Metabolic Studies with Radiobismuth: I. Retention and Distribution of 206 Bi in the Normal Rat

Russ, Gerald A.; Bigler, Rodney E.; Tilbury, R.S.; Woodard, Helen Q.; Laughlin, John S.

doi:10.2307/3574096

Cited by 41 publications

(28 citation statements)

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“…Bismuth is both filtered as well as secreted. 31 It is believed that ionized bismuth (Bi 3+ ) is bound to the plasma proteins and forms a slow-clearing compartment. The kidneys can filter ~50% of 30 kD proteins, decreasing to 0.5% for 69 kD proteins.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and toxicity of 213Bi-labeled PAI2 in preclinical targeted alpha therapy for cancer

Song¹,

Rizvi²,

Qu³

et al. 2007

Cancer Biology & Therapy

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and toxicity of 213Bi-labeled PAI2 in preclinical targeted alpha therapy for cancer

Song¹,

Rizvi²,

Qu³

et al. 2007

Cancer Biology & Therapy

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“…Early studies on the metabolism of bismuth compounds suggested preferential uptake in the renal cortex (Russ et al 1975, Slikkerveer and Dewolff 1989, Szymanska et al 1977). Speidel et al (1991) showed that while bismuth isotopes were excreted through the kidney, there was non-negligible (3–5%) longer term retention.…”

Section: Introductionmentioning

confidence: 99%

Renal uptake of bismuth-213 and its contribution to kidney radiation dose following administration of actinium-225-labeled antibody

et al. 2011

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Clinical therapeutic studies using 225 Ac-labeled antibodies have begun. Of major concern is renal toxicity that may result from the three alpha-emitting progeny generated following the decay of 225 Ac. The purpose of this study was to determine the amount of 225 Ac and non-equilibrium progeny in the mouse kidney after the injection of 225 Ac-huM195 antibody and examine the dosimetric consequences. Groups of mice were sacrificed at 24, 96 and 144 h after injection with 225 Ac-huM195 antibody and kidneys excised. One kidney was used for gamma ray spectroscopic measurements by a high-purity germanium (HPGe) detector. The second kidney was used to generate frozen tissue sections which were examined by digital autoradiography (DAR). Two measurements were performed on each kidney specimen: (1) immediately post-resection and (2) after sufficient time for any non-equilibrium excess 213 Bi to decay completely. Comparison of these measurements enabled estimation of the amount of excess 213 Bi reaching the kidney (γ-ray spectroscopy) and its sub-regional distribution (DAR). The average absorbed dose to whole kidney, determined by spectroscopy, was 0.77 (SD 0.21) Gy kBq −1 , of which 0.46 (SD 0.16) Gy kBq −1 (i.e. 60%) was due to non-equilibrium excess 213 Bi. The relative contributions to renal cortex and medulla were determined by DAR. The estimated dose to the cortex from nonequilibrium excess 213 Bi (0.31 (SD 0.11) Gy kBq −1 ) represented ~46% of the total. For the medulla the dose contribution from excess 213 Bi (0.81 (SD 0.28) Gy kBq −1 ) was ~80% of the total. Based on these estimates, for human patients we project a kidney-absorbed dose of 0.28 Gy MBq −1 following administration of 225 Ac-huM195 with non-equilibrium excess 213 Bi responsible for approximately 60% of the total. Methods to reduce renal accumulation of radioactive progeny appear to be necessary for the success of 225 Ac radioimmunotherapy.

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“…The character of the tubule changes during this descent and becomes the distal tubule. The proximal tubule is the region where the free metalloids are most likely to be absorbed (41); together with the glomerulus, they are the regions which exhibit toxicity in murine studies of renal toxicity due to 225 Ac or 211 At therapy (30, 31, 33, 42), therefore the modeled version of the nephron focuses on these two sub-units.…”

Section: Methodsmentioning

confidence: 99%

A nephron-based model of the kidneys for macro-to-micro α-particle dosimetry

et al. 2012

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Targeted α-particle therapy is a promising treatment modality for cancer. Due to the short path-length of α-particles, the potential efficacy and toxicity of these agents is best evaluated by microscale dosimetry calculations instead of whole-organ, absorbed fraction-based dosimetry. Yet time-integrated activity (TIA), the necessary input for dosimetry, can still only be quantified reliably at the organ or macroscopic level. We describe a nephron-and cellular-based kidney dosimetry model for α-particle radiopharmaceutical therapy, more suited to the short range and high linear energy transfer of α-particle emitters, which takes as input kidney or cortex TIA and through a macro to micro model-based methodology assigns TIA to micro-level kidney substructures. We apply a geometrical model to provide nephron-level S-values for a range of isotopes allowing for pre-clinical and clinical applications according to the medical internal radiation dosimetry (MIRD) schema. We assume that the relationship between whole-organ TIA and TIA apportioned to microscale substructures as measured in an appropriate pre-clinical mammalian model also applies to the human. In both, the pre-clinical and the human model, microscale substructures are described as a collection of simple geometrical shapes akin to those used in the Cristy-Eckerman phantoms for normal organs. Anatomical parameters are taken from the literature for a human model, while murine parameters are measured ex vivo. The murine histological slides also provide the data for volume of occupancy of the different compartments of the nephron in the kidney: glomerulus versus proximal tubule versus distal tubule. Monte Carlo simulations are run with activity placed in the different nephron compartments for several α-particle emitters currently under investigation in radiopharmaceutical therapy. The S-values were calculated for the α-emitters and their descendants between the different nephron compartments for both the human and murine models. The renal cortex and medulla S-values were 3 Author to whom any correspondence should be addressed.

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Metabolic Studies with Radiobismuth: I. Retention and Distribution of 206 Bi in the Normal Rat

Cited by 41 publications

References 0 publications

Pharmacokinetics and toxicity of 213Bi-labeled PAI2 in preclinical targeted alpha therapy for cancer

Pharmacokinetics and toxicity of 213Bi-labeled PAI2 in preclinical targeted alpha therapy for cancer

Renal uptake of bismuth-213 and its contribution to kidney radiation dose following administration of actinium-225-labeled antibody

A nephron-based model of the kidneys for macro-to-micro α-particle dosimetry

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