Combining anatomic and molecularly targeted imaging in the diagnosis and surveillance of embryonal tumors of the nervous and endocrine systems in children

Abstract

Combining anatomical and functional imaging can improve sensitivity and accuracy of tumor diagnosis and surveillance of pediatric malignancies. MRI is the state-of-the-art modality for demonstrating the anatomical location of brain tumors with contrast enhancement adding additional information regarding whether the tumor is neuronal or glial. Addition of SPECT imaging using a peptide that targets the somatostatin receptor (Octreoscan) can now differentiate medulloblastoma from a cerebellar pilocytic astrocytoma. Combined MRI and Octreoscan is now the most sensitive and accurate imaging modality for differentiating recurrent medulloblastoma from scar tissue. CT is the most common imaging modality for demonstrating the anatomical location of tumors in the chest and abdomen. Addition of SPECT imaging with either MIBG or Octreoscan has been shown to add important diagnostic information on the nature of tumors in chest and abdomen and is often more sensitive than CT for identification of metastatic lesions in bone or liver. Combined anatomical and functional imaging is particularly helpful in neuroblastoma and in neuroendocrine tumors such as gastrinoma and carcinoid. Functional imaging with MIBG and Octreoscan is predictive of response to molecularly targeted therapy with 131I-MIBG and 90Y-DOTA-tyr3-Octreotide. Dosimetry using combined anatomical and functional imaging is being developed for patient-specific dosing of targeted radiotherapy and as an extremely sensitive monitor of response to therapy. Both MIBG and Octreotide are now being adapted to PET imaging which will greatly improve the utility of PET in medulloblastoma as well as increase the sensitivity for detection of metastatic lesions in neuroblastoma and neuroendocrine tumors.

Incidence, survival, and prevalence of neuroendocrine tumors versus neuroblastoma in children and young adults: Nine standard SEER registries, 1975–2006

“…The establishment of centers of care for children and young adults diagnosed with NETs is recommended with the expectation that earlier diagnosis utilizing multiple imaging modalities(31) and biochemical markers(32) coupled with targeted therapies and life-long follow-up, will decrease the incidence of metastatic disease and improve both quantity and quality of life for these young people. Given that adolescents and young adults have seen no improvement in cancer survival rates for decades(33), establishment of NET centers of care could also serve as a model for development of care guidelines to bridge the gap between pediatric oncology and adult oncology.…”

G-protein coupled receptor expression patterns delineate medulloblastoma subgroups

“…The utility of such a GPCR-targeted imaging modality has already been proven: The Octreoscan, which employs SPECT imaging to detect radiolabeled somatostatin receptor analogues has the ability to differentiate medulloblastoma from low-grade cerebellar tumors and provides an imaging modality to differentiate recurrent medulloblastoma from scar tissue, as well as to localize metastatic lesions [24,25,28]. Positron emission tomography (PET) imaging provides a higher degree of sensitivity than SPECT imaging [28] and somatostatin receptor targeted agents are being adapted for use with PET imaging [28]. Recent evidence has shown that high expression of somatostatin receptors, particularly in non-SHH subgroup tumors, is correlated to an increased survival and may have potential as a prognostic marker [36].…”

“…GPCRs possess characteristics that make them ideal targets for molecular imaging and therapeutics; including that they are membrane-bound, their ligands bind with high affinity and specificity, and that the receptor-ligand complex is subsequently endocytosed carrying the ligand into the tumor cell [23]. The utility of targeting GPCRs in medulloblastoma has been demonstrated with the advent of somatostatin receptor targeted imaging and therapy [24,25] and Octreoscans are now able to differentiate medulloblastoma from low-grade cerebellar tumors and scar tissue [25-28]. Molecularly targeted imaging has the potential to provide in vivo classification, and in vivo measurement of response to treatment as well as early detection of relapse.…”

G-protein coupled receptor expression patterns in medulloblastoma subgroups

“…However, PET provides images with substantially higher sensitivity and resolution than SPECT [155] and, as such, PET tracers probing the metabolic functions of neoplastic tissues are becoming more common-place. The use of 18 Ffluorodeoxyglucose (FDG) PET has already become the standard of care for assessment of treatment response in Hodgkin's disease, both for adults and children [138]. The use of FDG-PET in patients with medulloblastoma has been investigated and increased FDG uptake in tumor versus normal tissue was reported [61].…”

“…The use of FDG-PET in patients with medulloblastoma has been investigated and increased FDG uptake in tumor versus normal tissue was reported [61]. However, overall FDG-PET is of limited use for the imaging of brain tumors; the uniformly high utilization of glucose in the brain obscures any differentiation between normal and neoplastic tissue [138,181]. 18 F-fluorothymidine (FLT) is a newer PET tracer which probes the rate of DNA synthesis, thus exploiting the high proliferation rate of neoplastic tissues [138].…”