Somatostatin receptor scintigraphy in surveillance of pediatric brain malignancies

Department of Radiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Pediatric Blood & Cancer (Impact Factor: 2.39). 03/2008; 50(3):561-6. DOI: 10.1002/pbc.21194
Source: PubMed


Somatostatin receptor scintigraphy (SRS) has been successfully used in imaging PBTs and, as a functional imaging modality, may be better able to differentiate tumor from scar/necrosis. This retrospective study evaluates the role of SRS in post-treatment surveillance of PBTs.
Twenty children (age range: 7 months to 24 years, mean: 9 years) with known brain malignancies underwent serial SRS and MRI. The sensitivity and specificity of SRS and MRI were compared for surveillance scanning using patient outcome as the reference standard. Somatostatin receptors (sstrs) expression was determined by immunohistochemistry (IHC) of available tumor specimens.
SRS was true positive (TP) in 15 of 16 patients with proven disease found post-resection (n = 5) or during follow-up (n = 11). In contrast, MRI was positive in 12 of these 16 patients and equivocal in another two patients where it could not distinguish between radiation necrosis and tumor recurrence. The two patients with false negative (FN) MRI and proven disease were positive by SRS. SRS was negative in all four patients with no evidence of disease by follow-up (mean follow-up = 58 months). The only patient with a FN SRS (TP by MRI) was one without IHC evidence of sstrs. SRS was TP in 7/7 tumors with IHC documented sstrs.
SRS is a useful adjunct to MRI for post-treatment surveillance of sstr-positive PBTs, particularly when MRI is equivocal.

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    • "In regard to medulloblastoma, the ability to cross the blood–brain barrier is also crucial. 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]. "
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    ABSTRACT: Medulloblastoma is the most common malignant brain tumor in children. Genetic profiling has identified four principle tumor subgroups; each subgroup is characterized by different initiating mutations, genetic and clinical profiles, and prognoses. The two most well-defined subgroups are caused by overactive signaling in the WNT and SHH mitogenic pathways; less is understood about Groups 3 and 4 medulloblastoma. Identification of tumor subgroup using molecular classification is set to become an important component of medulloblastoma diagnosis and staging, and will likely guide therapeutic options. However, thus far, few druggable targets have emerged. G-protein coupled receptors (GPCRs) possess characteristics that make them ideal targets for molecular imaging and therapeutics; drugs targeting GPCRs account for 30-40% of all current pharmaceuticals. While expression patterns of many proteins in human medulloblastoma subgroups have been discerned, the expression pattern of GPCRs in medulloblastoma has not been investigated. We hypothesized that analysis of GPCR expression would identify clear subsets of medulloblastoma and suggest distinct GPCRs that might serve as molecular targets for both imaging and therapy. Our study found that medulloblastoma tumors fall into distinct clusters based solely on GPCR expression patterns. Normal cerebellum clustered separately from the tumor samples. Further, two of the tumor clusters correspond with high fidelity to the WNT and SHH subgroups of medulloblastoma. Distinct over-expressed GPCRs emerge; for example, LGR5 and GPR64 are significantly and uniquely over-expressed in the WNT subgroup of tumors, while PTGER4 is over-expressed in the SHH subgroup. Uniquely under-expressed GPCRs were also observed. Our key findings were independently validated using a large international dataset. Our results identify GPCRs with potential to act as imaging and therapeutic targets. Elucidating tumorigenic pathways is a secondary benefit to identifying differential GPCR expression patterns in medulloblastoma tumors.
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