In this study, we investigated prospectively the diagnostic role of Tc-99(m)-MIBI for staging and for predicting the therapeutic response of stage nr neuroblastoma compared wth I-131-MIBG imaging and Tc-99(m)- MDP bone scintigraphy. Nine patients (4 girls and 5 boys aged 1-7 years) with suspected or proven stage IV neuroblastoma were studied with Tc-99(m)-MIBI at initial diagnosis and after 12-18 months of multidrug therapy. After the injection of 80 MBq.kg(-1) Tc-99(m)-MIBI, early (10 min) and delayed (1 h) images were obtained. The data were correlated with I-131-MIBG scans, bone scintigraphy, ultrasound, computed tomography and/or magnetic resonance imaging, and bone marrow biopsy. Eight of nine primary tumours and 41 metastatic lesions were detected by I-131-MIBG scintigraphy. None of the primary lesions demonstrated significant Tc-99(m)-MIBI accumulation. Sestamibi was positive in 16 of 41 MIBG-avid metastatic lesions. After six courses of multidrug chemotherapy, 30 I-131-MIBG-avid neuroblastoma metastases that were Tc-99(m)-MIBI-negative at the time of diagnosis still did not show significant sestamibi accumulation. Follow-up demonstrated that all lesions that were Tc-99(m)-MIBI-avid at the time of diagnosis remained negative. Of these 16 lesions, seven were positive for I-131-MIBG accumulation with no reduction in size, and nine showed resolution after therapy. New metastatic foci detected by MIBG scintigraphy did not accumulate Tc-99(m)-MIBI. Clinical evaluation of patients with no Tc-99(m)-MIBI uptake in primary and secondary sites of neuroblastoma confirmed that they were resistant to multidrug chemotherapy. AII Tc-99(m)-MIBI-positive lesions, irrespective of clinical outcome, demonstrated significant clearance of tracer on the delayed images. We conclude that Tc-99(m)-MIBI has no role in the staging of neuroblastoma. Sestamibi is a well-documented transport substrate for P-glycoprotein-related multidrug resistance and serial imaging may provide prognostic information on the therapeutic value of chemotherapy. ((C) 1999 Lippincott Williams & Wilkins).