title: Assessment of anthracycline-related myocardial adrenergic derangement by [123I]metaiodobenzylguanidine scintigraphy.
abstract: Myocardial adrenergic neuron integrity and function were evaluated in 21 patients who had received doxorubicin or epirubicin for various malignancies. Myocardial uptake of iodine-123 metaiodobenzylguanidine ([123I]MIBG), a marker suitable for the study of myocardial neuron injury, was calculated from planar scintigraphic images after 4 h and the washout between 15 min and 4 h. In 13 patients with normal left ventricle ejection fraction (LVEF) analysed at three cumulative dose levels (no, low and middle dose), [123I]MIBG uptake tended to be significantly impaired (z = -2.772, P = 0.0056), at higher cumulative dose levels, before significant LVEF changes were observed. [123I]MIBG values were considerably decreased in 2/7 patients investigated at low cumulative dose and in 3/8 cases at the middle dose level. On follow-up, 1 of these patients, who had normal LVEF after completion of chemotherapy but whose [123I]MIBG values had progressively deteriorated during anthracycline therapy, subsequently developed congestive heart failure; another patient, whose [123I]MIBG values were impaired at the middle dose level, developed persistent reduced LVEF 5 months after completing therapy. In 8 patients, who had developed persistently, reduced LVEF at high doxorubicin cumulative dose levels, [123I]MIBG, performed in the period after chemotherapy discontinuation, was invariably abnormal. These data suggest that myocardial adrenergic derangement plays a role in anthracycline-associated cardiotoxicity: its appearance, even at low cumulative anthracycline dose levels, may reflect impairment of the intravesicular norepinephrine storage by incipient anthracycline-associated cardiac neuron injury. [123I]MIBG scintigraphy may be useful to assess myocardial adrenergic derangement during and in the follow-up of anthracycline therapy and potentially detect patients who are at risk.
authors.affiliation: Dept. of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam.
authors.forename: R A
authors.initials: RA
authors.lastname: Valdés Olmos
authors.forename: W W
authors.initials: WW
authors.lastname: ten Bokkel Huinink
authors.forename: R F
authors.initials: RF
authors.lastname: ten Hoeve
authors.forename: H
authors.initials: H
authors.lastname: van Tinteren
authors.forename: P F
authors.initials: PF
authors.lastname: Bruning
authors.forename: B
authors.initials: B
authors.lastname: van Vlies
authors.forename: C A
authors.initials: CA
authors.lastname: Hoefnagel
mesh_terms: D019797:3-Iodobenzylguanidine; D000320:Adrenergic Fibers / Q000000981:diagnostic imaging / Q000187:drug effects*; D000328:Adult; D004317:Doxorubicin / Q000009:adverse effects*; D015251:Epirubicin / Q000009:adverse effects*; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000294:innervation*; D006801:Humans; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy; D011877:Radionuclide Imaging; D013318:Stroke Volume
chemical_list: D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D019797:3-Iodobenzylguanidine; D015251:Epirubicin; D004317:Doxorubicin