Evaluation of Tc99m-glucoheptonate for SPECT functional imaging of medulloblastoma

Barai, Sukanta; Bandopadhayaya, G. P.; Julka, Pramod Kumar; Kale, Shashank S.; Kumar, Rakesh; Malhotra, Arun; Haloi, A. K.; Seith, A.; Naik, K. K.; Halanaik, Dhanapathi

doi:10.1016/j.jocn.2004.02.015

Cited by 11 publications

(9 citation statements)

References 13 publications

(13 reference statements)

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“…Moreover, the overall reduction in Abcg2 expression in tumor samples post-treatment suggests the treatment of topotecan and Ko143 eradicates medulloblastoma expressing Abcg2. While these findings suggests this combination therapy is efficacious, it is unknown if this would be effective in the treatment of brain tumors because it is unclear whether the integrity of the BBB is disrupted in all children with medulloblastoma (41). Indeed, recent data suggest that the structure and function of the BBB varies markedly among the various subtypes of medulloblastoma (Richard Gilbertson, personal communication).…”

Section: Discussionmentioning

confidence: 99%

ABCG2 Transporter Expression Impacts Group 3 Medulloblastoma Response to Chemotherapy

et al. 2015

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While a small number of plasma membrane ABC transporters can export chemotherapeutic drugs and confer drug resistance, it is unknown if these transporters are expressed or functional in less therapeutically tractable cancers such as Group3 medulloblastoma (G3 MB). Herein we show that among this class of drug transporters only ABCG2 was expressed at highly increased levels in human G3 MB and a mouse model of this disease. In the mouse model, Abcg2 protein was expressed at the plasma membrane where it functioned as expected based on export of prototypical substrates. By screening ABC substrates against mouse G3 MB tumorspheres in vitro, we found that Abcg2 inhibition could potentiate responses to the clinically employed drug topotecan, producing a >9-fold suppression cell proliferation. Extended studies in vivo in this model confirmed that Abcg2 inhibition was sufficient to enhance antiproliferative responses to topotecan, producing a significant survival advantage compared to subjects treated with topotecan alone. Our findings offer a preclinical proof of concept for blockade of ABCG2 transporter activity as a strategy to empower chemotherapeutic responses in Group3 medulloblastoma.

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Section: Discussionmentioning

confidence: 99%

ABCG2 Transporter Expression Impacts Group 3 Medulloblastoma Response to Chemotherapy

et al. 2015

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“…In this intracranial transplant model, the BBB was clearly compromised. However, it is unclear whether the integrity of the BBB is disrupted in children with MB, which would facilitate brain penetration (38, 39). Other strategies to achieve direct delivery to tumors might be considered including continuous infusion of tiny LNAs into the ventricles using minipumps (40) or the use of nanoparticles.…”

Section: Discussionmentioning

confidence: 99%

Silencing of the miR-17∼92 Cluster Family Inhibits Medulloblastoma Progression

et al. 2013

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Medulloblastoma (MB), originating in the cerebellum, is the most common malignant brain tumor in children. MB consists of four major groups where constitutive activation of the Sonic Hedgehog (SHH) signaling pathway is a hallmark of one group. Mouse and human SHH MBs exhibit increased expression of microRNAs encoded by the miR-17~92 and miR-106b~25 clusters compared to granule progenitors and post-mitotic granule neurons. Here, we assessed the therapeutic potential of 8-mer seed-targeting LNA-modified antimiR oligonucleotides, termed tiny LNAs, that inhibit microRNA seed families expressed by miR-17~92 and miR-106b~25 in two mouse models of SHH MB. We found that tumor cells (MB cells) passively took up 8-mer LNA-antimiRs, and specifically inhibited targeted microRNA seed-sharing family members. Inhibition of miR-17 and miR-19a seed families by antimiR-17 and antimiR-19, respectively, resulted in diminished tumor cell proliferation in vitro. Treatment of mice with systemic delivery of antimiR-17 and antimiR-19 reduced tumor growth in flank and brain allografts in vivo and prolonged the survival of mice with intracranial transplants, suggesting that inhibition of the miR-17~92 cluster family by 8-mer LNA-antimiRs might be considered for the treatment of SHH MBs.

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“…MRI is usually used for the initial diagnosis of the brain tumor. Tc-99m-labeled glucoheptonate (GHA) and Tc-99m-labeled methoxyisobutylisonitrile have shown a definitive role for the assessment of the recurrence of the tumor [4,5]. Many studies have been published showing the role of PET (using different markers) in brain tumors for making their diagnosis, performing preoperative …”

Section: Cns Tumorsmentioning

confidence: 99%

“…PET, PET/CT in pediatric malignancies assessment and to find out the residual and/or recurrent tumor (Table 1) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. The role of FDG PET has been well established in differentiating viable tumor and postoperative changes in adults [6][7][8].…”

Section: Reviewmentioning

confidence: 99%

Clinical applications of PET and PET/CT in pediatric malignancies

Kumar

Shandal

Shamim

et al. 2010

Expert Review of Anticancer Therapy

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The common childhood cancers are leukemia, CNS tumors, lymphomas, soft-tissue tumors (such as rhabdomyosarcoma and fibrosarcoma), neuroblastoma, malignant bone tumors, germ cell tumors with neoplasms of gonads and hepatic tumors. Usually the conventional imaging modalities, such as x-ray, ultrasound, computed tomography (CT) and MRI, are being routinely used for the management of these pediatric malignancies. However, most of these modalities provide structural information and are lacking in functional/metabolic status of these malignancies. Recently, PET and PET/CT have emerged as a functional diagnostic imaging modality for the management of various cancers in adult population. Up to now most of the data published in the literature are on PET alone. PET used in conjunction with CT is useful as it provides an enhanced view of the anatomical details and the malignant focus then can be located with highest accuracy. PET and PET/CT has been found to be useful in, for example, CNS tumors, lymphomas, soft-tissue tumors, neuroblastoma, malignant bone tumors and germ cell tumors. PET/CT has a limited role in early diagnosis, however, it plays an important role in initial staging, treatment response evaluation and detection of metastatic disease in these cancers. Despite the fact that PET/CT has better diagnostic value when compared with conventional imaging, such as CT and MRI, in the management of many pediatric cancers, there are certain limitations. PET/CT has a limited role in detection of lesions smaller than 5 mm, well-differentiated tumors and tumors with low metabolic rate. Many infections and inflammation can lead to false-positive PET/CT results. In the present review we will discuss the various clinical indications of PET and PET/CT in pediatric cancers.

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Evaluation of Tc99m-glucoheptonate for SPECT functional imaging of medulloblastoma

Cited by 11 publications

References 13 publications

ABCG2 Transporter Expression Impacts Group 3 Medulloblastoma Response to Chemotherapy

ABCG2 Transporter Expression Impacts Group 3 Medulloblastoma Response to Chemotherapy

Silencing of the miR-17∼92 Cluster Family Inhibits Medulloblastoma Progression

Clinical applications of PET and PET/CT in pediatric malignancies

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