Contact

Porträt Dr. Wodtke, Robert; FWPR

Dr. Robert Wodtke

PostDoc Researcher
Radionuclide Theragnostics
r.wodtkeAthzdr.de
Phone: +49 351 260 4033
+49 351 260 3923
+49 351 260 4070

Dr. Hans-Jürgen Pietzsch

Department Head
Radionuclide Theragnostics
h.j.pietzschAthzdr.de
Phone: +49 351 260 2706

Multi-targeted Radiotheranostics

Group Members

Dr. Robert Wodtke (Gruppenleiter)   ORCID

Florian Brandt, Dipl.-Pharm. (Doktorand)

Natalie Brenner (technische Mitarbeiterin)


We work closely on the following research topics with the departments of Radiopharmaceutical and Chemical Biology (Head Prof. Jens Pietzsch) and Radioimmunology (Head Dr. Anja Feldmann).

Additional targeting of albumin

Foto: Albuminbindende Radioliganden auf dem Weg zum Tumor ©Copyright: Dr. Robert Wodtke

Albumin-binding radioligands on their way to the tumor

Source: Dr. Wodtke, Robert

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Albumin is the most abundant protein in the blood with a concentration of around 40 g/L (600 µM at a molecular weight of 67 000 g/mol). It exhibits an extraordinary long half-time of around 19 days due to a natural recycling mechanism. Albumin serves as a carrier protein for a variety of molecules, including fatty acids, metal ions and drugs. The binding properties of albumin are exploited for the pharmacokinetic optimization of drugs. One prominent example is Levemir® (Insulin detemir), an insulin analogue for people with diabetes type I and II, which is modified with myristic acid. The modification with this fatty acid enables a good binding to albumin, resulting in a long blood circulation time and thus, a prolonged effect on the blood glucose level.

The principle of conscious binding to albumin has also entered the methodology for pharmacokinetic optimization of radiopharmaceuticals, in particular endoradiotherapeutic agents. Tumors can exhibit an increased uptake of albumin to satisfy the demand of the growing malignant tissue for amino acids. Furthermore, albumin can accumulate in the tumor tissue due to leaky blood vessels (a phenomenon also known as enhanced permeability and retention – EPR effect). Both effects can be utilized by an additional albumin binding moiety in the endoradiotherapeutic agent to finally increase the deposited dose in the tumour. The aims by this strategy are on one side improvements of known endoradiotherapeutic agents and on the other side enabling the access to novel agents.

Regarding the albumin binding entity, the group focusses on Lys(IPB)-OH derivatives and searches for ways to modularly introduce this entity in a variety of molecules (small molecules, peptides, proteins). Currently, we test the modification of ligands of the somatostatin receptor typ II (SSTR2), such as Tyr3-octreotate. SSTR2 is highly expressed by gastroenteropancreatic neuroendocrine tumurs (GEP-NET) and represents an interesting target for diagnostic and therapeutic radiopharmaceuticals.

Additional targeting of neprilysin (CD10)

Foto: Aufbau eines zielgerichteten Radiopharmazeutikums mit Neprilysin-Spaltstelle ©Copyright: Dr. Robert Wodtke

Structure of a targeted radiopharmaceutical bearing a cleavage sequence for neprilysin

Source: Dr. Wodtke, Robert

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Neprilysin is a zinc(II)-dependent membrane-bound metalloprotease, which ubiquitously expressed in the human body, but particularly high in the kidneys. A limitation for endoradiotherapeutic approaches is often faced by a high radiation exposure of the kidneys as especially peptides (and also the radiolabeled analogues) are cleared from the body via the kidneys. This can lead to an undesired accumulation of the radioconjugate in the kidneys due to the reabsorption of the molecules mediated by megalin and cubilin receptors within the proximal tubule. Coupling of the radionuclide-chelator-complex via a cleavable sequence for Neprilysin enables a way to clear the radiolabel from the kidneys and thus reduce their radiation exposure. Based on known tripeptides from the literature, novel cleavable substrates for Neprilysin were developed and ways for the modular introduction into peptides/proteins investigated.

References


Areas of work

Peptide synthesis, organic synthesis, biochemical characterisation (assay development), radiosynthesis, radiopharmacological characterisation


Contact

Dr. Robert Wodtke

PostDoc Researcher
Radionuclide Theragnostics
r.wodtkeAthzdr.de
Phone: +49 351 260 4033
+49 351 260 3923
+49 351 260 4070

Dr. Hans-Jürgen Pietzsch

Department Head
Radionuclide Theragnostics
h.j.pietzschAthzdr.de
Phone: +49 351 260 2706