Preclinical Evaluation of no-Carrier-Added [131I]Meta-Iodobenzyl Guanidine, for the Treatment of Tumours Transfected with the Noradrenaline Transporter Gene

Boyd, Marie; Ross, Susan C.; Owens, Julie A.; Hunter, David G.; Babich, John W.; Zalutsky, Michael R.; Hamilton, Tom; Bell, Sandra; Mairs, Robert J.

doi:10.2174/1570180043485743

Cited by 16 publications

(11 citation statements)

References 1 publication

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“…OS was 49% at 1 year, but decreased to 29% at 2 years. 90 A phase I study of "no-carrier-added" 131 I-MIBG has recently been completed, showing acceptable toxicity and an ORR of 27%. Further evidence for the potential additional benefit of 131 I-MIBG therapy for adolescents and adults comes from a retrospective review that demonstrated an ORR of 46% in patients aged 10 years or older, with a trend toward better outcomes in those 18 years or older.…”

Section: I-mibg Therapymentioning

confidence: 99%

Current and Future Strategies for Relapsed Neuroblastoma

Morgenstern

Baruchel

Irwin

2013

Journal of Pediatric Hematology/Oncology

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More than half of the patients with high-risk neuroblastoma (NB) will relapse despite intensive multimodal therapy, with an additional 10% to 20% refractory to induction chemotherapy. Management of these patients is challenging, given disease heterogeneity, resistance, and organ toxicity including poor hematological reserve. This review will discuss the current treatment options and consider novel therapies on the horizon. Cytotoxic chemotherapy regimens for relapse and refractory NB typically center on the use of the camptothecins, topotecan and irinotecan, in combination with agents such as cyclophosphamide and temozolomide, with objective responses but poor long-term survival. I-meta-iodobenzylguanidine therapy is also effective for relapsed patients with meta-iodobenzylguanidine-avid disease, with objective responses in a third of cases. Immunotherapy with anti-GD2 has recently been incorporated into upfront therapy, but its role in the relapse setting remains uncertain, especially for patients with bulky disease. Future cell-based immunotherapies and other approaches may be able to overcome this limitation. Finally, many novel molecularly targeted agents are in development, some of which show specific promise for NB. Successful incorporation of these agents will require combinations with conventional cytotoxic chemotherapies, as well as the development of predictive biomarkers, to ultimately personalize approaches to patients with "targetable" molecular abnormalities.

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Section: I-mibg Therapymentioning

confidence: 99%

Current and Future Strategies for Relapsed Neuroblastoma

Morgenstern

Baruchel

Irwin

2013

Journal of Pediatric Hematology/Oncology

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“…The development of no-carrier added high specific activity 131 I-MIBG offers one strategy for improved treatment efficacy of this form of radiotherapy [41,42]. Data from preclinical studies has indicated higher uptake by tissues and tumors of the no-carrier added 131 I-MIBG than of the lower specific activity form [41].…”

Section: Future Challenges For Effective Treatmentmentioning

confidence: 99%

Current Progress and Future Challenges in the Biochemical Diagnosis and Treatment of Pheochromocytomas and Paragangliomas

Eisenhofer¹,

Siegert²,

Kotzerke³

et al. 2008

Horm Metab Res

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Findings from five independent studies -with close to 350 patients with pheochromocytoma and more than 2 500 in whom the tumor was excluded -indicate that measurements of plasma free metanephrines provide an overall diagnostic sensitivity of 98 % and specificity of 92 %. The recommendation that initial testing for the tumor should always include measurements of either plasma or urinary fractionated metanephrines results from recognition of the high diagnostic sensitivity of measurements of plasma metanephrines. The few patients with pheochromocytoma in whom the test may not yield a positive result include those with very small tumors or microscopic disease and others with tumors that do not produce norepinephrine and epinephrine. Such patients are typically normotensive and do not exhibit symptoms of catecholamine excess. Additional measurements of methoxytyramine can be useful for detecting those tumors that produce only dopamine. Suboptimal diagnostic specificity and difficulties in distinguishing truefrom false-positive elevations of plasma metanephrines remain challenges for diagnosis. Improvements in analytical technology (e.g., liquid chromatography with tandem mass spectrometry) and new strategies for follow-up testing provide possible solutions to these problems. The single most important remaining clinical care challenge is the development of effective cures for patients with malignant disease. Current treatments, none of which are truly satisfactory, include chemotherapy and radiopharmaceutical therapy with 131 I-labelled miodobenzylguanidine or radioactive somatostatin analogues. Improvements in treatment may in the future come from several fronts, but proof of efficacy ideally will require well-coordinated multicenter prospective trials in larger numbers of patients than in previous studies.

