Novel Chemically Modified Analogues of Neuropeptide Y for Tumor Targeting

Zwanziger, Denise; Khan, Irfan Ullah; Neundorf, Ines; Sieger, Stephanie; Lehmann, Lutz; Friebe, Matthias; Dinkelborg, Ludger; Beck‐Sickinger, Annette G.

doi:10.1021/bc7004297

Cited by 54 publications

(44 citation statements)

References 28 publications

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“…Peptide imaging agents can be used to visualize a range of targets, including integrins (20,57,294), matrix metalloproteinases (36,187), caspases (91,95), somatostatin receptors (82,136,331), neuropeptide Y receptor (253,485), and gastrin releasing peptide receptor (372,427,428). See TABLE 2 for some specific examples of peptide molecular imaging agents that can be used for optical, PET, and SPECT imaging.…”

Section: Peptidesmentioning

confidence: 99%

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

James

Gambhir

2012

Physiological Reviews

942

954

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Molecular imaging is revolutionizing the way we study the inner workings of the human body, diagnose diseases, approach drug design, and assess therapies. The field as a whole is making possible the visualization of complex biochemical processes involved in normal physiology and disease states, in real time, in living cells, tissues, and intact subjects. In this review, we focus specifically on molecular imaging of intact living subjects. We provide a basic primer for those who are new to molecular imaging, and a resource for those involved in the field. We begin by describing classical molecular imaging techniques together with their key strengths and limitations, after which we introduce some of the latest emerging imaging modalities. We provide an overview of the main classes of molecular imaging agents (i.e., small molecules, peptides, aptamers, engineered proteins, and nanoparticles) and cite examples of how molecular imaging is being applied in oncology, neuroscience, cardiology, gene therapy, cell tracking, and theranostics (therapy combined with diagnostics). A step-by-step guide to answering biological and/or clinical questions using the tools of molecular imaging is also provided. We conclude by discussing the grand challenges of the field, its future directions, and enormous potential for further impacting how we approach research and medicine.

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Section: Peptidesmentioning

confidence: 99%

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

James

Gambhir

2012

Physiological Reviews

942

954

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“…The group of Beck-Sickinger has been particularly active in developing Y 1 - and Y 2 -preferring radiotracers. Their most recent article reports on the synthesis and characterization of a large number of NPY analogs (20). A potent and well-characterized radiotracer is [Lys( 111 In-DOTA) 4 ,Phe 7 ,-Pro 34 ]-NPY.…”

Section: Npy Numerous Attractive Indications For Npy Radioligand Tarmentioning

confidence: 99%

Peptide-Based Probes for Cancer Imaging

Reubi¹,

Maecke²

2008

J Nucl Med

259

238

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Receptors for regulatory peptides are overexpressed in a variety of human cancers. They represent the molecular basis for in vivo imaging with radiolabeled peptide probes. Somatostatin-derived tracers, designed to image the sst 2 -overexpressing neuroendocrine tumors, have enjoyed almost 2 decades of successful development and extensive clinical applications. More recent developments include second-and third-generation somatostatin analogs, with a broader receptor subtype profile or with antagonistic properties. Emerging tracers for other peptide receptors, including cholecystokinin/gastrin and GLP-1 analogs for neuroendocrine tumors, bombesin and neuropeptide-Y analogs for prostate or breast cancers, or Arg-Gly-Asp peptides for neoangiogenesis labeling, are also in current development. Application fields include both SPECT/CT and PET/CT.

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“…[14] Time-dependent incubation showed halflives of 9.9 to 32 h; these values are in the same range or slightly reduced for the Y 1 receptor selective peptides compared to NPY (t 1/2 = 24.7 AE 1.4 h) (Figure 1 c). [15,16] For radiolabeling of the highly selective peptides 2 a and 2 b, an approved protocol [17][18][19] was used, yielding in 99m Tc V species, which are denoted 99m Tc(core) 3+ . Because the interaction between plasma proteins and peptides directly and indirectly affects different pharmacokinetic parameters, such as volume of distribution, metabolism and excretion of the drugs, and accordingly the dosage, [20] protein binding of 99m Tc(core) 3+ -labeled peptides 2 a and 2 b were studied in vitro in human blood at several time intervals and showed high stability of the formed 99m Tc(core) 3+ -peptide complex.…”

Section: In Memory Of Rainer Rudolphmentioning

confidence: 99%

Breast‐Cancer Diagnosis by Neuropeptide Y Analogues: From Synthesis to Clinical Application

et al. 2010

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In memory of Rainer RudolphBreast cancer is still one of the most frequently occurring tumors in women. Severe and often therapy-limiting side effects are a major obstacle in chemotherapy. New delivery concepts that reduce systemic side effects are needed to optimize anticancer therapies, and selective targeting concepts are required for early and selective tumor diagnosis. Neuropeptide Y (NPY), a member of the pancreatic polypeptide family, is a C-terminal amidated peptide hormone consisting of 36 amino acid residues.[1, 2] NPY-mediated functions are transmitted by so-called Y receptors, named Y 1 , Y 2 , and Y 5 receptors, which bind NPY with nanomolar affinity. All Y receptors are members of the class A of heptahelix receptors, that signal through heterotrimeric G proteins. [3,4] Reubi et al. have recently described Y-receptor expression in human breast cancer. They have shown that over 90 % of all breast tumors and 100 % of the examined metastases express Y 1 receptors.[5] Interestingly, a shift of the receptor subtype from Y 2 receptors in healthy tissue to Y 1 receptors during neoplasm was found, which is potentially related to reduced differentiation. Based on NPY and the known structure-activity relationships for Y 1 -receptor binding, [6] we designed, synthesized, and characterized two analogues for tumor labeling that vary in the position of the chelator to conjugate 99m Tc. Peptides 1 a and 2 a were synthesized with a N a -histidinyl acetyl (N a His-ac) chelator [7] at the N terminus, whereas peptides 1 b and 2 b were modified at the N e side chain of Lys 4 . The tridentate ligand N a His-ac is able to form stable and biologically active complexes. [8,9] Modification of the resin-bound peptide was performed by an efficient strategy (Scheme 1). In the first step, bromoacetic acid was activated by diisopropylcarbodiimide to form the corresponding anhydride. His(Trt)-OtBu was then added and the NHÀ CH bond was formed by HBr elimination. Cleavage of the peptide yielded His-acetyl peptides either at the N terminus or at the N e side chain of Lys 4 . Rhenium was used as a cold surrogate for 99m Tc and introduced for in vitro studies

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Novel Chemically Modified Analogues of Neuropeptide Y for Tumor Targeting

Cited by 54 publications

References 28 publications

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

Peptide-Based Probes for Cancer Imaging

Breast‐Cancer Diagnosis by Neuropeptide Y Analogues: From Synthesis to Clinical Application

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