Jens Pietzsch

• Ph.D., M.D., Prof.
• Head of Department at Helmholtz-Zentrum Dresden-Rossendorf

A current global limitation to the timely and equitable patient access to PSMA-based therapies for prostate cancer (PCa) is the insufficient PET capacity for pretreatment imaging. However, the extensive global availability of SPECT cameras renders this imaging technology as an attractive alternative. The lack of regulatory approved PSMA radioligand...

The cylcooxygenase isoforms COX‐1 and COX‐2 are involved in the production of prostaglandins in physiological and pathological processes. The overexpression of COX‐2 under inflammatory conditions as well as its role in cancer and neurodegenerative diseases necessitates the need to develop and improve non‐steroidal anti‐inflammatory drugs. These COX...

This study explores the anticancer potential of N‐methylated open‐ring derivatives of carborane‐substituted diclofenac analogs. By N‐methylation, the open‐chain form could be trapped and cyclization back to lactam or amidine derivatives is inhibited. A small library of carborane‐ and phenyl‐based secondary and tertiary arylamines bearing carboxylic...

The inducible enzyme cyclooxygenase-2 (COX-2) and the subsequent synthesis of eicosanoids initiated by this enzyme are important molecular players in bone healing. In this pilot study, the suitability of a novel selective COX-2 inhibitor bearing a nitric oxide (NO)-releasing moiety was investigated as a modulator of healing a critical-size bone def...

In this study, we investigated a novel anti-cancer drug design approach by revisiting diclofenac-based carborane-substituted prodrugs. The redesigned compounds combine the robust carborane scaffold with the oxindole framework, resulting in four carborane-derivatized oxindoles and a unique zwitterionic amidine featuring a nido-cluster. We tested the...

Supplemental data for: Ullrich M, Wodtke R, Brandt F, Freudenberg R, Kotzerke J, Richter S, Kopka K, Pietzsch J. The heterobivalent (SSTR2/albumin) radioligand [67Cu]Cu-NODAGA-cLAB4-TATE enables efficient somatostatin receptor radionuclide theranostics. Theranostics 2024; 14(14):5371-5387. doi:10.7150/thno.100091. https://www.thno.org/v14p5371.htm

The most effective anticancer drugs currently entail substantial and formidable side effects, and resistance of tumors to chemotherapeutic agents is a further challenge. Thus, the search for new anticancer drugs as well as novel therapeutic methods is still extremely important. Non‐steroidal anti‐inflammatory drugs (NSAIDs) can inhibit COX (cycloox...

Background/Objective Pancreatic stellate cells (PSCs) in pancreatic adenocarcinoma (PDAC) are producing extracellular matrix, which promotes the formation of a dense fibrotic microenvironment. This makes PDAC a highly heterogeneous tumor-stroma-driven entity, associated with reduced perfusion, limited oxygen supply, high interstitial fluid pressure...

The Al¹⁸F-labeling approach offers a one-step access to radiofluorinated biomolecules by mimicking the labeling process for radiometals. Although these labeling conditions are considered to be mild compared to classic radiofluorinations, improvements of the chelating units have led to the discovery of (±)-H3RESCA, which allows Al¹⁸F-labeling alread...

Somatostatin type 2 receptor (SSTR2) radionuclide therapy using β⁻ particle-emitting radioligands has entered clinical practice for the treatment of neuroendocrine neoplasms (NENs). Despite the initial success of [¹⁷⁷Lu]Lu‑DOTA-TATE, theranostic SSTR2 radioligands require improved pharmacokinetics and enhanced compatibility with alternative radionu...

Hydrogel‐based injectable drug delivery systems provide temporally and spatially controlled drug release with reduced adverse effects on healthy tissues. Therefore, they represent a promising therapeutic option for unresectable solid tumor entities. In this study, a peptide‐starPEG/hyaluronic acid‐based physical hydrogel is modified with ferrocene...

Discussed are two picolinate appended bispidine ligands (3,7‐diazabicyclo[3.3.1]nonane derivatives) in comparison with an earlier described bis‐pyridine derivative, which are all known to strongly bind CuII. The radiopharmacological characterization of the two isomeric bispidine complexes includes quantitative labeling with ⁶⁴CuII at ambient condit...

The extracellular environment regulates the structures and functions of cells, from the molecular to the tissue level. However, the underlying mechanisms influencing the organization and adaptation of cancer in three‐dimensional (3D) environments are not yet fully understood. In this study, the influence of the viscosity of the environment is inves...

