B7-H3-targeted 212Pb radioimmunotherapy of ovarian cancer in preclinical models

Kasten, Benjamin B.; Arend, Rebecca C.; Katre, Ashwini A.; Kim, Hyung Min; Fan, Jinda; Ferrone, Soldano; Zinn, Kurt R.; Buchsbaum, Donald J.

doi:10.1016/j.nucmedbio.2017.01.003

Cited by 61 publications

(53 citation statements)

References 47 publications

(66 reference statements)

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“…When proposing use of an internal α‐emitter for cancer treatment, it is important to choose a radionuclide with physical properties apt for the application. Intraperitoneal therapy with α‐emitters has shown significant potential in murine models previously, mainly with short‐lived nuclides coupled to monoclonal antibodies . With longer lived nuclides, an unfavorable biodistribution in mice without tumors was found after IP injection of 227 Th coupled to trastuzumab .…”

Section: Discussionmentioning

confidence: 99%

Ra‐224 labeling of calcium carbonate microparticles for internal α‐therapy: Preparation, stability, and biodistribution in mice

Westrøm

Malenge

Jorstad

et al. 2018

Labelled Comp Radiopharmac

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Internal therapy with α‐emitters should be well suited for micrometastatic disease. Radium‐224 emits multiple α‐particles through its decay and has a convenient 3.6 days of half‐life. Despite its attractive properties, the use of 224Ra has been limited to bone‐seeking applications because it cannot be stably bound to a targeting molecule. Alternative delivery systems for 224Ra are therefore of considerable interest. In this study, calcium carbonate microparticles are proposed as carriers for 224Ra, designed for local therapy of disseminated cancers in cavitary regions, such as peritoneal carcinomatosis. Calcium carbonate microparticles were radiolabeled by precipitation of 224Ra on the particle surface, resulting in high labeling efficiencies for both 224Ra and daughter 212Pb and retention of more than 95% of these nuclides for up to 1 week in vitro. The biodistribution after intraperitoneal administration of the 224Ra‐labeled CaCO3 microparticles in immunodeficient mice revealed that the radioactivity mainly remained in the peritoneal cavity. In addition, the systemic distribution of 224Ra was found to be strongly dependent on the amount of administered microparticles, with a reduced skeletal uptake of 224Ra with increasing dose. The results altogether suggest that the 224Ra‐labeled CaCO3 microparticles have promising properties for use as a localized internal α‐therapy of cavitary cancers.

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Section: Discussionmentioning

confidence: 99%

Ra‐224 labeling of calcium carbonate microparticles for internal α‐therapy: Preparation, stability, and biodistribution in mice

Westrøm

Malenge

Jorstad

et al. 2018

Labelled Comp Radiopharmac

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“…The anti-tumour efficacy of 212 Pb has been demonstrated in preclinical studies; in several animal models of peritoneal cancer [16][17][18][19][20][21][22], prostate cancer, melanoma, pancreatic cancer and breast cancer [23][24][25][26]. It has also been applied in a pre-targeting setting [27,28].…”

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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“…Expression of B7-H3 in the tumor vasculature was recently exploited to improve the accuracy of a breast cancer diagnostic [5]. Preclinical radioimmunotherapy in ovarian cancer using B7-H3 antibodies radiolabeled with 212 Pb α-particles target tumor cells and vasculature and showed promising effects with low toxicity [6]. In addition, an antibody targeting B7-H3 conjugated with the DNA alkylating compound Pyrrolobenzodiazepine was shown to target both B7-H3 expressing tumor cells and vasculature [7].…”

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confidence: 99%