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Development of a Real-Time Polymerase Chain Reaction Assay for Prediction of the Uptake of Meta-[¹³¹I]iodobenzylguanidine by Neuroblastoma Tumors¹

Departments of Radiation Oncology and Child Health, University of Glasgow, Cancer Research UK Beatson Laboratories, Glasgow G61 1BD, United Kingdom [S. C., R. J. M., A. G. M.]; Department of Child Health, Royal Victoria Infirmary and University of Newcastle, Newcastle upon Tyne NE1 4LP, United Kingdom [D. A. T., A. D. J. P.]; Cancer Research Unit, The Medical School, University of Newcastle, Newcastle NE2 4HH, United Kingdom [D. A. T., R. E. G., A. D. J. P., J. L.]; Department of Radiology, Sheffield Children’s Hospital NHS Trust, Sheffield S10 2TH, United Kingdom [A. S., C. Es., J. B., R. E. G.]; United Kingdom Children’s Cancer Study Group, Department of Epidemiology and Public Health, University of Leicester, Leicester LE1 6TP, United Kingdom [C. El.]; Pediatric Oncology Research Laboratory, G. Gaslini Institute, 16148 Genoa, Italy [P. G. M., M. P.]; Department of Nuclear Medicine, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands [C. A. H.]; and Departments of Nuclear Medicine [B. L. v. E-S.] and Pediatric Oncology [M. v. d. B., G. A. M. T., H. N. C.], Academical Medical Center, University of Amsterdam, 1100 DD Amsterdam, the Netherlands

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.

Experimental Design: Tumor specimens from 54 neuroblastoma patients were analyzed using real-time PCR, and NAT expression was compared with the corresponding diagnostic scintigrams.

Results: Forty-eight of 54 (89%) of tumors showed MIBG uptake by scintigraphy. NAT expression was found to be significantly associated with MIBG uptake (P < 0.0001, Fisher’s exact test). None of the samples from the six tumors that failed to concentrate MIBG expressed detectable levels of the NAT (specificity = 1.0). However, of the 48 MIBG uptake-positive tumors, only 43 (90%) expressed NAT (sensitivity = 0.9). The real-time PCR test has a positive predictive value of 1.0 but a negative predictive value of 0.55.

Conclusions: The results indicate that whereas this method has substantial ability to predict the capacity of neuroblastoma tumors to accumulate MIBG, confirmation is required in prospective studies to determine more accurately the predictive strength of the test and its role in the management of patients with neuroblastoma.

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