Background Transglutaminase 2 (TGase 2) is a multifunctional protein and has a prominent role in various (patho)physiological processes. In particular, its transamidase activity, which is rather latent under physiological conditions, gains importance in malignant cells. Thus, there is a great need of theranostic probes for targeting tumor-associate...

Radionuclide therapies are an important tool for the management of patients with neuroendocrine neoplasms (NENs). Especially [¹³¹I]MIBG and [¹⁷⁷Lu]Lu-DOTA-TATE are routinely used for the treatment of a subset of NENs, including pheochromocytomas, paragangliomas and gastroenteropancreatic tumors. Some patients suffering from other forms of NENs, suc...

Extracellular environment regulates structures and functions of cells, from molecular up to the tissue level. However, underlying mechanisms that influence organization and adaptation of cancer in 3D environments are not yet fully understood. In this study, we investigate the influence of viscosity of the environment on the mechanical adaptability...

Glioma are clinically challenging tumors due to their location and invasiveness nature, which often hinder complete surgical resection. The evaluation of the isocitrate dehydrogenase mutation status has become crucial for effective patient stratification. Through a transdisciplinary approach, we have developed an ¹⁸F-labeled ligand for non-invasive...

BACKGROUND Gliomas are highly invasive and infiltrative solid tumors that present significant clinical challenges in terms of achieving complete surgical resection. These tumors often harbor mutated isocitrate dehydrogenase enzymes (mIDH), making them attractive theranostic targets. Therefore, accurately assessing mIDH status is essential for effec...

The understanding of the contribution of the tumour microenvironment to cancer progression and metastasis, in particular the interplay between tumour cells, fibroblasts and the extracellular matrix has grown tremendously over the last years. Lysyl oxidases are increasingly recognised as key players in this context, in addition to their function as...

Cancer patients are at a very high risk of serious thrombotic events, often fatal. The causes discussed include the detachment of thrombogenic particles from tumor cells or the adverse effects of chemotherapeutic agents. Cytostatic agents can either act directly on their targets or, in the case of a prodrug approach, require metabolization for thei...

The development of novel ligands for G-protein-coupled receptors (GPCRs) typically entails the characterization of their binding affinity, which is often performed with radioligands in a competition or saturation binding assay format. Since GPCRs are transmembrane proteins, receptor samples for binding assays are prepared from tissue sections, cell...

Targeting inflammatory mediators and related signaling pathways may offer a rational strategy for the treatment of cancer. The incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes in dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids is a promising...

Prostate specific membrane antigen (PSMA) is an excellent target for imaging and treatment of prostate carcinoma (PCa). Unfortunately, not all PCa cells express PSMA. Therefore, alternative theranostic targets are required. The membrane protein prostate stem cell antigen (PSCA) is highly overexpressed in most primary prostate carcinoma (PCa) cells...

Amyotrophic lateral sclerosis (ALS) is a devastating motoneuron disease characterized by sustained loss of neuromuscular junctions, degenerating corticospinal motoneurons and rapidly progressing muscle paralysis. Motoneurons have unique features, essentially a highly polarized, lengthy architecture of axons, posing a considerable challenge for main...

The presence of inflammatory mediators in the tumor microenvironment, such as cytokines, growth factors or eicosanoids, indicate cancer‐related inflammatory processes. Targeting these inflammatory mediators and related signal pathways may offer a rational strategy for the treatment of cancer. This study focuses on the incorporation of metabolically...

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the most widely used therapeutics against pain, fever, and inflammation; additionally, antitumor properties are reported. NSAIDs reduce the synthesis of prostaglandins by inhibiting the cyclooxygenase (COX) isoforms COX‐1 and COX‐2. As nonselective inhibition is associated with off‐target effects, s...

Glioblastoma (GBM) is still an incurable tumor that is associated with high recurrence rate and poor survival despite the current treatment regimes. With the urgent need for novel therapeutic strategies, immunotherapies, especially chimeric antigen receptor (CAR)-expressing T cells, represent a promising approach for specific and effective targetin...

Context: Pheochromocytomas/paragangliomas (PPGLs) with pathogenic mutations in the succinate dehydrogenase subunit B (SDHB) are associated with a high metastatic risk. Somatostatin receptor 2 (SSTR2)-dependent imaging is the most sensitive imaging modality for SDHB-related PPGLs, suggesting that SSTR2 expression is a significant cell surface thera...

