Synthesis and Biological Evaluation of a Novel 177Lu-DOTA-[Gly3-Cyclized(Dap4, <scp>d</scp>-Phe7, Asp10)-Arg11]α-MSH3–13 Analogue for Melanocortin-1 Receptor-Positive Tumor Targeting

Lim, Jae Cheong; Hong, Young Don; Kim, Jin Ju; Choi, Sang Mu; Baek, Hye Suk; Choi, Sang-Jin

doi:10.1089/cbr.2011.1140

Cited by 4 publications

(2 citation statements)

References 18 publications

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“…There is a way to improve the stability through the cyclization of the peptide therein, which has been demonstrated in studies of the targeting peptide of melanoma. Thus, by the cyclic structure of the peptide CCK, it was confirmed targeting functionality and stability of this material (Lim et al, 2012).…”

Section: Discussionmentioning

confidence: 64%

“…Several methods have been studied to improve the stability of peptide in the blood (Ocak et al, 2011). A method for improving the reliability has been demonstrated in studies of the target peptide melanoma through cyclization of an internal peptide (Lim et al, 2012). Therefore, the stability and functionality of the cyclic structure of the CCK analogues are confirmed.…”

Section: Ojbsmentioning

confidence: 99%

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Cyclic Cholecystokinin Analogues Exhibit High Blood Stability and Binding Affinity With Cholecystokinin Receptor

Joh¹,

Lim²,

Kim³

et al. 2014

OnLine Journal of Biological Sciences

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Recently, incidence of Cholecystokinin (CCK) receptor is recognized as a factor that determines the aggressive phenotype of pancreatic cancer. In this study, a novel Cholecystokinin (CCK) analogues; DOTA-Nle-cyclo (Glu-Trp-Met-Asp-Phe-Lys-NH2) (DOTA-cCCK) and DOTA-Nle-cyclo (Glu-Trp-Nle-Asp-Phe-Lys-NH2) (DOTA-[Nle]-cCCK) were synthesized and radiolabeled and the targeting abilities on the CCK receptor were evaluated for new CCK receptor targeting agents searching. Peptides were prepared through a solid phase synthesis method and their purity was over 98%. DOTA is the chelating agent for 68Ga-labelling, which the peptides were radiolabeled with 68Ga by a high radiolabeling yield (>98%). Peptides were stable over 98% by incubation in mouse blood at 37°C for 2 h. A competitive displacement of 125I-CCK8 on the AR42J human pancreatic carcinoma cells revealed that 50% inhibitory concentration value (IC50) were 12.31 nM of DOTA-cCCK and 1.69 nM of DOTA-[Nle]-cCCK. Stable in the blood of both DOTA-cCCK and DOTA-[Nle]-cCCK, but the binding rate with the CCK receptor on AR42J cells, DOTA-[Nle]-cCCK confirmed better than DOTA-cCCK. Therefore, it is concluded that 68Ga-DOTA-[Nle]-cCCK can be potential candidate as a targeting modality for the CCK receptor over-expressing tumors and further studies to evaluate their biological characteristics are needed.

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Section: Discussionmentioning

confidence: 64%

Section: Ojbsmentioning

confidence: 99%

Cyclic Cholecystokinin Analogues Exhibit High Blood Stability and Binding Affinity With Cholecystokinin Receptor

Joh¹,

Lim²,

Kim³

et al. 2014

OnLine Journal of Biological Sciences

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Synthesis, Characterization, and Initial Biological Evaluation of [^99mTc]Tc‐Tricarbonyl‐labeled DPA‐α‐MSH Peptide Derivatives for Potential Melanoma Imaging

et al. 2018

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α-Melanocyte stimulating hormone (α-MSH) derivatives target the melanocortin-1 receptor (MC1R) specifically and selectively. In this study, the α-MSH-derived peptide NAP-NS1 (Nle-Asp-His-d-Phe-Arg-Trp-Gly-NH ) with and without linkers was conjugated with 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid (DPA-COOH) and labeled with [ Tc]Tc-tricarbonyl by two methods. With the one-pot method the labeling was faster than with the two-pot method, while obtaining similarly high yields. Negligible trans-chelation and high stability in physiological solutions was determined for the [ Tc]Tc-tricarbonyl-peptide conjugates. Coupling an ethylene glycol (EG)-based linker increased the hydrophilicity. The peptide derivatives displayed high binding affinity in murine B16F10 melanoma cells as well as in human MeWo and TXM13 melanoma cell homogenates. Preliminary in vivo studies with one of the [ Tc]Tc-tricarbonyl-peptide conjugates showed good stability in blood and both renal and hepatobiliary excretion. Biodistribution was performed on healthy rats to gain initial insight into the potential relevance of the Tc-labeled peptides for in vivo imaging.

