Unknown

Dataset Information

0

Companion Diagnostic 64Cu-Liposome Positron Emission Tomography Enables Characterization of Drug Delivery to Tumors and Predicts Response to Cancer Nanomedicines.


ABSTRACT: Deposition of liposomal drugs into solid tumors is a potentially rate-limiting step for drug delivery and has substantial variability that may influence probability of response. Tumor deposition is a shared mechanism for liposomal therapeutics such that a single companion diagnostic agent may have utility in predicting response to multiple nanomedicines. Methods: We describe the development, characterization and preclinical proof-of-concept of the positron emission tomography (PET) agent, MM-DX-929, a drug-free untargeted 100 nm PEGylated liposome stably entrapping a chelated complex of 4-DEAP-ATSC and 64Cu (copper-64). MM-DX-929 is designed to mimic the biodistribution of similarly sized therapeutic agents and enable quantification of deposition in solid tumors. Results: MM-DX-929 demonstrated sufficient in vitro and in vivo stability with PET images accurately reflecting the disposition of liposome nanoparticles over the time scale of imaging. MM-DX-929 is also representative of the tumor deposition and intratumoral distribution of three different liposomal drugs, including targeted liposomes and those with different degrees of PEGylation. Furthermore, stratification using a single pre-treatment MM-DX-929 PET assessment of tumor deposition demonstrated that tumors with high MM-DX-929 deposition predicted significantly greater anti-tumor activity after multi-cycle treatments with different liposomal drugs. In contrast, MM-DX-929 tumor deposition was not prognostic in untreated tumor-bearing xenografts, nor predictive in animals treated with small molecule chemotherapeutics. Conclusions: These data illustrate the potential of MM-DX-929 PET as a companion diagnostic strategy to prospectively select patients likely to respond to liposomal drugs or nanomedicines of similar molecular size.

SUBMITTER: Lee H 

PROVIDER: S-EPMC5928891 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

altmetric image

Publications

Companion Diagnostic <sup>64</sup>Cu-Liposome Positron Emission Tomography Enables Characterization of Drug Delivery to Tumors and Predicts Response to Cancer Nanomedicines.

Lee Helen H   Gaddy Daniel D   Ventura Manuela M   Bernards Nicholas N   de Souza Raquel R   Kirpotin Dmitri D   Wickham Thomas T   Fitzgerald Jonathan J   Zheng Jinzi J   Hendriks Bart S BS  

Theranostics 20180321 9


Deposition of liposomal drugs into solid tumors is a potentially rate-limiting step for drug delivery and has substantial variability that may influence probability of response. Tumor deposition is a shared mechanism for liposomal therapeutics such that a single companion diagnostic agent may have utility in predicting response to multiple nanomedicines. <b>Methods:</b> We describe the development, characterization and preclinical proof-of-concept of the positron emission tomography (PET) agent,  ...[more]

Similar Datasets

| S-EPMC2077283 | biostudies-literature
| S-EPMC5264522 | biostudies-literature
2015-02-09 | E-MTAB-3175 | biostudies-arrayexpress
2011-11-01 | GSE21217 | GEO
| S-EPMC2874192 | biostudies-literature
| S-EPMC4287963 | biostudies-literature
2020-03-18 | GSE131769 | GEO
2011-11-01 | E-GEOD-21217 | biostudies-arrayexpress
| S-EPMC11558499 | biostudies-literature
| S-EPMC8266729 | biostudies-literature