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  • Title: Meta-[123I]iodobenzylguanidine is selectively radiotoxic to neuroblastoma cells at concentrations that spare cells of haematopoietic lineage.
    Author: He Y, Das B, Baruchel S, Kumar P, Wiebe L, Reilly RM.
    Journal: Nucl Med Commun; 2004 Nov; 25(11):1125-30. PubMed ID: 15577592.
    Abstract:
    BACKGROUND: The Auger electron-emitting agents meta-[125I]iodobenzylguanidine (125I-MIBG) and 123I-MIBG have been proposed as alternatives to 131I-MIBG for the treatment of neuroblastoma, due to the absence of a cross-fire effect which may minimize bone marrow toxicity. However, the differential toxicity of 123I-MIBG towards neuroblastoma cells and cells of haematopoietic lineage has not been studied. OBJECTIVE: To compare the toxic effects of 123I-MIBG on SK-N-SH and SK-N-BE(2) neuroblastoma cells and on cells of haematopoietic lineage, specifically HL-60 human myeloid leukemia cells and bone marrow stem cells (BMSCs) from human adult donors. METHODS: The antiproliferative effects of exchange-labelled or no carrier added (n.c.a.) 123I-MIBG, unlabelled MIBG or the trimethylsilylbenzylguanidine (MTBG) precursor used to prepare n.c.a. 123I-MIBG against SK-N-SH or SK-N-BE(2) cells or HL-60 cells were evaluated using a cell proliferation assay. The toxicity of 123I-MIBG towards SK-N-SH cells or BMSCs from healthy adult human donors was studied using a clonogenic assay. RESULTS: 123I-MIBG was strongly growth inhibitory to SK-N-SH or SK-N-BE(2) cells at concentrations (IC50 185-370 mBq.ml(-1); IC90 740 mBq.ml(-1)) that were sparing to HL-60 cells. Treatment of SK-N-SH cells with 74 mBq of 123I-MIBG decreased colony formation by >90%, whereas colonies from all three populations of stem cells were formed at amounts up to 370 mBq. It was discovered that the MTBG precursor was non-specifically toxic towards both SK-N-SH cells and HL-60 cells, suggesting the need to purify n.c.a. 123I-MIBG for clinical use. CONCLUSION: Our results suggest that 123I-MIBG is a promising novel radiotherapeutic agent for neuroblastoma. For the first time, we report that the MTBG precursor used to prepare n.c.a. 123I-MIBG was toxic towards neuroblastoma cells as well as to HL-60 cells, representing cells of the haematopoietic lineage, suggesting the need for purification.
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