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Radiopharmacological characterization of 64Cu-labeled α-MSH analogs for potential use in imaging of malignant melanoma

Gao

Sihver²,

Jurischka³

et al. 2015

Amino Acids

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The melanocortin-1 receptor (MC1R) plays an important role in melanoma growth, angiogenesis and metastasis, and is overexpressed in melanoma cells. α-Melanocyte stimulating hormone (α-MSH) and derivatives are known to bind with high affinity at this receptor that provides the potential for selective targeting of melanoma. In this study, one linear α-MSH-derived peptide Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH2 (NAP-NS1) without linker and with εAhx-β-Ala linker, and a cyclic α-MSH derivative, [Lys-Glu-His-D-Phe-Arg-Trp-Glu]-Arg-Pro-Val-NH2 (NAP-NS2) with εAhx-β-Ala linker were conjugated with p-SCN-Bn-NOTA and labeled with (64)Cu. Radiochemical and radiopharmacological investigations were performed with regard to transchelation, stability, lipophilicity and in vitro binding assays as well as biodistribution in healthy rats. No transchelation reactions, but high metabolic stability and water solubility were demonstrated. The linear derivatives showed higher affinity than the cyclic one. [(64)Cu]Cu-NOTA-εAhx-β-Ala-NAP-NS1 ([(64)Cu]Cu-2) displayed rapid cellular association and dissociation in murine B16F10 cell homogenate. All [(64)Cu]Cu-labeled conjugates exhibited affinities in the low nanomolar range in B16F10. [(64)Cu]Cu-2 showed also high affinity in human MeWo and TXM13 cell homogenate. In vivo studies suggested that [(64)Cu]Cu-2 was stable, with about 85 % of intact peptide in rat plasma at 2 h p.i. Biodistribution confirmed the renal pathway as the major elimination route. The uptake of [(64)Cu]Cu-2 in the kidney was 5.9 % ID/g at 5 min p.i. and decreased to 2.0 % ID/g at 60 min p.i. Due to the prospective radiochemical and radiopharmacological properties of the linear α-MSH derivative [(64)Cu]Cu-2, this conjugate is a promising candidate for tracer development in human melanoma imaging.

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Synthesis and Biological Evaluation of a Novel ¹⁷⁷Lu-DOTA-[Gly³-Cyclized(Dap⁴, _d-Phe⁷, Asp¹⁰)-Arg¹¹]α-MSH_3–13 Analogue for Melanocortin-1 Receptor-Positive Tumor Targeting

Cited by 4 publications

References 18 publications

Cyclic Cholecystokinin Analogues Exhibit High Blood Stability and Binding Affinity With Cholecystokinin Receptor

Cyclic Cholecystokinin Analogues Exhibit High Blood Stability and Binding Affinity With Cholecystokinin Receptor

Synthesis, Characterization, and Initial Biological Evaluation of [^99mTc]Tc‐Tricarbonyl‐labeled DPA‐α‐MSH Peptide Derivatives for Potential Melanoma Imaging

Radiopharmacological characterization of 64Cu-labeled α-MSH analogs for potential use in imaging of malignant melanoma

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Synthesis and Biological Evaluation of a Novel 177Lu-DOTA-[Gly3-Cyclized(Dap4, d-Phe7, Asp10)-Arg11]α-MSH3–13 Analogue for Melanocortin-1 Receptor-Positive Tumor Targeting

Cited by 4 publications

References 18 publications

Cyclic Cholecystokinin Analogues Exhibit High Blood Stability and Binding Affinity With Cholecystokinin Receptor

Cyclic Cholecystokinin Analogues Exhibit High Blood Stability and Binding Affinity With Cholecystokinin Receptor

Synthesis, Characterization, and Initial Biological Evaluation of [99mTc]Tc‐Tricarbonyl‐labeled DPA‐α‐MSH Peptide Derivatives for Potential Melanoma Imaging

Radiopharmacological characterization of 64Cu-labeled α-MSH analogs for potential use in imaging of malignant melanoma

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Product

Resources

About

Synthesis and Biological Evaluation of a Novel ¹⁷⁷Lu-DOTA-[Gly³-Cyclized(Dap⁴, _d-Phe⁷, Asp¹⁰)-Arg¹¹]α-MSH_3–13 Analogue for Melanocortin-1 Receptor-Positive Tumor Targeting

Synthesis, Characterization, and Initial Biological Evaluation of [^99mTc]Tc‐Tricarbonyl‐labeled DPA‐α‐MSH Peptide Derivatives for Potential Melanoma Imaging