Functional interaction between cancer cells and the surrounding microenvironment is still not sufficiently understood, which motivates the tremendous interest for the development of numerous in vitro tumor models. Diverse parameters, e.g., transport of nutrients and metabolites, availability of space in the confinement, etc. make an impact on the s...

The potential of designing irreversible alkyne-based inhibitors of cysteine cathepsins by isoelectronic replacement in reversibly acting potent peptide nitriles was explored. The synthesis of the dipeptide alkynes was developed with special emphasis on stereochemically homogeneous products obtained in the Gilbert-Seyferth homologation for C≡C bond...

The Front Cover shows fish representing fenoprofen analogues. In contrast to the phenyl analogue (left pufferfish), the carborane derivative (right inflated carboranefish) is more cytotoxic. Fenoprofen is a widely used nonsteroidal anti‐inflammatory drug (NSAID) against rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis, and g...

Extracellular matrix (ECM) provides various types of direct interactions with cells and a dynamic environment, which can be remodeled through different assembly/degradation mechanisms to adapt to different biological processes. Herein, through introducing polyphosphate-modified hyaluronic acid and bioactive glass (BG) nano-fibril into a self-assemb...

Detection of antigens and antibodies (Abs) is of great importance in determining the infection and immunity status of the population, as they are key parameters guiding the handling of pandemics. Current point-of-care (POC) devices are a convenient option for rapid screening; however, their sensitivity requires further improvement. We present an in...

Although chronic inflammation inhibits bone healing, the healing process is initiated by an inflammatory phase. In a well-tuned sequence of molecular events, pro-inflammatory cytokines are secreted to orchestrate the inflammation response to injury and the recruitment of progenitor cells. These events in turn activate the secretion of anti-inflamma...

Multi-target drugs (MTDs) are emerging alternatives to combination therapies. Since both histone deacetylases (HDACs) and cyclooxygenase-2 (COX-2) are known to be overexpressed in several cancer types, we herein report the design, synthesis, and biological evaluation of a library of dual HDAC-COX inhibitors. The designed compounds were synthesized...

Fenoprofen is a widely used nonsteroidal anti‐inflammatory drug (NSAID) against rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and gout. Like other NSAIDs, fenoprofen inhibits the synthesis of prostaglandins by blocking both cyclooxygenase (COX) isoforms, COX‐1 the “house‐keeping” enzyme and COX‐2 the induced isoform from...

The endothelium plays a key role in the dynamic balance of hemodynamic, humoral and inflammatory processes in the human body. Its central importance and the resulting therapeutic concepts are the subject of ongoing research efforts and form the basis for the treatment of numerous diseases. The pulmonary endothelium is an essential component for the...

In addition to the classic functions of proteins, such as acting as a biocatalyst or binding partner, the conformational states of proteins and their remodeling upon stimulation need to be considered. A prominent example of a protein that undergoes comprehensive conformational remodeling is transglutaminase 2 (TGase 2), the distinct conformational...

The selective inhibition of enzymes that catalyze the conversion of arachidonic acid to inflammatory eicosanoids represents a promising approach for cancer therapy. This study, therefore, focuses on the incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes into existing dual cycloxygenase‐2 (COX‐2)/5‐lipoxygenase (...

The applicability of radioligands for targeted endoradionuclide therapy is limited due to radiation-induced toxicity to healthy tissues, in particular to the kidneys as primary organs of elimination. The targeting of enzymes of the renal brush border membrane by cleavable linkers that permit the formation of fast eliminating radionuclide-carrying c...

Pheochromocytomas and paragangliomas (PCCs/PGLs) are catecholamine-producing tumors. In inoperable and metastatic cases, somatostatin type 2 receptor (SSTR2) expression allows for peptide receptor radionuclide therapy with [¹⁷⁷Lu]Lu-DOTA-TATE. Insufficient receptor levels, however, limit treatment efficacy. This study evaluates whether the epigenet...

Bone in diabetes mellitus is characterized by an altered microarchitecture caused by abnormal metabolism of bone cells. Together with diabetic neuropathy, this is associated with serious complications including impaired bone healing culminating in complicated fractures and dislocations, especially in the lower extremities, so-called Charcot neuroar...

We report a nonadentate bispidine (3,7-diazabicyclo[3.3.1]nonane) that unveils the potential to bind theranostically relevant radionuclides, including indium-111, lutetium-177, and actinium-225 under mild labeling conditions. This radiopharmaceutical candidate allows the simultaneous application of imaging and treatment (radionuclide theranostics)...

