Meta-[123I]iodobenzylguanidine is selectively radiotoxic to neuroblastoma cells at concentrations that spare cells of haematopoietic lineage.
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.


CONCLUSIONS
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.
He
Ying
Y
Division of Nuclear Medicine, University Health Network, Toronto, Canada.
Das
Bikul
B
Baruchel
Sylvain
S
Kumar
Piyush
P
Wiebe
Leonard
L
Reilly
Raymond M
RM
D019797:3-Iodobenzylguanidine / Q000008:administration & dosage* / Q000009:adverse effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006412:Hematopoietic Stem Cells / Q000473:pathology* / Q000528:radiation effects*; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology* / Q000532:radiotherapy*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine