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Open Access 01-12-2019 | Pharmacokinetics | Original research

A phase 0 study of the pharmacokinetics, biodistribution, and dosimetry of ¹⁸⁸Re-liposome in patients with metastatic tumors

Authors: Shyh-Jen Wang, Wen-Sheng Huang, Chi-Mu Chuang, Chih-Hsien Chang, Te-Wei Lee, Gann Ting, Ming-Huang Chen, Peter Mu-Hsin Chang, Ta-Chung Chao, Hao-Wei Teng, Yee Chao, Yuh-Min Chen, Tzu-Ping Lin, Ya-Jen Chang, Su-Jung Chen, Yuan-Ruei Huang, Keng-Li Lan

Published in: EJNMMI Research | Issue 1/2019

Abstract

Background

Liposomes are drug nano-carriers that are capable of targeting therapeutics to tumor sites because of enhanced permeability retention (EPR). In several preclinical studies with various tumor-bearing mice models, ¹⁸⁸Re-liposome that has been developed by the Institute of Nuclear Energy Research (INER) demonstrates favorable in vivo tumor targeting, biodistribution, pharmacokinetics, and dosimetry. It inhibits the growth of tumors, increased survival, demonstrates good synergistic combination, and was safe to use.

This study conducts a phase 0 low-radioactivity clinical trial of nano-targeted radiotherapeutics ¹⁸⁸Re-liposome to evaluate the effectiveness with which it targets tumors and the pharmacokinetics, biodistribution, dosimetry, and its safety in use. Twelve patients with metastatic cancers are studied in this trial. Serial whole-body scans and SPECT/CT are taken at 1, 4, 8, 24, 48, and 72 h after intravenous injection of 111 MBq of ¹⁸⁸Re-liposome. The effectiveness with which tumors are targeted, the pharmacokinetics, biodistribution, dosimetry, and safety are evaluated using the VelocityAI and OLINDA/EXM software. Blood samples are collected at different time points for a pharmacokinetics study and a safety evaluation that involves monitoring changes in liver, renal, and hematological functions.

Results

The T_½z for ¹⁸⁸Re-liposome in blood and plasma are 36.73 ± 14.00 h and 52.02 ± 45.21 h, respectively. The doses of radiation that are absorbed to vital organs such as the liver, spleen, lung, kidney, and bone marrow are 0.92 ± 0.35, 1.38 ± 1.81, 0.58 ± 0.28, 0.32 ± 0.09, and 0.06 ± 0.01 mGy/MBq, respectively, which is far less than the reference maximum tolerance dose after injection of ¹⁸⁸Re-liposome. ¹⁸⁸Re-liposome is absorbed by metastatic tumor lesions and the normal reticuloendothelial (RES) system. Certain patients exhibit a therapeutic response.

Conclusion

This phase 0 exploratory IND study shows that nanocarrier ¹⁸⁸Re-liposome achieves favorable tumor accumulation and tumor to normal organ uptake ratios for a subset of cancer patients. The clinical pharmacokinetic, biodistribution, and dosimetry results justify a further dose-escalating phase 1 clinical trial.

Trial registration

Taiwan FDA MA1101G0 (Jan 31, 2012).

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Title: A phase 0 study of the pharmacokinetics, biodistribution, and dosimetry of 188Re-liposome in patients with metastatic tumors
Authors: Shyh-Jen Wang
Wen-Sheng Huang
Chi-Mu Chuang
Chih-Hsien Chang
Te-Wei Lee
Gann Ting
Ming-Huang Chen
Peter Mu-Hsin Chang
Ta-Chung Chao
Hao-Wei Teng
Yee Chao
Yuh-Min Chen
Tzu-Ping Lin
Ya-Jen Chang
Su-Jung Chen
Yuan-Ruei Huang
Keng-Li Lan
Publication date: 01-12-2019
Publisher: Springer Berlin Heidelberg
Keyword: Pharmacokinetics
Published in: EJNMMI Research / Issue 1/2019
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-019-0509-6

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

A phase 0 study of the pharmacokinetics, biodistribution, and dosimetry of ¹⁸⁸Re-liposome in patients with metastatic tumors

Abstract

Background

Results

Conclusion

Trial registration

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Results

Conclusion

Trial registration

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