MEET US THE ANNUAL BOULDER PEPTIDE SYMPOSIUM
PEPTIDES IN MOLECULAR IMAGING AND NUCLEAR MEDICINE
Molecular imaging probes are important tools in nuclear medicine. Early disease detection, characterization and monitoring of disease progression and therapeutic responses are the main applications.
The use of imaging probes based on radiolabeled small molecules or macromolecules has been limited by low specificity (small molecules) or limited target permeability (monoclonal antibodies). Peptides have been increasingly considered as imaging probes, due to their distinctive advantages over small molecules or macromolecules. Peptides can act as a radionuclide carrier in Peptide Receptor Radionuclide Therapy (PRRT).
Due to their ability to bind to different receptors and also being part of several biochemical pathways, peptides act as potential diagnostic tools and biomarkers in disease (e.g. cancer) progression. Peptide receptors such as somatostatin (SST), integrin, gastrin-releasing peptide (GRP), cholecystokinin (CCK), neurotensin (NT), glucagon-like peptide-1 (GLP-1), and neuropeptide-Y (NPY) receptors have been successfully identified and characterized for tumor receptor imaging. Additionally, a number of bioactive peptides and peptide hormones have been discovered through combinatorial peptide chemistry and phage display technology. Such peptides generally have high affinities and specificity for their target and are active at low nanomolar concentrations.
Design of peptide-based probes for targeting peptide receptors
Peptides could be directly or indirectly labeled with a wide range of imaging moieties by different chemistries for use as in vivo probes. Radionuclides attached to peptides have been employed for positron emission tomography (PET) or single photon emission computed tomography (SPECT). Near-infrared (NIR) fluorescent dyes or quantum dots attached to peptides can be used for optical imaging. Paramagnetic agents attached to peptides are used for magnetic resonance imaging (MRI). In all these techniques the role of the peptide is to carry the probe to the specific receptor target.
Most neuroendocrine tumors (NETs) feature a strong overexpression of somatostatin receptors, mainly of subtype 2 (sst2). Currently, five somatostatin receptor subtypes (sst) are known (sst1-5). The density of these receptors is vastly higher than on non-tumor tissue. Therefore, somatostatin receptors are attractive targets for delivery of radioactivity via radiolabeled somatostatin analogs. Introduced in the late 1980s, [111In-DTPA]-octreotide ([111In]-pentetreotide, OctreoScan®), the first available radiolabeled somatostatin analog, rapidly became the gold standard for diagnosis of sst-positive NETs. An octreotide scan or octreoscan is a type of scintigraphy used to find carcinoid and other types of tumors and to localize sarcoidosis. [111In-DTPA]-octreotide is a synthetic analog of somatostatin carrying a chelating moiety and radiolabeled with indium-111. Injected into a vein the tracer travels through the bloodstream. The radioactive octreotide attaches to tumor cells that have receptors for somatostatin. A radiation-measuring device detects the radioactive octreotide and produces images showing where the tumor is located in the body.
|Radiolabeled Peptide||Peptide Receptor||Indication|
|Nα-(1-deoxy-D-fructosyl)-Nε-(2-[18F]-fluoropropionyl)-Lys0,Tyr3-octreotate (18F-[Gluc-Lys]-TOCA)||SST-Somatostatin||Neuroendocrine tumors|
|[18F]-galacto-RGD||Integrin||Head and neck cancer|
|[99Tc]-Me2Gly-Ser-Cys-Gly-5Ava-Bombesin (7-14)([99Tc]-RP-527)||GRP||Breast cancer|
Figure 1: Chemical structure of DOTA-octreotate
Somatostatin agonists vary in receptor selectivity: Lanreotide shows high affinity for sst2 and somewhat less to sst5. Pasireotide, another SRIF agonist, binds less selectively and thus mimics the natural ligand more closely.
Bachem monograph Peptides in Cancer Research, 2012436 published by Global Marketing, Bachem Group (2015)
What is your official job title at Bachem?
My official title at Bachem is “Working student”.
How long have you been with Bachem?
I am almost two years with Bachem. Before Bachem I had different jobs.
Briefly, what do you do at Bachem?
I do many different things. Basically I help wherever I can. This makes my job interesting and diversified.
What is your academic background?
I will be an archaeologist in a few years.
How is the Marketing & Sales team partnering with their customers?
Trough good communication and always doing its best to fulfill and even excel the customers’ expectations.
What makes a perfect day for you?
A perfect day is a day without any kind of worries. Relaxed, happy, carefree.
Have you had any particular expectation when you came to Bachem and have these been fulfilled?
No, I didn’t have any. But I am very happy I got this job. It’s the best job a student can think of and Bachem is very flexible when I need more (or less) time for the University.
What do you do for fun?
Baking is one of my favorite occupations. I also do sports and I like reading.
What is your preferred peptide?
My favorite peptide is Ghrelin, because it regulates the sense for hunger.
Thank you very much Hélène.