Safety and efficacy of targeted alpha therapy with 213Bi-DOTA-substance P in recurrent glioblastoma

Królicki, Leszek; Bruchertseifer, Frank; Kunikowska, Jolanta; Koziara, Henryk; Królicki, Bartosz; Jakuciński, Maciej; Pawlak, Dariusz; Apostolidis, Christos; Mirzadeh, Saed; Rola, Rafał; Merlo, Adrian; Morgenstern, Alfred

doi:10.1007/s00259-018-4225-7

Cited by 87 publications

(96 citation statements)

References 36 publications

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“…In this sense, recent therapeutic strategies in which the SP/NK-1R is involved have shown excellent results. Thus, in a patient treated with radiotherapy and a NK-1R antagonist (aprepitant, 1,140 mg/day for 45 days), the tumor mass disappeared after six months and no serious side-effects were observed [52] and in patients with cancer the efficacy (promoting apoptosis) of targeted alpha therapy with 213 Bi-DOTA-SP (radionuclide tumor therapy) against tumor cells has been reported [53][54][55][56][57]. Another important finding is that SP, in cancer cells, augmented the expression of the NK-1R…”

Section: The Sp/nk-1r System and Cancer: Cell Signaling Pathways Ovementioning

confidence: 99%

The Neurokinin-1 Receptor Antagonist Aprepitant, a New Drug for the Treatment of Hematological Malignancies: Focus on Acute Myeloid Leukemia

Muñoz

Coveñas

2020

Preprint

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Acute myeloid leukemia (AML) is an incurable hematological malignancy. To treat the disease successfully, new therapeutic strategies are urgently needed. One of these strategies can be the use of neurokinin-1 receptor (NK-1R) antagonists (e.g., aprepitant), because the substance P (SP)/NK-1R system is involved in cancer progression, including AML. AML patients show an up-regulation of the NK-1R mRNA expression; human AML cell lines show immunoreactivity for both SP and the NK-1R (it is overexpressed: the truncated isoform is more expressed than the full-length form) and, via this receptor, SP and NK-1R antagonists (aprepitant, in a concentration-dependent manner) respectively exert a proliferative action or an antileukemic effect (apoptotic mechanisms are triggered by promoting oxidative stress via mitochondrial Ca ++ overload). Aprepitant inhibits the formation of AML cell colonies and, in combination with chemotherapeutic drugs, is more effective in inducing cytotoxic effects and AML cell growth blockade. NK-1R antagonists also exert an antinociceptive effect in myeloid leukemia-induced bone pain. The antitumor effect of aprepitant is diminished when the NF-κB pathway is overactivated and the damage induced by aprepitant in cancer cells is higher than that exerted in non-cancer cells.Thus, the SP/NK-1R system is involved in AML and aprepitant is a promising antitumor strategy against this hematological malignancy. In this review, the involvement of this system in solid and non-solid tumors (in particular in AML) is up-dated and the use of aprepitant as an anti-leukemic strategy for the treatment of AML is also mentioned (a dose of aprepitant (> 20 mg/kg/day) for a period of time according to the response to treatment is suggested).

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Section: The Sp/nk-1r System and Cancer: Cell Signaling Pathways Ovementioning

confidence: 99%

The Neurokinin-1 Receptor Antagonist Aprepitant, a New Drug for the Treatment of Hematological Malignancies: Focus on Acute Myeloid Leukemia

Muñoz

Coveñas

2020

Preprint

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“…For theranostic purposes, neurokinin type-1 receptor can be targeted by 8 , Met(O 2 ) 11 ]-substance P ([ 213 Bi]Bi-DOTA-SP), an α-particle emitting radionuclide. Today's literature comprises two studies investigating the therapeutic use of [ 213 Bi]Bi-DOTA-SP in CNS tumors: one study including nine patients and a second study including 20 patients with recurrent GBM [112,113]. In both studies, patients received localized PRRT by an intracavitary injection of [ 213 Bi]Bi-DOTA-SP with the co-injection of [ 68 Ga]Ga-DOTA-SP for imaging purposes to assess pharmacokinetics and biodistribution.…”

