| Title |
Targeted scVEGF/177Lu radiopharmaceutical inhibits growth of metastases and can be effectively combined with chemotherapy
|
|---|---|
| Published in |
EJNMMI Research, January 2016
|
| DOI | 10.1186/s13550-016-0163-1 |
| Pubmed ID | |
| Authors |
Mary Rusckowski, Yuzhen Wang, Francis G. Blankenberg, Zoia Levashova, Marina V. Backer, Joseph M. Backer |
| Abstract |
scVEGF/(177)Lu is a novel radiopharmaceutical targeted by recombinant single-chain (sc) derivative of vascular endothelial growth factor (VEGF) that binds to and is internalized by vascular endothelial growth factor receptors (VEGFR). scVEGF/(177)Lu potential as adjuvant and neoadjuvant anti-angiogenic therapy was assessed in metastatic and orthotopic mouse models of triple-negative breast cancer. Metastatic lesions in Balb/c mice were established by intracardiac injection of luciferase-expressing 4T1luc mouse breast carcinoma cells. Mice with metastatic lesions received single intravenous (i.v.) injection of well-tolerated dose of scVEGF/(177)Lu (7.4 MBq/mouse) at day 8 after 4T1luc cell injection. Primary orthotopic breast tumors in immunodeficient mice were established by injecting luciferase-expressing MDA231luc human breast carcinoma cells into mammary fat pad. Tumor-bearing mice were treated with single injections of scVEGF/(177)Lu (7.4 MBq/mouse, i.v), or liposomal doxorubicin (Doxil, 1 mg doxorubicin per kg, i.v.), or with a combination of Doxil and scVEGF/(177)Lu given at the same doses, but two hours apart. "Cold" scVEGF-targeting conjugate was included in controls and in Doxil alone group. The effects of treatments were defined by bioluminescent imaging (BLI), computed tomography (CT), computed microtomography (microCT), measurements of primary tumor growth, and immunohistochemical analysis. In metastatic model, adjuvant treatment with scVEGF/(177)Lu decreased overall metastatic burden and improved survival. In orthotopic primary tumor model, a combination of Doxil and scVEGF/(177)Lu was more efficient in tumor growth inhibition than each treatment alone. scVEGF/(177)Lu treatment decreased immunostaining for VEGFR-1, VEGFR-2, and pro-tumorigenic M2-type macrophage marker CD206. Selective targeting of VEGFR with well-tolerated doses of scVEGF/(177)Lu is effective in metastatic and primary breast cancer models and can be combined with chemotherapy. As high level of VEGFR expression is a common feature in a variety of cancers, targeted delivery of (177)Lu for specific receptor-mediated uptake warrants further exploration. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 29 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 21% |
| Student > Master | 4 | 14% |
| Other | 3 | 10% |
| Student > Doctoral Student | 3 | 10% |
| Student > Ph. D. Student | 3 | 10% |
| Other | 6 | 21% |
| Unknown | 4 | 14% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 28% |
| Chemistry | 3 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 10% |
| Biochemistry, Genetics and Molecular Biology | 3 | 10% |
| Agricultural and Biological Sciences | 2 | 7% |
| Other | 5 | 17% |
| Unknown | 5 | 17% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 January 2016.
All research outputs
#18,436,183
of 22,840,638 outputs
Outputs from EJNMMI Research
#335
of 557 outputs
Outputs of similar age
#283,813
of 392,526 outputs
Outputs of similar age from EJNMMI Research
#5
of 9 outputs
Altmetric has tracked 22,840,638 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 557 research outputs from this source. They receive a mean Attention Score of 2.5. This one is in the 30th percentile – i.e., 30% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 392,526 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 9 others from the same source and published within six weeks on either side of this one. This one has scored higher than 4 of them.