2013
DOI: 10.1002/anie.201303422
|View full text |Cite
|
Sign up to set email alerts
|

Positron Emission Tomography Imaging of Drug‐Induced Tumor Apoptosis with a Caspase‐Triggered Nanoaggregation Probe

Abstract: An 18F-labeled caspase-3 sensitive nano-aggregation PET tracer ([18F]CSNAT) was prepared and evaluated for imaging caspase-3 activity in doxorubicin-treated tumor xenografts. This enzyme-activatable PET tracer is designed to function in a novel mechanism – enhanced retention of the 18F activity in apoptotic tumors is achieved through intramolecular macrocyclization and in situ aggregation upon caspase-3 activation.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1

Citation Types

2
77
0

Year Published

2014
2014
2023
2023

Publication Types

Select...
7
1

Relationship

2
6

Authors

Journals

citations
Cited by 103 publications
(84 citation statements)
references
References 25 publications
2
77
0
Order By: Relevance
“…37−39 The lower r 1 value is presumably due to the flexibility of the linear oligomer of the scaffold after polymerization. In order to effectively out-compete free cysteine, we have optimized the self-assembly strategy by switching the concentration-dependent intermolecular polymerization to concentration-independent intramolecular macrocyclization chemistry, showing high efficacy to self-assemble fluorescence 40,41 and PET probes 42 into nanoparticles for imaging of enzyme activity in biological systems. This optimized self-assembly system can also be applied to develop the first example of caspase-3/7 activatable Gd-based MRI probe by introducing a Gd-DOTA amide chelate.…”
Section: Introductionmentioning
confidence: 99%
“…37−39 The lower r 1 value is presumably due to the flexibility of the linear oligomer of the scaffold after polymerization. In order to effectively out-compete free cysteine, we have optimized the self-assembly strategy by switching the concentration-dependent intermolecular polymerization to concentration-independent intramolecular macrocyclization chemistry, showing high efficacy to self-assemble fluorescence 40,41 and PET probes 42 into nanoparticles for imaging of enzyme activity in biological systems. This optimized self-assembly system can also be applied to develop the first example of caspase-3/7 activatable Gd-based MRI probe by introducing a Gd-DOTA amide chelate.…”
Section: Introductionmentioning
confidence: 99%
“…18 F-C-SNAT precursor (Supplemental Fig. 1; supplemental materials are available at http://jnm.snmjournals.org) was produced in-house as previously described (21). Mice (female nu/nu) were purchased from Charles River Laboratories, and all animal experiments were approved by the Stanford Administrative Panel on Laboratory Animal Care in compliance with all federal and state regulations governing the humane care and use of laboratory animals.…”
Section: Generalmentioning
confidence: 99%
“…Another class of PET tracers is based on caspase-3 inhibitors, one of which, 18 (17), has undergone evaluation in healthy humans (18); however, the tumor uptake in chemotherapeutictreated mice is also limited, with approximately 1 %ID/g maximum and significant treatment response reported only from a small subset of the tumor region (19). To generate better retention of the product in apoptotic cells, a novel class of tracers takes advantage of the cleavage activity of the effector enzyme caspase-3/7, including 18 F-CP-18 (20) and 18 F-C-SNAT (C-SNAT is caspase-sensitive nanoaggregation tracer) developed by us (21).…”
mentioning
confidence: 99%
See 1 more Smart Citation
“…For the radiosynthesis of 18 F-C-SNAT, Rao's group applied the tracer principle. 18 F-C-SNAT was prepared with high efficiency, labeling precursor was removed, and the amount of peptide could be kept low (1). Therefore, clinical translation can easily be realized by the microdosing concept (,100 mg), for which the necessary toxicology data can be determined quickly and inexpensively.…”
mentioning
confidence: 99%