Feasibility of Dosimetry-Based High-Dose <sup>131</sup>I-Meta-Iodobenzylguanidine with Topotecan as a Radiosensitizer in Children with Metastatic Neuroblastoma

Gaze, Mark; Chang, Yen-Ching; Flux, Glenn; Mairs, Robert J.; Saran, Frank; Meller, S

doi:10.1089/cbr.2005.20.195

Cited by 137 publications

(122 citation statements)

References 12 publications

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“…The original motivation was a clinical situation when the activity to administer, calculated according to the schedule by Gaze et al (2005), exceeded the maximum authorised activity limit of 14.8 GBq. For patients exceeding 33 kg, the prescription 444 MBq/kg can thus not be followed at the Gurutzeta-Cruces University Hospital.…”

Section: Discussionmentioning

confidence: 99%

Biologically effective dose in fractionated molecular radiotherapy—application to treatment of neuroblastoma with¹³¹I-mIBG

et al. 2016

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In this work, the biologically effective dose (BED) is investigated for fractionated molecular radiotherapy (MRT). A formula for the Lea–Catcheside G-factor is derived which takes the possibility of combinations of sub-lethal damage due to radiation from different administrations of activity into account. In contrast to the previous formula, the new G-factor has an explicit dependence on the time interval between administrations. The BED of tumour and liver is analysed in MRT of neuroblastoma with 131I-mIBG, following a common two-administration protocol with a mass-based activity prescription. A BED analysis is also made for modified schedules, when due to local regulations there is a maximum permitted activity for each administration. Modifications include both the simplistic approach of delivering this maximum permitted activity in each of the two administrations, and also the introduction of additional administrations while maintaining the protocol-prescribed total activity. For the cases studied with additional (i.e. more than two) administrations, BED of tumour and liver decreases at most 12% and 29%, respectively. The decrease in BED of the tumour is however modest compared to the two-administration schedule using the maximum permitted activity, where the decrease compared to the original schedule is 47%.

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Section: Discussionmentioning

confidence: 99%

Biologically effective dose in fractionated molecular radiotherapy—application to treatment of neuroblastoma with¹³¹I-mIBG

et al. 2016

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“…• Two studies investigated MIBG combined with a camptothecin, with tolerable toxicity and measurable response [36,37].…”

Section: Targeting Human Norepinephrine Transporter (Hnet) With 131 Imentioning

confidence: 99%

Target Therapy in Neuroblastoma

Hassan¹,

Badr²,

Safy³

et al. 2017

Neuroblastoma - Current State and Recent Updates

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Neuroblastoma is an embryonal malignancy that originates in the sympathetic nervous system. It is the most common solid tumor in infants and the most frequent extracranial solid tumor in children. Neuroblastoma accounts for 10% of childhood malignancies with 75% occurring in children <4 years. Stage, age, clinical and tumor genomic features are the principal criteria for determining treatment policy. Treatment modalities traditionally employed in the management of neuroblastoma are surgery, chemotherapy, and radiotherapy. Intensive multimodal treatment in patients with neuroblastoma has resulted in improved survival rates. However, there is a considerable percentage of patients with refractory and relapsed disease. Targeted therapy for neuroblastoma involves treatment aimed at molecular targets that have a unique expression in this childhood cancer. A large number of molecular targets have been identified for the treatment of high-risk and relapsed neuroblastoma. Treatment in this way aims at providing a more selective way to treat the disease and decreasing toxicities associated with the conventional treatment regimen.

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“…On the basis of our findings, clinical investigations of MATIN (MIBG and Topotecan in Neuroblastoma) have commenced (16). To date, more than 70 patients in 5 institutions across Europe have been enrolled in MATIN.…”

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confidence: 91%

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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Feasibility of Dosimetry-Based High-Dose ¹³¹I-Meta-Iodobenzylguanidine with Topotecan as a Radiosensitizer in Children with Metastatic Neuroblastoma

Cited by 137 publications

References 12 publications

Biologically effective dose in fractionated molecular radiotherapy—application to treatment of neuroblastoma with¹³¹I-mIBG

Biologically effective dose in fractionated molecular radiotherapy—application to treatment of neuroblastoma with¹³¹I-mIBG

Target Therapy in Neuroblastoma

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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Feasibility of Dosimetry-Based High-Dose 131I-Meta-Iodobenzylguanidine with Topotecan as a Radiosensitizer in Children with Metastatic Neuroblastoma

Cited by 137 publications

References 12 publications

Biologically effective dose in fractionated molecular radiotherapy—application to treatment of neuroblastoma with131I-mIBG

Biologically effective dose in fractionated molecular radiotherapy—application to treatment of neuroblastoma with131I-mIBG

Target Therapy in Neuroblastoma

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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Feasibility of Dosimetry-Based High-Dose ¹³¹I-Meta-Iodobenzylguanidine with Topotecan as a Radiosensitizer in Children with Metastatic Neuroblastoma

Biologically effective dose in fractionated molecular radiotherapy—application to treatment of neuroblastoma with¹³¹I-mIBG

Biologically effective dose in fractionated molecular radiotherapy—application to treatment of neuroblastoma with¹³¹I-mIBG

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