Activity of iodine-123 metaiodobenzylguanidine in childhood neuroblastoma: lack of relation to tumour differentiation in vivo

Abstract

Neuroblastoma (NB) tumour cells have a remarkable tendency to differentiate spontaneously or under the influence of certain drugs. It is not clear whether metaiodobenzylguanidine (MIBG) uptake correlates with differentiation of NB cells. In 28 tumours of 26 patients, iodine-123 MIBG uptake in primary NBs was studied in relation to tumour differentiation, tumour size, cell density and degree of necrosis in subsequently resected specimens. Genetic features such as the presence of chromosomal aberrations (1p-deletion and MYCN amplification) and/or P-glycoprotein (mdr-1 gene product) were also evaluated in relation to MIBG uptake. A highly variable and unpredictable intensity of MIBG uptake was observed in primary as well as secondary resected tumours. This intensity did not relate to any of the above-mentioned factors except that there was a trend towards more intense uptake with increasing size of the tumour. We conclude from our observations that, in contrast to commonly held opinion, well-differentiated tumours do not a priori show a lower MIBG uptake in vivo, even when there are a low number of viable cells and a high degree of necrosis. The degree of differentiation or tumour viability and necrosis following longstanding chemotherapeutic treatment cannot be predicted by the MIBG scan findings. The observed MIBG uptake may be importantly influenced by factors other than those associated with cellular differentiation.

Evaluation of Norepinephrine Transporter Expression and Metaiodobenzylguanidine Avidity in Neuroblastoma: A Report from the Children's Oncology Group

“…As an exploratory secondary analysis unadjusted for multiple statistical testing, it is also possible that this association is a chance finding and therefore requires replication by other groups. We note that one previous report did not detect a difference in clinical MIBG avidity according to tumor MYCN status [31]. In addition, response rates after high-dose 131 I-MIBG therapy do not appear to differ between patients with MYCN amplified and MYCN nonamplified tumors, though all patients were required to have MIBG avid tumors to receive 131 I-MIBG therapy [32].…”

A Phase I Clinical Trial of the hu14.18-IL2 (EMD 273063) as a Treatment for Children with Refractory or Recurrent Neuroblastoma and Melanoma: a Study of the Children's Oncology Group

“…It should be noted, however, that the disappearance of MIBG is possible in patients with neuroblastoma even without intervention. Late disappearance of MIBG can be observed due to loss of MIBG avidity by the tumor, as well as technical factors that can modify MIBG uptake (21). At the time of study entry, this patient's bone marrow showed one neuroblastoma cell per 100,000 cells by immunocytochemistry.…”

Clinical experience with18F-fluorodeoxyglucose positron emission tomography and123I-metaiodobenzylguanine scintigraphy in pediatric neuroblastoma: complementary roles in follow-up of patients

“…MIBG is an analog of the adrenergic norepinephrine neurotransmitter, which is taken by the adrenergic origin of NBL and pheochromocytoma using the type 1 cathecolamine uptake mechanism for transport into tumor cells17). Uptake of 123 I-MIBG was highly variable in vivo, and probably influenced by multiple factors such as degree of differentiation in neuroendocrine tumor, interfering medication, and change in the metabolism of the malignant cells due to altered biology13,20). 18 F-FDG, similar to glucose, is transported to within the cells via the GULT (glucose transporters) and intracellular phosphorylated by hexokinase into glucose-6-phosphate and 18 F-FDG-6-phosphate.…”