Systemic Endoradiotherapy with Carrier-Added 4-[131I]Iodo-L-Phenylalanine: Clinical Proof-of-Principle in Refractory Glioma

Baüm, Richard; Kluge, Andreas; Gildehaus, Franz Josef; Bronzel, Marcus; Schmidt, Karl F.; Schuchardt, Christiane; Senftleben, Stephan; Samnick, Samuel

doi:10.1007/s13139-011-0116-6

Cited by 13 publications

(7 citation statements)

References 21 publications

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“…Therefore, we thought that para-211 At-PA uptake could be more specific to system L amino acid transporters. In addition, para-iodo-Lphenylalanine labelled with 123 I/ 131 I has been reported to show high uptake in glioma patients [7][8][9], suggesting the best coupling to be para-iodo/astato-L-phenylalanine.…”

Section: Discussionmentioning

confidence: 99%

“…The derivative labelled with the gamma emitting isotope, para-123 I-iodo-L-phenylalanine ( 123 I-IPA), has been used with some success as a diagnostic imaging agent in glioblastoma patients [7]. The corresponding 131 I derivative ( 131 I-IPA) has been studied as a therapeutic agent, and is currently being advanced as a combination therapy with external beam radiation in a PhaseI/II clinical trial [8,9]. These PA-based compounds exhibit characteristics of high tumor to normal brain ratio that would be ideal for a targeted alpha therapeutic strategy.…”

Section: Research Papermentioning

confidence: 99%

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Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

et al. 2020

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Phenylalanine derivatives, which target tumors especially through L-type amino acid transporter-1 (LAT1), have elicited considerable attention. In this study, we evaluated the treatment effect of phenylalanine labeled with the alpha emitter astatine ( 211 At-PA) in tumor bearing mice. The C6 glioma, U-87MG, and GL261 cell lines were subjected to a cellular 211 At-PA uptake analysis that included an evaluation of the uptake inhibition by the system L amino acid transporter inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). BCH significantly inhibited para-211 At-PA uptake in C6 glioma (12.2 ± 0.8%), U-87MG (27.6 ± 1.1%), and GL261 (12.6 ± 2.0%) cells compared to baseline, suggesting an uptake contribution by system L amino acid transporters. Subsequently, xenograft and allograft models were prepared by subcutaneously injecting C6 glioma (n = 12) or GL-261 cells (n = 12), respectively. C6 glioma mice received three 211 At-PA doses (0.1, 0.5, or 1 MBq, n = 3/dose), while GL261 mice received one high dose (1 MBq, n = 7). 211 At-PA exhibited a tumor growth suppression effect in C6 glioma models in a dose-dependent manner as well as in GL-261 models. This phenylalanine derivative labeled with astatine may be applicable as an alpha therapy that specifically targets system L amino acid transporters.

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Section: Discussionmentioning

confidence: 99%

Section: Research Papermentioning

confidence: 99%

Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

et al. 2020

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“…In a human trial of systemic endo radio-therapy with [ 131 I]iodo-IPA (up to 6.6 GBq), patients did not present with acute or late radiotoxicity, neurotoxicity, and haematological or renal adverse events were not observed. This first-in-human investigation was performed in two patients with progressive gliomas, which were initially diagnosed as low-grade astrocytoma (WHO II) and oligodendroglioma (WHO II), respectively [240].…”

Section: Iodine-131mentioning

confidence: 99%

A perspective on the radiopharmaceutical requirements for imaging and therapy of glioblastoma

