In Vivo Radionuclide Generators for Diagnostics and Therapy

Edem, Patricia E.; Fonslet, Jesper; Kjær, Andreas; Herth, Matthias M.; Severin, Gregory

doi:10.1155/2016/6148357

Cited by 35 publications

(23 citation statements)

References 47 publications

(59 reference statements)

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“…Different approaches have been explored to inhibit the accumulation of both parent and daughter radionuclides in critical organs or acceleration of their clearance: co-injection of lysine with 213 Bi-labelled conjugate can reduce kidney uptake of 213 Bi [ 64 ], bismuth citrate pre-treatment blocks renal retention of 213 Bi [ 65 ], and oral administration of BaSO 4 known as a coprecipitating agent of radium reduces the 223 Ra accumulation in the large intestine [ 66 ]. In some cases only locoregional therapy (not intravenous injection) is suited because of the large size or high hydrophilicity of the delivery agent, e.g., encapsulated liposomes or multi-layered nanoconstructs [ 67 ]. Imaging methods with the potential for in vivo evaluation of the pharmacokinetics of the radionuclides, such as single-photon emission computed tomography (SPECT)/PET/CT imaging are of great importance for assessing the outcome of the therapy.…”

Section: General Radiopharmaceutical Issuesmentioning

confidence: 99%

Progress in Targeted Alpha-Particle Therapy. What We Learned about Recoils Release from In Vivo Generators

2018

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This review summarizes recent progress and developments as well as the most important pitfalls in targeted alpha-particle therapy, covering single alpha-particle emitters as well as in vivo alpha-particle generators. It discusses the production of radionuclides like 211At, 223Ra, 225Ac/213Bi, labelling and delivery employing various targeting vectors (small molecules, chelators for alpha-emitting nuclides and their biomolecular targets as well as nanocarriers), general radiopharmaceutical issues, preclinical studies, and clinical trials including the possibilities of therapy prognosis and follow-up imaging. Special attention is given to the nuclear recoil effect and its impacts on the possible use of alpha emitters for cancer treatment, proper dose estimation, and labelling chemistry. The most recent and important achievements in the development of alpha emitters carrying vectors for preclinical and clinical use are highlighted along with an outlook for future developments.

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Section: General Radiopharmaceutical Issuesmentioning

confidence: 99%

Progress in Targeted Alpha-Particle Therapy. What We Learned about Recoils Release from In Vivo Generators

2018

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“…Consequently, only 2-3 α-particles are needed to kill a single cell, compared to 100-1000 low LET β-particles [14]. 212 Pb has two alternative decay pathways through α-emitting daughters, 212 Bi or 212 Po, and can therefore be used as an in vivo generator of α-particles [15].…”

Section: Introductionmentioning

confidence: 99%

Targeted alpha therapy for chronic lymphocytic leukaemia and non-Hodgkin’s lymphoma with the anti-CD37 radioimmunoconjugate 212Pb-NNV003

et al. 2020

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Relapse of chronic lymphocytic leukaemia and non-Hodgkin's lymphoma after standard of care treatment is common and new therapies are needed. The targeted alpha therapy with 212 Pb-NNV003 presented in this study combines cytotoxic α-particles from 212 Pb, with the anti-CD37 antibody NNV003, targeting B-cell malignancies. The goal of this study was to explore 212 Pb-NNV003 for treatment of CD37 positive chronic lymphocytic leukaemia and non-Hodgkin's lymphoma in preclinical mouse models.An anti-proliferative effect of 212 Pb-NNV003 was observed in both chronic lymphocytic leukaemia (MEC-2) and Burkitt's lymphoma (Daudi) cells in vitro. In biodistribution experiments, accumulation of 212 Pb-NNV003 was 23%ID/g and 16%ID/g in Daudi and MEC-2 tumours 24 h post injection. In two intravenous animal models 90% of the mice treated with a single injection of 212 Pb-NNV003 were alive 28 weeks post cell injection. Median survival times of control groups were 5-9 weeks. There was no significant difference between different specific activities of 212 Pb-NNV003 with regards to therapeutic effect or toxicity. For therapeutically effective activities, a transient haematological toxicity was observed. This study shows that 212 Pb-NNV003 is effective and safe in preclinical models of CD37 positive chronic lymphocytic leukaemia and non-Hodgkin's lymphoma, warranting future clinical testing.

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“…This rich choice of carrier, together with the availability of a range of isotopes with unique physicochemical properties, allows vector-radioisotope pairings to be tailored precisely to specific clinical scenarios. With the availability of generators for in-house production of therapeutic radiopharmaceuticals, 6 the use of radionuclide therapy is increasing. In the UK there was a 38% increase in the number of treatments during the 5-year period 2007 to 2012, and this increase is likely to continue with the adoption into practise of 90 Y-labelled microspheres for the treatment of hepatic tumours, 223 RaCl2 for metastatic castrate-resistant prostate cancer (mCRPC) and 177 Lu-Dotatate (DOTA-TATE or DOTA-octreotate) for neuroendocrine tumours.…”

Section: Introductionmentioning

confidence: 99%

Targeted radionuclide therapy in combined-modality regimens

Gill

Falzone

et al. 2017

The Lancet Oncology

135

126

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Targeted radionuclide therapy (TRT) is a branch of cancer medicine concerned with the use of radioisotopes, radiolabelled molecules, nanoparticles, or microparticles that either naturally accumulate in or are designed to target tumours. TRT combines the specificity of molecular and sometimes physical targeting with the potent cytotoxicity of ionising radiation. Targeting vectors for TRT include antibodies, antibody fragments, proteins, peptides, and small molecules. The diversity of available carrier molecules, together with the large panel of suitable radioisotopes with unique physicochemical properties, allows vector-radionuclide pairings to be matched to the molecular, pathological, and physical characteristics of a tumour. Some pairings are designed for dual therapeutic and diagnostic applications. Use of TRT is increasing with the adoption into practice of radium-223 dichloride for the treatment of bone metastases and with the ongoing clinical development of, among others, Lu-dodecanetetraacetic acid tyrosine-3-octreotate (DOTATATE) for the treatment of neuroendocrine tumours andY-microspheres for the treatment of hepatic tumours. The increasing use of TRT raises the question of how best to integrate TRT into multimodality protocols. Achievements in this area and the future prospects of TRT are evaluated in this Review.

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In Vivo Radionuclide Generators for Diagnostics and Therapy

Cited by 35 publications

References 47 publications

Progress in Targeted Alpha-Particle Therapy. What We Learned about Recoils Release from In Vivo Generators

Progress in Targeted Alpha-Particle Therapy. What We Learned about Recoils Release from In Vivo Generators

Targeted alpha therapy for chronic lymphocytic leukaemia and non-Hodgkin’s lymphoma with the anti-CD37 radioimmunoconjugate 212Pb-NNV003

Targeted radionuclide therapy in combined-modality regimens

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