Exploiting the MIBG-avidity of neuroblastoma for staging and treatment

Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Pediatric Blood & Cancer (Impact Factor: 2.39). 12/2006; 47(7):863-4. DOI: 10.1002/pbc.20821
Source: PubMed
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    ABSTRACT: Both [(131)I]meta-iodobenzylguanidine ([(131)I]MIBG) and the topoisomerase I inhibitor topotecan are effective as single-agent treatments of neuroblastoma. The aim of this study was to investigate the efficacy of [(131)I]MIBG in combination with topotecan in vitro and in vivo. The cell lines used were SK-N-BE(2c) (human neuroblastoma) and UVW/NAT (glioma cell line transfected with the noradrenaline transporter gene). Three different treatment schedules were assessed: topotecan given before (schedule 1), after (schedule 2), or simultaneously (schedule 3) with [(131)I]MIBG. DNA strand breakage was evaluated by comet assay, and cytotoxicity was determined by clonogenic survival. Efficacy was also measured by growth delay of tumor xenografts in nude mice. Combination schedules 2 and 3 caused more cytotoxicity than schedule 1. Similarly, significant DNA damage was observed following treatment schedules 2 and 3 (P < 0.005) but not schedule 1. The mean number of days for a doubling in volume of SK-N-BE(2c) tumors and a 10-fold increase in volume of UVW/NAT tumors were 10.4 and 18.6 (untreated), 19.7 and 25.3 (topotecan alone), 22.8 and 31.9 ([(131)I]MIBG alone), 26.3 and 37.1 (combination schedule 1), 34.3 and 49.7 (combination schedule 2), and 53.2 and >71 (combination schedule 3), respectively. The highest rate of cure of both xenografts was observed following treatment with combination schedule 3. The combination of topotecan and [(131)I]MIBG compared with either treatment alone gave rise to greater than additive DNA damage, clonogenic cell kill, and tumor growth delay. These effects were dependent on the scheduling of the two agents.
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    ABSTRACT: A new semi-quantitative scoring system is proposed, especially designed for the comparative interpretation of sequential whole-body meta-iodo-benzyl-guanidine (MIBG) scans in stage IV neuroblastoma children. This method was applied to assess whether MIBG scan at mid-course of induction chemotherapy could predict the final response. 27 newly diagnosed children were investigated by three sequential 123I-MIBG scans performed at the beginning, at mid-course (6 weeks) and at the end of neoadjuvant chemotherapy (12 weeks). Whole body scans were divided into nine regions in which the extension of bone metastases was separately quoted (score range: 0-3). The overall absolute scores were obtained by adding the scores of the nine regions. Relative scores were calculated by dividing the absolute score at each time by the corresponding pretreatment score. The score at mid-induction correctly predicted the overall response of metastases at the end of induction (P < 0.0001) in most cases. This method is easy to use, reproducible, subject to little inter-investigator variation, and thus well adapted to multicentric trials.
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    ABSTRACT: In pediatrics, the distribution of radioiodinated metaiodobenzylguanidine (MIBG) has been studied primarily in neuroblastoma. However, normal patterns in children show a number of particularities and pitfalls related to the context of pediatric oncology which must be identified. We report on 28 equivocal scans in 24 children. In all cases, two experienced observers judged the scans to be equivocal and the definite interpretations were confirmed by follow-up. Difficulties in interpreting the scans were observed at the level of the thorax (15 patients), the abdomen (5 patients), the head (4 patients) or elsewhere (4 patients). The final interpretation of the scans was attributed to an unusual physiological pattern linked to age (9 patients), tumoral context (17 patients) or artifacts (2 patients). A number of important physiological areas of uptake in soft tissues can lead to false-positive interpretations of normal scans, such as the physiological upper thoracic uptake which has never been previously described. Numerous technical and physiological possibilities exist and those pitfalls must be ruled out. A precise knowledge of these technical difficulties and physiological variants can reduce the number of equivocal MIBG scans.
    Journal of Nuclear Medicine 06/1994; 35(5):803-10. · 6.16 Impact Factor
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