The effect of the α-emitting radionuclide lead-212 on human ovarian carcinoma: A potential new form of therapy

Rotmensch, Jacob; Atcher, Robert W.; Schlenker, R.A.; Hines, John J.; Grdina, David J.; Block, Barry S.; Press, Michael F.; Herbst, Arthur L.; Weichselbaum, Ralph R.

doi:10.1016/s0090-8258(89)80040-x

Cited by 20 publications

(15 citation statements)

References 3 publications

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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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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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“…IP therapy with α-emitters has previously been examined in murine models with two carrier types: nano- to microsized particles [9] , [10] , [11] , [12] and monoclonal antibodies [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] . With particles as carriers for radionuclides, it is possible to choose a size that facilitates a high retention of the particles in the peritoneal cavity [22] , [23] and thus contribute to the therapeutic radiation being delivered in the target location.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Effect of α-Emitting 224Ra-Labeled Calcium Carbonate Microparticles in Mice with Intraperitoneal Ovarian Cancer

Westrøm

Bønsdorff

Bruland

et al. 2018

Translational Oncology

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BACKGROUND: Ovarian cancer patients with chemotherapy-resistant residual microscopic disease in the peritoneal cavity have a considerable need for new treatment options. Alpha-emitting radionuclides injected intraperitoneally may be an attractive therapeutic option in this situation as they are highly cytotoxic, while their short range in tissues can spare surrounding radiosensitive organs in the abdomen. Herein we evaluate the therapeutic efficacy of a novel α-emitting compound specifically designed for intracavitary radiation therapy. METHODS: The α-emitter 224Ra was absorbed on calcium carbonate microparticles. Immunodeficient, athymic nude mice with human ovarian cancer cells growing intraperitoneally were treated with different activity levels of 224Ra-microparticles. Tumor growth, survival, and tolerance of the treatment were assessed. Two tumor models based on the cell lines, ES-2 and SKOV3-luc, with different growth patterns were studied. RESULTS: In both models, intraperitoneal treatment with 224Ra-microparticles gave significant antitumor effect with either considerably reduced tumor volume or a survival benefit. An advantageous discovery was that only a few kilobecquerels per mouse were needed to yield therapeutic effects. The treatment was well tolerated up to a dose of 1000 kBq/kg with no signs of acute or subacute toxicity observed. CONCLUSIONS: Intraperitoneal α-therapy with 224Ra-microparticles demonstrated a significant potential for treatment of peritoneal micrometastases in ovarian carcinoma.

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“…1), is investigated using spermatogonial cell killing in mouse testis as an in vivo model. The former two radionuclides ( 212 Pb, 212 Bi), which have been proposed for therapeutic applications (14,15,17), yield a mixed radiation field of photons, β particles and α particles (18). These present results on the radiotoxicity of 212 Pb and its daughters, together with our earlier investigations in the same model with the monoenergetic α-particle emitter 210 Po (19), are used to establish a relationship between the RBE of α particles emitted by incorporated radionuclides and their energy at low, but deterministic, doses.…”

Section: Introductionmentioning

confidence: 99%

Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo at Low Doses

Howell¹,

Azure²,

Narra³

et al. 1994

Radiation Research

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The therapeutic potential of radionuclides that emit α particles, as well as their associated health hazards, have attracted considerable attention. The 224 Ra daughters 212 Pb and 212 Bi, by virtue of their radiation properties which involve emission of α and β particles in their decay to stable 208 Pb, have been proposed as candidates for radioimmunotherapy. Using mouse testes as the experimental model and testicular spermhead survival as the biological end point, the present work examines the radiotoxicity of 212 Pb and its daughters. When 212 Pb, in equilibrium with its daughters 212 Bi, 212 Po and 208 Tl, was administered directly into the testis, the dose required to achieve 37% survival (D 37 ) was 0.143 ± 0.014 Gy and the corresponding RBE of the mixed radiation field was 4.7 when compared to the D 37 for acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210 Po, was used to obtain an RBE-LET relationship for α particles emitted by tissue-incorporated radionuclides: RBE α = 4.8 − 6.1 × 10 −2 LET + 1.0 × 10 −3 LET 2 . Similarly, the dependence of RBE on α-particle energy E α was given by . These relationships, based on in vivo experimental data, may be valuable in predicting biological effects of α-particle emitters.

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The effect of the α-emitting radionuclide lead-212 on human ovarian carcinoma: A potential new form of therapy

Cited by 20 publications

References 3 publications

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

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

Therapeutic Effect of α-Emitting 224Ra-Labeled Calcium Carbonate Microparticles in Mice with Intraperitoneal Ovarian Cancer

Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo at Low Doses

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