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“…For in vivo experiments, no-carrier-added 131 I-MIBG was prepared using a solid-phase system for which the precursor of 131 I-MIBG was attached to an insoluble polymer via the tin-aryl bond (23,24). For in vitro experiments, no-carrier-added 131 I-MIBG was prepared using a liquid phase system, with the trimethylsily precursor (ABX) (25).…”

Section: No-carrier-added Synthesis Of 131 I-mibg Via Polymer-supportmentioning

confidence: 99%

“…For in vitro experiments, no-carrier-added 131 I-MIBG was prepared using a liquid phase system, with the trimethylsily precursor (ABX) (25). The reaction conditions, high-performance liquid chromatography purification procedure, and radiochemical yield were as described previously (24).…”

Section: No-carrier-added Synthesis Of 131 I-mibg Via Polymer-supportmentioning

confidence: 99%

Inhibition of Poly(ADP-Ribose) Polymerase Enhances the Toxicity of ¹³¹I-Metaiodobenzylguanidine/Topotecan Combination Therapy to Cells and Xenografts That Express the Noradrenaline Transporter

McCluskey

Mairs²,

Tesson³

et al. 2012

J Nucl Med

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Targeted radiotherapy using 131 I-metaiodobenzylguanidine ( 131 I-MIBG) has produced remissions in some neuroblastoma patients. We previously reported that combining 131 I-MIBG with the topoisomerase I inhibitor topotecan induced long-term DNA damage and supraadditive toxicity to noradrenaline transporter (NAT)-expressing cells and xenografts. This combination treatment is undergoing clinical evaluation. This present study investigated the potential of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP-1) inhibition, in vitro and in vivo, to further enhance 131 I-MIBG/topotecan efficacy. Methods: Combinations of topotecan and the PARP-1 inhibitor PJ34 were assessed for synergism in vitro by combination-index analysis in SK-N-BE(2c) (neuroblastoma) and UVW/NAT (NAT-transfected glioma) cells. Three treatment schedules were evaluated: topotecan administered 24 h before, 24 h after, or simultaneously with PJ34. Combinations of PJ34 and 131 I-MIBG and of PJ34 and 131 I-MIBG/topotecan were also assessed using similar scheduling. In vivo efficacy was measured by growth delay of tumor xenografts. We also assessed DNA damage by gH2A.X assay, cell cycle progression by fluorescence-activated cell sorting analysis, and PARP-1 activity in treated cells. Results: In vitro, only simultaneous administration of topotecan and PJ34 or PJ34 and 131 I-MIBG induced supraadditive toxicity in both cell lines. All scheduled combinations of PJ34 and 131 I-MIBG/topotecan induced supraadditive toxicity and increased DNA damage in SK-N-BE(2c) cells, but only simultaneous administration induced enhanced efficacy in UVW/NAT cells. The PJ34 and 131 I-MIBG/ topotecan combination treatment induced G 2 arrest in all cell lines, regardless of the schedule of delivery. In vivo, simultaneous administration of PJ34 and 131 I-MIBG/topotecan significantly delayed the growth of SK-N-BE(2c) and UVW/NAT xenografts, compared with 131 I-MIBG/topotecan therapy. Conclusion: The antitumor efficacy of topotecan, 131 I-MIBG, and 131 I-MIBG/ topotecan combination treatment was increased by PARP-1 inhibition in vitro and in vivo.

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Preclinical Evaluation of no-Carrier-Added [131I]Meta-Iodobenzyl Guanidine, for the Treatment of Tumours Transfected with the Noradrenaline Transporter Gene

Cited by 16 publications

References 1 publication

Current and Future Strategies for Relapsed Neuroblastoma

Current and Future Strategies for Relapsed Neuroblastoma

Current Progress and Future Challenges in the Biochemical Diagnosis and Treatment of Pheochromocytomas and Paragangliomas

Inhibition of Poly(ADP-Ribose) Polymerase Enhances the Toxicity of ¹³¹I-Metaiodobenzylguanidine/Topotecan Combination Therapy to Cells and Xenografts That Express the Noradrenaline Transporter

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Preclinical Evaluation of no-Carrier-Added [131I]Meta-Iodobenzyl Guanidine, for the Treatment of Tumours Transfected with the Noradrenaline Transporter Gene

Cited by 16 publications

References 1 publication

Current and Future Strategies for Relapsed Neuroblastoma

Current and Future Strategies for Relapsed Neuroblastoma

Current Progress and Future Challenges in the Biochemical Diagnosis and Treatment of Pheochromocytomas and Paragangliomas

Inhibition of Poly(ADP-Ribose) Polymerase Enhances the Toxicity of 131I-Metaiodobenzylguanidine/Topotecan Combination Therapy to Cells and Xenografts That Express the Noradrenaline Transporter

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Inhibition of Poly(ADP-Ribose) Polymerase Enhances the Toxicity of ¹³¹I-Metaiodobenzylguanidine/Topotecan Combination Therapy to Cells and Xenografts That Express the Noradrenaline Transporter