68Ga-labelled exendin-3, a new agent for the detection of insulinomas with PET.
68Ga-labelled exendin-3, a new agent for the detection of insulinomas with PET.
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DOI：
10.1007/s00259-009-1363-y
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发表时间：
2010-07
影响因子：
9.1
通讯作者：
Boerman, Otto C.
中科院分区：
文献类型：
--
作者：
Brom, Maarten;Oyen, Wim J. G.;Joosten, Lieke;Gotthardt, Martin;Boerman, Otto C.
胰岛素瘤是源自胰腺β细胞的神经内分泌肿瘤。胰高血糖素样肽1受体（GLP-1 R）在胰岛素瘤中的表达率高（>90%）且密度高。胰高血糖素样肽1（GLP-1），GLP-1 R的天然配体，在体内迅速降解。更稳定的GLP-1 R激动剂是毒蜥外泌肽-3。我们研究了胰岛素瘤与DOTA共轭exendin-3标记68 Ga的成像。在体外使用胰岛素瘤肿瘤细胞（INS-1）研究了用111 In或68 Ga标记的[Lys 40（DOTA）]毒蜥外泌肽-3靶向胰岛素瘤。[Lys 40（111 In-DTPA）]Exendin-3在本研究中用作参比品。在具有皮下INS-1肿瘤的BALB/c裸鼠中研究了体内靶向。使用临床前PET/CT扫描仪进行PET成像。在体外exendin-3特异性结合并被GLP-1 R阳性细胞内化。在具有皮下INS-1肿瘤的BALB/c裸鼠中，观察到肿瘤中[Lys 40（111 In-DTPA）]exendin-3的高摄取（注射后4 h为33.5 ± 11.6%ID/g）。通过共注射过量未标记的[Lys 40]exendin-3（1.8 ± 0.1%ID/g）测定，摄取具有特异性。胰腺也表现出高特异性摄取（11.3 ± 1.0%ID/g）。在肾脏中也发现了高摄取（144 ± 24%ID/g），并且这种摄取不是受体介导的。在该鼠肿瘤模型中，在毒蜥外泌肽剂量≤0.1 µg时获得了表达GLP-1 R的肿瘤的最佳靶向性。值得注意的是，68 Ga标记的[Lys 40（DOTA）]毒蜥外泌肽-3的肿瘤摄取（8.9 ± 3.1%ID/g）低于111 In标记的[Lys 40（DTPA）]毒蜥外泌肽-3的肿瘤摄取（25.4 ± 7.2%ID/g）。注射3 MBq [Lys 40（68 Ga-DOTA）]exendin-3后，通过小动物PET成像可以清楚地观察到皮下肿瘤。[Lys 40（68 Ga-DOTA）]毒蜥外泌肽-3在胰岛素瘤中特异性蓄积，尽管摄取低于[Lys 40（111 In-DTPA）]毒蜥外泌肽-3。因此，[Lys 40（68 Ga-DOTA）]exendin-3是用PET可视化胰岛素瘤的有前景的示踪剂。
Insulinomas are neuroendocrine tumours derived from pancreatic β-cells. The glucagon-like peptide 1 receptor (GLP-1R) is expressed with a high incidence (>90%) and high density in insulinomas. Glucagon-like peptide 1 (GLP-1), the natural ligand of GLP-1R, is rapidly degraded in vivo. A more stable agonist of GLP-1R is exendin-3. We investigated imaging of insulinomas with DOTA-conjugated exendin-3 labelled with 68Ga. Targeting of insulinomas with [Lys40(DOTA)]exendin-3 labelled with either 111In or 68Ga was investigated in vitro using insulinoma tumour cells (INS-1). [Lys40(111In-DTPA)]Exendin-3 was used as a reference in this study. In vivo targeting was investigated in BALB/c nude mice with subcutaneous INS-1 tumours. PET imaging was performed using a preclinical PET/CT scanner. In vitro exendin-3 specifically bound and was internalized by GLP-1R-positive cells. In BALB/c nude mice with subcutaneous INS-1 tumours a high uptake of [Lys40(111In-DTPA)]exendin-3 in the tumour was observed (33.5 ± 11.6%ID/g at 4 h after injection). Uptake was specific, as determined by coinjection of an excess of unlabelled [Lys40]exendin-3 (1.8 ± 0.1%ID/g). The pancreas also exhibited high and specific uptake (11.3 ± 1.0%ID/g). High uptake was also found in the kidneys (144 ± 24%ID/g) and this uptake was not receptor-mediated. In this murine tumour model optimal targeting of the GLP-1R expressing tumour was obtained at exendin doses ≤0.1 µg. Remarkably, tumour uptake of 68Ga-labelled [Lys40(DOTA)]exendin-3 was lower (8.9 ± 3.1%ID/g) than tumour uptake of 111In-labelled [Lys40(DTPA)]exendin-3 (25.4 ± 7.2%ID/g). The subcutaneous tumours were clearly visualized by small-animal PET imaging after injection of 3 MBq of [Lys40(68Ga-DOTA)]exendin-3. [Lys40(68Ga-DOTA)]Exendin-3 specifically accumulates in insulinomas, although the uptake is lower than that of [Lys40(111In-DTPA)]exendin-3. Therefore, [Lys40(68Ga-DOTA)]exendin-3 is a promising tracer to visualize insulinomas with PET.
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DOI：
10.1007/s00259-007-0604-1
发表时间：
2008-02-01
影响因子：
9.1
作者：
Laverman, Peter;Roosenburg, Susan;Boerman, Otto C.
通讯作者：
Boerman, Otto C.
DOI：
10.1007/s00259-007-0450-1
发表时间：
2007-10-01
影响因子：
9.1
作者：
Buchmann, I.;Henze, M.;Haberkorn, U.
通讯作者：
Haberkorn, U.
DOI：
10.1007/s00259-002-0761-1
发表时间：
2002-05-01
影响因子：
9.1
作者：
Gotthardt, M;Fischer, M;Behr, TM
通讯作者：
Behr, TM
DOI：
10.1007/s00259-004-1702-y
发表时间：
2005-04-01
影响因子：
9.1
作者：
Breeman, WAP;de Jong, M;Krenning, EP
通讯作者：
Krenning, EP
DOI：
10.1007/s00259-006-0317-x
发表时间：
2007-07-01
影响因子：
9.1
作者：
Antunes, P.;Ginj, M.;Maecke, H.
通讯作者：
Maecke, H.