Feasibility study of applying ICRP biokinetic models for pharmacokinetic modelling of alpha-emitter thorium-227 used in targeted radionuclide therapy

Li, W.B.; Zhernosekov, K.; Höllriegl, V.; Meckel, M.; Ziegler, S.; Konijnenberg, M.W.; Shi, Kuangyu (2018). Feasibility study of applying ICRP biokinetic models for pharmacokinetic modelling of alpha-emitter thorium-227 used in targeted radionuclide therapy. European journal of nuclear medicine and molecular imaging, 45(S1), S125-S125. Springer-Verlag

Aim: Targeted radionuclide therapy with Th-227 conjugated with novel antibodies, e.g. CD33 and CD70 has been pre-clinically used for treatment of myeloid leukaemia and renal cell carcinoma, respectively. Furthermore, PSMA-targeted Th-227 conjugate PSMA- TTC was recently developed for preclinical pharmacological study of treatment of prostate cancer. The imaging of alpha-emitter labelled radiopharmaceuticals in clinical practice is challenging. Therefore theoretical modelling of bio-distributions of Th-227 and its immediate decay product Ra-223 and other progeny is highly desired. Especially radiolabelled metabolites or unconjugated daughters may lead to toxicity but also might be beneficial in the case of unconjugated Ra-223 targeting metastatic bone lesions. Materials and methods: The current ICRP systemic biokinetic model structure and transfer parameters of thorium were taken as the prior model and parameters for pharmacokinetic modelling. Because the immediate decay product Ra-223 is another high LET alpha-emitter which can potentially be toxic to healthy tissues, the biokinetic model of radium was coupled to that for Th-227. By doing so, the bio-distributions of Th-227 and Ra-223 in human body can be simultaneously monitored. Furthermore, other decay products were as well taken into account and connected to Ra-223 as independent biokinetic models. Results: Model predictions show that 67% of Th-227 leaves blood with a clearance half-life of 6 h and deposits on the bone surface, 6% of Th-227 deposits in the liver and 4.5% of Th-227 deposits in the kidneys. The progeny Ra-223 deposits a similar activity in the alimentary tract and in the liver as the parent Th-227. The retentions of Ra-223 as progeny in kidneys and testes are about 8% of that of parent Th-227. Conclusion: The modelled pharmacokinetic bio-distributions of Th-227 and its decay products can be used as start distributions for local kinetic analysis, such as bone surface, volume, marrow and blood. The bio-distributions of decay products can be further used for patient dosimetry assessments.

Item Type:

Conference or Workshop Item (Abstract)

Division/Institute:

04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine

UniBE Contributor:

Shi, Kuangyu

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1619-7070

Publisher:

Springer-Verlag

Language:

English

Submitter:

Sabine Lanz

Date Deposited:

07 Jun 2019 09:54

Last Modified:

07 Jun 2019 09:54

Additional Information:

OP-386

URI:

https://boris.unibe.ch/id/eprint/126209

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