4 research outputs found
Hybrid Bombesin Analogues: Combining an Agonist and an Antagonist in Defined Distances for Optimized Tumor Targeting
Radiolabeled
hybrid ligands with defined distances between an agonist
and an antagonist for the gastrin-releasing peptide receptor were
found to have excellent tumor-targeting properties. Oligoprolines
served as rigid scaffolds that allowed for tailoring distances of
10, 20, and 30 Ă… between the recognition elements. In vitro and
in vivo studies revealed that the hybrid ligand with a distance of
20 Ă… between the recognition elements exhibits the highest yet
observed tumor cell uptake and retention time in prostate cancer cells
Additional file 2 of CUDC-907, a dual PI3K/histone deacetylase inhibitor, increases meta-iodobenzylguanidine uptake (123/131I-mIBG) in vitro and in vivo: a promising candidate for advancing theranostics in neuroendocrine tumors
Additional file 2. Additional data
New Gastrin Releasing Peptide Receptor-Directed [<sup>99m</sup>Tc]Demobesin 1 Mimics: Synthesis and Comparative Evaluation
We have previously reported on the
gastrin releasing peptide receptor (GRPR) antagonist [<sup>99m</sup>Tc]<b>1</b>, ([<sup>99m</sup>Tc]Âdemobesin 1, <sup>99m</sup>Tc-[N<sub>4</sub>′-diglycolate-dPhe<sup>6</sup>,Leu-NHEt<sup>13</sup>]ÂBBNÂ(6–13)). [<sup>99m</sup>Tc]<b>1</b> has
shown superior biological profile compared to analogous agonist-based <sup>99m</sup>Tc-radioligands. We herein present a small library of [<sup>99m</sup>Tc]<b>1</b> mimics generated after structural modifications
in (a) the linker ([<sup>99m</sup>Tc]<b>2</b>, [<sup>99m</sup>Tc]<b>3</b>, [<sup>99m</sup>Tc]<b>4</b>), (b) the peptide
chain ([<sup>99m</sup>Tc]<b>5</b>, [<sup>99m</sup>Tc]<b>6</b>), and (c) the C-terminus ([<sup>99m</sup>Tc]<b>7</b> or [<sup>99m</sup>Tc]<b>8</b>). The effects of above modifications on
the biological properties of analogs were studied in PC-3 cells and
tumor-bearing SCID mice. All analogs showed subnanomolar affinity
for the human GRPR, while most receptor-affine <b>4</b> and <b>8</b> behaved as potent GRPR antagonists in a functional internalization
assay. In mice bearing PC-3 tumors, [<sup>99m</sup>Tc]<b>1</b>–[<sup>99m</sup>Tc]<b>6</b> exhibited GRPR-specific
tumor uptake, rapidly clearing from normal tissues. [<sup>99m</sup>Tc]<b>4</b> displayed the highest tumor uptake (28.8 ±
4.1%ID/g at 1 h pi), which remained high even after 24 h pi (16.3
± 1.8%ID/g), well surpassing that of [<sup>99m</sup>Tc]<b>1</b> (5.4 ± 0.7%ID/g at 24 h pi)
New Gastrin Releasing Peptide Receptor-Directed [<sup>99m</sup>Tc]Demobesin 1 Mimics: Synthesis and Comparative Evaluation
We have previously reported on the
gastrin releasing peptide receptor (GRPR) antagonist [<sup>99m</sup>Tc]<b>1</b>, ([<sup>99m</sup>Tc]Âdemobesin 1, <sup>99m</sup>Tc-[N<sub>4</sub>′-diglycolate-dPhe<sup>6</sup>,Leu-NHEt<sup>13</sup>]ÂBBNÂ(6–13)). [<sup>99m</sup>Tc]<b>1</b> has
shown superior biological profile compared to analogous agonist-based <sup>99m</sup>Tc-radioligands. We herein present a small library of [<sup>99m</sup>Tc]<b>1</b> mimics generated after structural modifications
in (a) the linker ([<sup>99m</sup>Tc]<b>2</b>, [<sup>99m</sup>Tc]<b>3</b>, [<sup>99m</sup>Tc]<b>4</b>), (b) the peptide
chain ([<sup>99m</sup>Tc]<b>5</b>, [<sup>99m</sup>Tc]<b>6</b>), and (c) the C-terminus ([<sup>99m</sup>Tc]<b>7</b> or [<sup>99m</sup>Tc]<b>8</b>). The effects of above modifications on
the biological properties of analogs were studied in PC-3 cells and
tumor-bearing SCID mice. All analogs showed subnanomolar affinity
for the human GRPR, while most receptor-affine <b>4</b> and <b>8</b> behaved as potent GRPR antagonists in a functional internalization
assay. In mice bearing PC-3 tumors, [<sup>99m</sup>Tc]<b>1</b>–[<sup>99m</sup>Tc]<b>6</b> exhibited GRPR-specific
tumor uptake, rapidly clearing from normal tissues. [<sup>99m</sup>Tc]<b>4</b> displayed the highest tumor uptake (28.8 ±
4.1%ID/g at 1 h pi), which remained high even after 24 h pi (16.3
± 1.8%ID/g), well surpassing that of [<sup>99m</sup>Tc]<b>1</b> (5.4 ± 0.7%ID/g at 24 h pi)