Section: Pet Tracers For Guiding Targeted Radionuclide Therapy (Iementioning

confidence: 99%

“…In both studies, patients received localized PRRT by an intracavitary injection of [ 213 Bi]Bi-DOTA-SP with the co-injection of [ 68 Ga]Ga-DOTA-SP for imaging purposes to assess pharmacokinetics and biodistribution. These analyses showed tracer uptake to be concentrated in the target lesions, with low systemic uptake (i.e., less than 5% of the total activity) in the kidneys and urine [112,113].…”

Section: Pet Tracers For Guiding Targeted Radionuclide Therapy (Iementioning

confidence: 99%

The Added Value of Diagnostic and Theranostic PET Imaging for the Treatment of CNS Tumors

Pruis

Dongen

Zanten

2020

IJMS

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This review highlights the added value of PET imaging in Central Nervous System (CNS) tumors, which is a tool that has rapidly evolved from a merely diagnostic setting to multimodal molecular diagnostics and the guidance of targeted therapy. PET is the method of choice for studying target expression and target binding behind the assumedly intact blood–brain barrier. Today, a variety of diagnostic PET tracers can be used for the primary staging of CNS tumors and to determine the effect of therapy. Additionally, theranostic PET tracers are increasingly used in the context of pharmaceutical and radiopharmaceutical drug development and application. In this approach, a single targeted drug is used for PET diagnosis, upon the coupling of a PET radionuclide, as well as for targeted (nuclide) therapy. Theranostic PET tracers have the potential to serve as a non-invasive whole body navigator in the selection of the most effective drug candidates and their most optimal dose and administration route, together with the potential to serve as a predictive biomarker in the selection of patients who are most likely to benefit from treatment. PET imaging supports the transition from trial and error medicine to predictive, preventive, and personalized medicine, hopefully leading to improved quality of life for patients and more cost-effective care.

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“…The treatment was found to be safe without severe adverse effects. A subgroup analysis in patients with recurrent glioblastoma showed prolonged survival in patients treated with targeted alpha therapy compared to historical controls treated with standard therapy only, including tumour resection, radiotherapy, and temozolomide [7]. Widespread glioma cell infiltration into normal adjacent brain areas is the main cause for failure of glioma treatment.…”

Section: Ac-and 213 Bi-dotatoc For Therapy Of Neuroendocrine Tumorsmentioning

confidence: 99%

“…In recent years, several promising compounds labelled with 225 Actinium or 213 Bismuth have been developed for targeted alpha therapy of bladder cancer [1], neuroendocrine [2,3] and brain tumours [4][5][6][7], as well as prostate cancer [8][9][10][11][12][13]. Although the remarkable therapeutic results obtained with 225 Ac-PSMA-617 for therapy of advanced prostate cancer have mainly stimulated the recent rise in global interest in targeted alpha therapy, other compounds such as 213 Bi-/ 225 Ac-Substance P for therapy of brain tumours, 213 Bi-/ 225 Ac-DO-TATOC for therapy of neuroendocrine tumours, or 213 Bilabelled anti-EGFR antibodies for locoregional treatment of bladder cancer also have shown great promise and deserve further study.…”

Section: Introductionmentioning

confidence: 99%

Development of Targeted Alpha Therapy from Bench to Bedside

Morgenstern

Bruchertseifer

2019

Journal of Medical Imaging and Radiation Sciences

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Safety and efficacy of targeted alpha therapy with 213Bi-DOTA-substance P in recurrent glioblastoma

Cited by 87 publications

References 36 publications

The Neurokinin-1 Receptor Antagonist Aprepitant, a New Drug for the Treatment of Hematological Malignancies: Focus on Acute Myeloid Leukemia

The Neurokinin-1 Receptor Antagonist Aprepitant, a New Drug for the Treatment of Hematological Malignancies: Focus on Acute Myeloid Leukemia

The Added Value of Diagnostic and Theranostic PET Imaging for the Treatment of CNS Tumors

Development of Targeted Alpha Therapy from Bench to Bedside

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