Preclinical evaluation of (111)In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer.
(2014) In American journal of nuclear medicine and molecular imaging 4(4). p.311-323- Abstract
- The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the (111)In-labeled human internalizing antibody, INCA-X ((111)In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of (111)In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours... (More)
- The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the (111)In-labeled human internalizing antibody, INCA-X ((111)In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of (111)In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours post-injection of labeled DTPA-INCA-X. Biodistribution of the labeled antibody showed enriched activity in tumor, spleen and liver. Animals pre-administered with DTPA-INCA-X showed increased tumor uptake and blood content of (111)In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the (111)In-labeled INCA-X antibody is internalized into prostate cancer cells and by pre-administering non-labeled DTPA-INCA-X, we were able to significantly reduce the off target binding and increase the (111)In-DTPA-INCA-X mAb uptake in PC-3, PC-3M-Lu2 and DU145 xenografts. The results are encouraging and identifying the Ku70/Ku80 antigen as a target is worth further investigation for functional imaging of prostate cancer. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4583772
- author
- Evans Axelsson, Susan LU ; Vilhelmsson Timmermand, Oskar LU ; Welinder, Charlotte LU ; Borrebaeck, Carl Ak ; Strand, Sven-Erik LU ; Tran, Thuy LU ; Jansson, Bo LU and Bjartell, Anders LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- American journal of nuclear medicine and molecular imaging
- volume
- 4
- issue
- 4
- pages
- 311 - 323
- publisher
- e-Century Publishing
- external identifiers
-
- pmid:24982817
- ISSN
- 2160-8407
- language
- English
- LU publication?
- yes
- id
- 25a5d825-7a63-47ed-9548-089ed98a2e5d (old id 4583772)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24982817?dopt=Abstract
- date added to LUP
- 2016-04-04 09:15:02
- date last changed
- 2020-02-08 02:24:35
@article{25a5d825-7a63-47ed-9548-089ed98a2e5d, abstract = {{The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the (111)In-labeled human internalizing antibody, INCA-X ((111)In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of (111)In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours post-injection of labeled DTPA-INCA-X. Biodistribution of the labeled antibody showed enriched activity in tumor, spleen and liver. Animals pre-administered with DTPA-INCA-X showed increased tumor uptake and blood content of (111)In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the (111)In-labeled INCA-X antibody is internalized into prostate cancer cells and by pre-administering non-labeled DTPA-INCA-X, we were able to significantly reduce the off target binding and increase the (111)In-DTPA-INCA-X mAb uptake in PC-3, PC-3M-Lu2 and DU145 xenografts. The results are encouraging and identifying the Ku70/Ku80 antigen as a target is worth further investigation for functional imaging of prostate cancer.}}, author = {{Evans Axelsson, Susan and Vilhelmsson Timmermand, Oskar and Welinder, Charlotte and Borrebaeck, Carl Ak and Strand, Sven-Erik and Tran, Thuy and Jansson, Bo and Bjartell, Anders}}, issn = {{2160-8407}}, language = {{eng}}, number = {{4}}, pages = {{311--323}}, publisher = {{e-Century Publishing}}, series = {{American journal of nuclear medicine and molecular imaging}}, title = {{Preclinical evaluation of (111)In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer.}}, url = {{https://lup.lub.lu.se/search/files/5272857/5159788.pdf}}, volume = {{4}}, year = {{2014}}, }