Preclinical assessment of strategies for enhancement of metaiodobenzylguanidine therapy of neuroendocrine tumors.

By virtue of its high affinity for the norepinephrine transporter (NET), [(131)I]metaiodobenzylguanidine ([(131)I]MIBG) has been used for the therapy of tumors of neuroectodermal origin for more than 25 years. Although not yet universally adopted, [(131)I]MIBG targeted radiotherapy remains a highly promising means of management of neuroblastoma, pheochromocytoma, and carcinoids. Appreciation of the mode of conveyance of [(131)I]MIBG into malignant cells and of factors that influence the activity of the uptake mechanism has indicated a variety of means of increasing the effectiveness of this type of treatment.

Optimizing MIBG therapy of neuroendocrine tumors: preclinical evidence of dose maximization and synergy.

[(131)I]meta-Iodobenzylguanidine ([(131)I]MIBG) has been used for the therapy of tumors of neuroectodermal origin since the 1980s. Its role in the management of these malignancies remains controversial because of the large variation in response rates. Appreciation of the mode of conveyance of [(131)I]MIBG via the noradrenaline transporter into malignant cells and of factors that influence the activity of the uptake mechanism has indicated various ways in which the effectiveness of this type of targeted radiotherapy may be improved.

Feasibility of dosimetry-based high-dose 131I-meta-iodobenzylguanidine with topotecan as a radiosensitizer in children with metastatic neuroblastoma.

Introduction: (131)I-meta iodobenzylguanidine ((131)I-mIBG) therapy is established palliation for relapsed neuroblastoma. The topoisomerase-1 inhibitor, topotecan, has direct activity against neuroblastoma and acts as a radiation sensitiser. These 2 treatments are synergistic in laboratory studies.

Development of a real-time polymerase chain reaction assay for prediction of the uptake of meta-[(131)I]iodobenzylguanidine by neuroblastoma tumors.

Purpose: The suitability of neuroblastoma patients for therapy using radiolabeled meta-iodobenzylguanidine (MIBG) is determined by scintigraphy after the administration of a tracer dose of radioiodinated MIBG whose uptake is dependent upon the cellular expression of the noradrenaline transporter (NAT). As a possible alternative to gamma camera imaging, we developed a novel molecular assay of NAT expression. mRNA extracted from neuroblastoma biopsy samples, obtained retrospectively, was reverse transcribed, and NAT-specific cDNA was quantified by real-time PCR, referenced against the expression of the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase.