Abstract
Gastrin-releasing peptide receptor (GRPR) is overexpressed by a variety of human tumors and in particular, identified to be upregulated in prostate cancers. The current study aimed to develop clinically translatable BBN analogue-based radioligands for positron emission tomography (PET) of GRPR-positive tumors. We developed radiolabeled BBN analogues and modified radiolabeled galacto-BBN analogues and then investigated their tumor-targeting efficacy in vivo. The chelator 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA) was used to radiolabel the peptides with 64Cu. The peptides were evaluated by measuring cell-based receptor-binding affinities. Biodistribution experiments and small animal imaging using PET were performed in nude mice bearing subcutaneous PC3 human prostate cancer xenografts. The conjugates were radiolabeled with yields >99%. The stability assay showed that [64Cu]NODAGA-BBN and [64Cu]NODAGA-galacto-BBN remained stable in both human and mouse serum for 1 h at 37°C. PET images of PC3 tumor-bearing nude mice were acquired at 1, 3, 24, 48 and 72 h after injection. [64Cu]NODAGA-galacto-BBN showed retention in tumors for 72 h, low liver uptake, and rapid renal clearance. PET imaging results were also confirmed by biodistrubution 1 and 3 h after injection. [64Cu]NODAGA-BBN and [64Cu]NODAGA-galacto-BBN are promising new PET probes for GRPR-positive prostate cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 1159-1168 |
| Number of pages | 10 |
| Journal | International Journal of Oncology |
| Volume | 46 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2015 Mar 1 |
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Keywords
- Cu
- Bombesin
- Positron emission tomography
- Prostate cancer
- Radiopharmaceuticals
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Evaluation of a 64Cu-labeled 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA)-galactose-bombesin analogue as a PET imaging probe in a gastrin-releasing peptide receptor-expressing prostate cancer xenograft model. / Kim, Min Hwan; Park, Ji Ae; Woo, Sang Keun; Lee, Kyo Chul; An, Gwang Il; Kim, Byoung Soo; Kim, Kwang Il; Lee, Tae Sup; Kim, Chan Wha; Kim, Kyeong Min; Kang, Joo Hyun; Lee, Yong Jin.
In: International Journal of Oncology, Vol. 46, No. 3, 01.03.2015, p. 1159-1168.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evaluation of a 64Cu-labeled 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA)-galactose-bombesin analogue as a PET imaging probe in a gastrin-releasing peptide receptor-expressing prostate cancer xenograft model
AU - Kim, Min Hwan
AU - Park, Ji Ae
AU - Woo, Sang Keun
AU - Lee, Kyo Chul
AU - An, Gwang Il
AU - Kim, Byoung Soo
AU - Kim, Kwang Il
AU - Lee, Tae Sup
AU - Kim, Chan Wha
AU - Kim, Kyeong Min
AU - Kang, Joo Hyun
AU - Lee, Yong Jin
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Gastrin-releasing peptide receptor (GRPR) is overexpressed by a variety of human tumors and in particular, identified to be upregulated in prostate cancers. The current study aimed to develop clinically translatable BBN analogue-based radioligands for positron emission tomography (PET) of GRPR-positive tumors. We developed radiolabeled BBN analogues and modified radiolabeled galacto-BBN analogues and then investigated their tumor-targeting efficacy in vivo. The chelator 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA) was used to radiolabel the peptides with 64Cu. The peptides were evaluated by measuring cell-based receptor-binding affinities. Biodistribution experiments and small animal imaging using PET were performed in nude mice bearing subcutaneous PC3 human prostate cancer xenografts. The conjugates were radiolabeled with yields >99%. The stability assay showed that [64Cu]NODAGA-BBN and [64Cu]NODAGA-galacto-BBN remained stable in both human and mouse serum for 1 h at 37°C. PET images of PC3 tumor-bearing nude mice were acquired at 1, 3, 24, 48 and 72 h after injection. [64Cu]NODAGA-galacto-BBN showed retention in tumors for 72 h, low liver uptake, and rapid renal clearance. PET imaging results were also confirmed by biodistrubution 1 and 3 h after injection. [64Cu]NODAGA-BBN and [64Cu]NODAGA-galacto-BBN are promising new PET probes for GRPR-positive prostate cancer.
AB - Gastrin-releasing peptide receptor (GRPR) is overexpressed by a variety of human tumors and in particular, identified to be upregulated in prostate cancers. The current study aimed to develop clinically translatable BBN analogue-based radioligands for positron emission tomography (PET) of GRPR-positive tumors. We developed radiolabeled BBN analogues and modified radiolabeled galacto-BBN analogues and then investigated their tumor-targeting efficacy in vivo. The chelator 1,4,7-triazacyclononane, 1-glutaric acid-4,7 acetic acid (NODAGA) was used to radiolabel the peptides with 64Cu. The peptides were evaluated by measuring cell-based receptor-binding affinities. Biodistribution experiments and small animal imaging using PET were performed in nude mice bearing subcutaneous PC3 human prostate cancer xenografts. The conjugates were radiolabeled with yields >99%. The stability assay showed that [64Cu]NODAGA-BBN and [64Cu]NODAGA-galacto-BBN remained stable in both human and mouse serum for 1 h at 37°C. PET images of PC3 tumor-bearing nude mice were acquired at 1, 3, 24, 48 and 72 h after injection. [64Cu]NODAGA-galacto-BBN showed retention in tumors for 72 h, low liver uptake, and rapid renal clearance. PET imaging results were also confirmed by biodistrubution 1 and 3 h after injection. [64Cu]NODAGA-BBN and [64Cu]NODAGA-galacto-BBN are promising new PET probes for GRPR-positive prostate cancer.
KW - Cu
KW - Bombesin
KW - Positron emission tomography
KW - Prostate cancer
KW - Radiopharmaceuticals
UR - http://www.scopus.com/inward/record.url?scp=84921926434&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84921926434&partnerID=8YFLogxK
U2 - 10.3892/ijo.2015.2832
DO - 10.3892/ijo.2015.2832
M3 - Article
C2 - 25586565
AN - SCOPUS:84921926434
VL - 46
SP - 1159
EP - 1168
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 3
ER -