Metaiodobenzylguanidine: evaluation of its potential as a tracer for monitoring doxorubicin cardiomyopathy.
We evaluated alterations in cardiac adrenergic neuron activity and progression of left ventricular dysfunction in comparison with the severity of structural changes using a rat model of adriamycin cardiomyopathy. Rats were treated with adriamycin (2 mg/kg s.c. once a week) for 6, 7, 8 and 9 wk. Accumulation of 125I-metaiodobenzylguanidine (MIBG) 4 hr after intravenous administration was determined and left ventricular ejection fraction (LVEF) was calculated from gated blood-pool images. H & E and Masson-Trichrome stained specimens of the myocardium were examined by light microscopy. Histopathologic examination demonstrated dose-dependent myocyte damage, although there were no differences between the 8-wk and 9-wk groups. LVEF did not differ between controls and the 6-wk group (81.3% +/- 5.5% versus 82.1% +/- 4.8%, p = ns). LVEF began to decrease slightly in the 7-wk group (75.0% +/- 5.7%, p < 0.05) and showed a remarkable decrease in the 8-wk group (53.7% +/- 2.6%, p < 0.001). In the 9-wk group, LVEF diminished to 47.9% +/- 3.1% (p < 0.001), accompanied by massive pleural effusions and ascites. MIBG accumulation in the heart (%ID/heart) significantly and progressively diminished; 1.42% +/- 0.15% in the 6-wk group, 1.06% +/- 0.16% in the 7-wk group, 0.77% +/- 0.13% in the 8-wk group and 0.34% +/- 0.11% in the 9-wk group, respectively p < 0.001, compared to controls (1.99% +/- 0.30%). These results demonstrate that MIBG accumulation in the heart showed a greater and more linear dose-dependent decrease than LVEF. Furthermore, MIBG uptake was significantly reduced in the 6-wk group where only mild myocyte damage (isolated vacuolation or myofibrillar loss) was observed. Thus, MIBG may be a sensitive biochemical marker of adriamycin cardiomyopathy.
Wakasugi
S
S
Department of Radiology, Massachusetts General Hospital, Boston 02114.
Fischman
A J
AJ
Babich
J W
JW
Aretz
H T
HT
Callahan
R J
RJ
Nakaki
M
M
Wilkinson
R
R
Strauss
H W
HW
D019797:3-Iodobenzylguanidine; D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced*; D003287:Contrast Media; D004317:Doxorubicin / Q000633:toxicity*; D016903:Drug Monitoring / Q000379:methods*; D005069:Evaluation Studies as Topic; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D003287:Contrast Media; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D019797:3-Iodobenzylguanidine; D004317:Doxorubicin