TY - JOUR
T1 - Development of a real-time polymerase chain reaction assay for prediction of the uptake of meta-[131I]iodobenzylguanidine by neuroblastoma tumors
AU - Carlin, Sean
AU - Mairs, Rob J.
AU - McCluskey, Anthony G.
AU - Tweddle, Deborah A.
AU - Sprigg, Alan
AU - Estlin, Christine
AU - Board, Julian
AU - George, Rani E.
AU - Ellershaw, Caroline
AU - Pearson, Andrew D.J.
AU - Lunec, John
AU - Montaldo, Paolo G.
AU - Ponzoni, Mirco
AU - Van Eck-Smit, Berthe L.
AU - Hoefnagel, Cees A.
AU - Van Den Brug, Marieke D.
AU - Tytgat, Godelieve A.M.
AU - Caron, Huib N.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=10744226010&partnerID=8YFLogxK
M3 - Article
C2 - 12960120
AN - SCOPUS:10744226010
SN - 1078-0432
VL - 9
SP - 3338
EP - 3344
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 9
ER -