in a significant increase in %ID/ g(-1) (3.285 +/- 0.839) (p < 0.05). Amifostine administration 30 minutes before doxorubicin injection resulted a significant decrease in %ID/g(-1) (2.160 +/- 0.791) (p < 0.05) compared with doxorubicin alone. The results showed that amifostine significantly attenuated doxorubicin-induced cardiotoxicity.

Whole body vibration exercise combined with an extract ofCoriandrum sativummodify some biochemical/physiological parameters in rats

“…One of the possible ways to study these vibrations in tissues/organs, it is by evaluating the biodistribution of radiopharmaceuticals, as already described for physical activity [19], chemical [20], and physical (laser) agents [21]. Pereira et al [22] (vibration with 20 Hz) and Frederico et al [16] (vibration with 12 Hz) reported the effect of WBV exercise in the biodistribution of radiopharmaceuticals in rats using a side-alternating platform.…”

Decreased Myocardial Tl-201 Uptake in Rats: Early Sign of Doxorubicin Induced Myocardial Damage and the Relation to Inflammation

“…In one study, the authors evaluated the kinetics of 99mTc-MIBI in DOX-treated cultured chick heart cells (7) and they found a decreased accumulation of 99mTc-MIBI in the cells. Contrary to this findings, Yürekli et al (8) found an increase in the cardiac uptake of 99mTc-MIBI in the DOX-induced acute cardiac injury in a in vivo model. In another study, where chronic cardiac injury assesed with 201 Tl which has a different kinetic than 99mTc-MIBI and show redistribution (9), it was found that T1-201 uptake after 180 minutes increased with the progression of histological score (9).…”

“…In order to elucidate the cellular and metabolic changes before the development of the functional disorders, numerous studies have been conducted on a serial of molecular cardiac imaging agents (2). Although the agents like 99mTc-MIBI (methoxyisobutyl isonitrile) and 201Tl (6), which can indicate the myocardial perfusion as well as the cellular integrity successfully revealed the DOX damage, the data concerning the myocard perfusion agents is very limited and uptake mechanisms are not known exactly (7)(8)(9). DOX-induced cardiac injury presents classical findings such as vacuolization in the cytoplasm, myofibrillar degeneration and necrosis under the light microscopy, as well as myocardial inflammation which is another pathological finding that shows inflammatory cell infiltration itself under the light microscopy and is associated with the injury, but can be seen in isolation (4,(10)(11)(12).…”

The effect of applied cytotoxic drugs on biological behaviour of 99mTc-radiopharmaceuticals

“…Takođe je poznato da mnogi lekovi utiču na raspoređivanje radiofarmaceutskog leka u organizmu, povećavanje njegovog nakupljanja u kritičnom organu, ali i u drugim organima, i samim tim povećava se i efektivna doza [4][5][6]. Takođe je poznato da mnogi lekovi utiču na raspoređivanje radiofarmaceutskog leka u organizmu, povećavanje njegovog nakupljanja u kritičnom organu, ali i u drugim organima, i samim tim povećava se i efektivna doza [4][5][6].…”