Bolcaen¹,

Kleynhans²,

Nair³

et al. 2021

Theranostics

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Despite numerous clinical trials and pre-clinical developments, the treatment of glioblastoma (GB) remains a challenge. The current survival rate of GB averages one year, even with an optimal standard of care. However, the future promises efficient patient-tailored treatments, including targeted radionuclide therapy (TRT). Advances in radiopharmaceutical development have unlocked the possibility to assess disease at the molecular level allowing individual diagnosis. This leads to the possibility of choosing a tailored, targeted approach for therapeutic modalities. Therapeutic modalities based on radiopharmaceuticals are an exciting development with great potential to promote a personalised approach to medicine. However, an effective targeted radionuclide therapy (TRT) for the treatment of GB entails caveats and requisites. This review provides an overview of existing nuclear imaging and TRT strategies for GB. A critical discussion of the optimal characteristics for new GB targeting therapeutic radiopharmaceuticals and clinical indications are provided. Considerations for target selection are discussed, i.e. specific presence of the target, expression level and pharmacological access to the target, with particular attention to blood-brain barrier crossing. An overview of the most promising radionuclides is given along with a validation of the relevant radiopharmaceuticals and theranostic agents (based on small molecules, peptides and monoclonal antibodies). Moreover, toxicity issues and safety pharmacology aspects will be presented, both in general and for the brain in particular.

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“…1 ) (Kratochwil et al 2014 ; Morita et al 2013 ; Hellwig et al 2008 ; Kersemans et al 2006 ). In addition, radiotherapy using β − -emitting radionuclide 131 I, para -[ 131 I]-iodo-L-phenylalanine ([ 131 I]-IPA) was also being investigated as a therapeutic agent and had shown efficacy in cancer treatment in clinical trials (Baum et al 2011 ). Recent reports have often suggested that radiolabeled compounds containing α-ray emitting radionuclides showed better therapeutic effects than those using β − -emitting radionuclides (McDevitt et al 2018 ; Morgenstern et al 2020 ; Sgouros et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Neopentyl glycol-based radiohalogen-labeled amino acid derivatives for cancer radiotheranostics

Kaizuka,

Suzuki,

Watabe

et al. 2024

EJNMMI radiopharm. chem.

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Background L-type amino acid transporter 1 (LAT1) is overexpressed in various cancers; therefore, radiohalogen-labeled amino acid derivatives targeting LAT1 have emerged as promising candidates for cancer radiotheranostics. However, 211At-labeled amino acid derivatives exhibit instability against deastatination in vivo, making it challenging to use 211At for radiotherapy. In this study, radiohalogen-labeled amino acid derivatives with high dehalogenation stability were developed. Results We designed and synthesized new radiohalogen-labeled amino acid derivatives ([211At]At-NpGT, [125I]I-NpGT, and [18F]F-NpGT) in which L-tyrosine was introduced into the neopentyl glycol (NpG) structure. The radiolabeled amino acid derivatives were recognized as substrates of LAT1 in the in vitro studies using C6 glioma cells. In a biodistribution study using C6 glioma-bearing mice, these agents exhibited high stability against in vivo dehalogenation and similar biodistributions. The similarity of [211At]At-NpGT and [18F]F-NpGT indicated that these pairs of radiolabeled compounds would be helpful in radiotheranostics. Moreover, [211At]At-NpGT exhibited a dose-dependent inhibitory effect on the growth of C6 glioma-bearing mice. Conclusions [211At]At-NpGT exhibited a dose-dependent inhibitory effect on the tumor growth of glioma-bearing mice, and its biodistribution was similar to that of other radiohalogen-labeled amino acid derivatives. These findings suggest that radiotheranostics using [18F]F-NpGT and [123/131I]I-NpGT for diagnostic applications and [211At]At-NpGT and [131I]I-NpGT for therapeutic applications are promising.

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Systemic Endoradiotherapy with Carrier-Added 4-[131I]Iodo-L-Phenylalanine: Clinical Proof-of-Principle in Refractory Glioma

Abstract: Systemic endoradiotherapy using up to 6.6 GBq of c.a.(131)I-IPA is not associated with clinically detectable toxicity. Measurable anti-tumour effects in gliomas were observed. (131)I-IPA warrants further evaluation as glioma therapy.

Cited by 13 publications

References 21 publications

Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

A perspective on the radiopharmaceutical requirements for imaging and therapy of glioblastoma

Neopentyl glycol-based radiohalogen-labeled amino acid derivatives for cancer radiotheranostics

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