Indium-111-antimyosin and iodine-123-MIBG studies in early assessment of doxorubicin cardiotoxicity.
Detection of myocyte cell damage with 111In-antimyosin and impairment of adrenergic neuron function with [123I]MIBG during doxorubicin administration may provide easy identification of patients at risk of significant functional impairment.


METHODS
We studied 36 cancer patients who underwent chemotherapy, including doxorubicin, to assess [123I]MIBG and 111In-antimyosin uptake in the course of doxorubicin administration. MIBG scans, antimyosin scans and ejection fraction measurements were performed before chemotherapy, at intermediate cumulative doses and at maximal cumulative doses of doxorubicin. MIBG uptake was quantified by a heart-to-mediastinum ratio and antimyosin uptake was quantified by a heart-to-lung ratio.


RESULTS
All patients had absent antimyosin uptake (mean ratio 1.40 +/- 0.06) with normal MIBG uptake (ratio 1.85 +/- 0.29) before chemotherapy; ejection fraction was 61% +/- 8%. With a 240-300 mg/m2 dose of doxorubicin, an increase in antimyosin uptake was observed with a ratio of 1.85 +/- 0.2 (p < 0.01), whereas a similar degree of MIBG uptake was observed (mean ratio of 1.80 +/- 0.2, p = ns); ejection fraction was 59% +/- 5% (p = ns). At 420-600 mg/m2, increased antimyosin uptake was observed with a ratio of 2.02 +/- 0.3 (p < 0.01), and a decrease in MIBG uptake was also observed (mean ratio of 1.76 +/- 0.2, p < 0.05); ejection fraction was 52% +/- 8% (p < 0.05). Patients with more intense antimyosin uptake at intermediate doses tended to be those with more severe functional impairment at maximal cumulative doses.


CONCLUSIONS
At cumulative doses of 420-600 mg/m2, antimyosin and MIBG studies detect cell damage and impaired adrenergic neuron activity in patients with maintained or slightly decreased ejection fraction.
D019797:3-Iodobenzylguanidine; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000000981:diagnostic imaging*; D004317:Doxorubicin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D015637:Gated Blood-Pool Imaging; D006321:Heart / Q000000981:diagnostic imaging* / Q000294:innervation; D006801:Humans; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008297:Male; D009942:Organometallic Compounds; D012516:Osteosarcoma / Q000188:drug therapy; D012509:Sarcoma / Q000188:drug therapy; D013318:Stroke Volume / Q000187:drug effects; D013565:Sympatholytics; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D009942:Organometallic Compounds; D013565:Sympatholytics; D019797:3-Iodobenzylguanidine; C058899:imciromab pentetate; D004317:Doxorubicin