Distribution of intraperitoneally injected microspheres labeled with the α-emitter astatine (211At) compared with phosphorus (32P) and yttrium (90Y) colloids in mice

Vergote, Ignace; Larsen, Roy H.; Vos, Laure De; Winderen, Mette; Ellingsen, T.; Bjørgum, Jon; Hoff, P.; Aas, Magne; Tropé, Claes G.; Nustad, Kjell

doi:10.1016/0090-8258(92)90140-e

Cited by 14 publications

(10 citation statements)

References 24 publications

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“…Studies have also been performed with short‐lived 211 At bound to polystyrene microparticles. The obtained results were promising, with favorable biodistribution and cure rates . By using microparticles as carriers for radionuclides, a longer‐lived radionuclide, like, eg, 224 Ra, might be advantageous.…”

Section: Discussionmentioning

confidence: 97%

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: 97%

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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“…Bloomer et al (1984) demonstrated that mice with malignant ascites could be cured with a single dose of 211 At-tellurium colloids but not with radiocolloids labelled with the α-emitters 32 P, 165 Dy and 90 Y. Unfortunately, the stability of this 211 Attellurium colloid was too low to contemplate clinical evaluation (Bloomer et al 1984, Vergote et al 1992a. Larsen et al (1993) recently labelled monodisperse polymer particles (MDPPs) with 211 At using N -succinimidyl 3-[ 211 At]astatobenzoate ([ 211 At]SAB), a tracer originally developed for labelling proteins (Zalutsky and Narula 1988).…”

Section: The Cytotoxicity Of [ 211 At]mabgmentioning

confidence: 99%

“…The tissue distribution of 211 At-labelled MDPPs was compared after intraperitoneal injection in mice with that of 211 At-tellurium colloid (Vergote et al 1992a). The 211 Atlabelled MDPPs spread rapidly within the peritoneal cavity and were retained mainly on the intraperitoneal surfaces, whereas with 211 At-tellurium colloid, the radioactivity diffused rapidly throughout the body, indicating a lack of stability.…”

Section: The Cytotoxicity Of [ 211 At]mabgmentioning

confidence: 99%

Targeted therapy using alpha emitters

Vaidyanathan¹,

Zalutsky²

1996

Phys. Med. Biol.

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Radionuclides such as 211At and 212Bi which decay by the emission of alpha-particles are attractive for certain applications of targeted radiotherapy. The tissue penetration of 212Bi and 211At alpha-particles is equivalent to only a few cell diameters, offering the possibility of combining cell-specific targeting with radiation of similar range. Unlike the beta-particles emitted by radionuclides such as 131I and 90Y, alpha-particles are radiation of high linear energy transfer and thus greater biological effectiveness. Several approaches have been explored for targeted radiotherapy with 212Bi- and 211At-labelled substances including colloids, monoclonal antibodies, metabolic precursors, receptor-avid ligands and other lower molecular weight molecules. An additional agent which exemplifies the promise of alpha-emitting radiopharmaceuticals is meta-[211At]astatobenzylguanidine. The toxicity of this compound under single-cell conditions, determined both by [3H]thymidine incorporation and by limiting dilution clonogenic assays, for human neuroblastoma cells is of the order of 1000 times higher than that of meta-[131I] iodobenzylguanidine. For meta-[211At] astatobenzylguanidine, the Do value was equivalent to only 6-7 211At atoms bound per cell. These results suggest that meta-[211At] astatobenzylguanidine might be valuable for the targeted radiotherapy of micrometastatic neuroblastomas.

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“…Investigators have explored the use of radiolabelled colloids, antibodies and microspheres. Colloids and antibodies have been shown to escape from the peritoneal cavity resulting in uptake in other tissues (Vergote et al 1992a, Alvarez et al 1997, Buijs et al 1988, Srivastava and Dadachova 2001. Biodistribution studies have shown that larger preparations such as microspheres exhibit better peritoneal retention (Vergote et al 1992a(Vergote et al , 1992b.…”

Section: Introductionmentioning

confidence: 99%

Dosimetric model for intraperitoneal targeted liposomal radioimmunotherapy of ovarian cancer micrometastases

Syme¹,

McQuarrie²,

Middleton³

et al. 2003

Phys. Med. Biol.

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A simple model has been developed to investigate the dosimetry of micrometastases in the peritoneal cavity during intraperitoneal targeted liposomal radioimmunotherapy. The model is applied to free-floating tumours with radii between 0.005 cm and 0.1 cm. Tumour dose is assumed to come from two sources: free liposomes in solution in the peritoneal cavity and liposomes bound to the surface of the micrometastases. It is assumed that liposomes do not penetrate beyond the surface of the tumours and that the total amount of surface antigen does not change over the course of treatment. Integrated tumour doses are expressed as a function of biological parameters that describe the rates at which liposomes bind to and unbind from the tumour surface, the rate at which liposomes escape from the peritoneal cavity and the tumour surface antigen density. Integrated doses are translated into time-dependent tumour control probabilities (TCPs). The results of the work are illustrated in the context of a therapy in which liposomes labelled with Re-188 are targeted at ovarian cancer cells that express the surface antigen CA-125. The time required to produce a TCP of 95% is used to investigate the importance of the various parameters. The relative contributions of surface-bound radioactivity and unbound radioactivity are used to assess the conditions required for a targeted approach to provide an improvement over a non-targeted approach during intraperitoneal radiation therapy. Using Re-188 as the radionuclide, the model suggests that, for microscopic tumours, the relative importance of the surface-bound radioactivity increases with tumour size. This is evidenced by the requirement for larger antigen densities on smaller tumours to affect an improvement in the time required to produce a TCP of 95%. This is because for the smallest tumours considered, the unbound radioactivity is often capable of exerting a tumouricidal effect before the targeting agent has time to accumulate significantly on the tumour surface.

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Distribution of intraperitoneally injected microspheres labeled with the α-emitter astatine (211At) compared with phosphorus (32P) and yttrium (90Y) colloids in mice

Cited by 14 publications

References 24 publications

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

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

Targeted therapy using alpha emitters

Dosimetric model for intraperitoneal targeted liposomal radioimmunotherapy of ovarian cancer micrometastases

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