Overexpression of the neurotensin receptor type 1 (NTS1R), a peptide receptor located at the plasma membrane, has been reported for a variety of malignant tumors. Thus, targeting the NTS1R with 18F- or 68Ga-labeled ligands is considered a straightforward approach towards in vivo imaging of NTS1R-expressing tumors via positron emission tomography (P...

Increased dietary phosphate intake has been associated with severity of coronary artery disease, increased carotid intima–media thickness, left ventricular hypertrophy (LVH), and increased cardiovascular mortality and morbidity in individuals with normal renal function as well as in patients suffering from chronic kidney disease. However, the under...

COX-2 can be considered as a clinically relevant molecular target for adjuvant, in particular radiosensitizing treatments. In this regard, using selective COX-2 inhibitors, e.g., in combination with radiotherapy or endoradiotherapy, represents an interesting treatment option. Based on our own findings that nitric oxide (NO)-releasing and celecoxib-...

Pheochromocytomas (PCCs) are rare but potentially lethal tumors that arise from the adrenal medulla. The clinical suspicion and diagnosis of PCC can be challenging due to the non-specific nature of signs and symptoms. In many patients, infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could lead to long-term symptoms inclu...

The characterization of novel radiotracers toward their metabolic stability is an essential part of their development. While in vitro methods such as liver microsome assays or ex vivo blood or tissue samples provide information on overall stability, little or no information is obtained on cytochrome P450 (CYP) enzyme and isoform-specific contributi...

Functional interaction between cancer cells and the surrounding microenvironment is still not sufficiently understood, which motivates the tremendous interest for the development of numerous in vitro and in vivo tumor models. Diverse parameters, e.g., transport of nutrients and metabolites, availability of space in the confinement, interaction with...

Mefenamic acid represents a widely used nonsteroidal anti-inflammatory drug (NSAID) to treat the pain of postoperative surgery and heavy menstrual bleeding. Like other NSAIDs, mefenamic acid inhibits the synthesis of prostaglandins by nonselectively blocking cyclooxygenase (COX) isoforms COX-1 and COX-2. For the improved selectivity of the drug and...

Ligands combining a bis(phosphonate) group with a macrocycle function as metal isotope carriers for radionuclide-based imaging and for treating bone metastases associated with several cancers. However, bis(phosphonate) pendant arms often...

Transglutaminase 2 (TGase 2) is a multifunctional protein which is involved in various physiological and pathophysiological processes. The latter also include its participation in the development and progression of malignant neoplasms, which are often accompanied by increased protein synthesis. In addition to the elucidation of the molecular functi...

Transglutaminase 2 (TG2) is a protein expressed in many tissues that exerts numerous, sometimes contradictory, intra- and extracellular functions, under both physiological and pathophysiological conditions. In the context of tumor progression, it has been found to be involved in cell adhesion, DNA repair mechanisms, induction of apoptosis, and mese...

Recent oncological studies identified beneficial properties of radiation applied at ultrahigh dose rates, several orders of magnitude higher than the clinical standard of the order of Gy min –1 . Sources capable of providing these ultrahigh dose rates are under investigation. Here we show that a stable, compact laser-driven proton source with energ...

Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular targeting is being increasingly considered, but with variable results. This study investigates established and novel molecular-targeted drugs and chemotherapeutic agents for the treatment of PPGLs in human primary cultures and murine cell line spheroids. I...

The inducible isoenzyme cyclooxygenase-2 (COX-2) is an important hub in cellular signaling, which contributes to tumor progression by modulating and enhancing a pro-inflammatory tumor microenvironment, tumor growth, apoptosis resistance, angiogenesis and metastasis. In order to understand the role of COX-2 expression in melanoma, we investigated th...

Stem cell bioengineering and therapy require different model systems and materials in different stages of development. If a chemically defined biomatrix system can fulfill most tasks, it can minimize the discrepancy among various setups. By screening biomaterials synthesized through a coacervation‐mediated self‐assembling mechanism, a biomatrix sys...

Malignant melanoma has a steadily increasing incidence, but treatment options are still limited and prognosis for patients, especially for men, is poor. To investigate whether targeting estrogen receptor (ER) signaling is a valid therapeutic approach, we retrospectively analyzed ER gene expression profiles in 448 melanoma patients. High ERα gene ex...

The intentional binding of radioligands to albumin gains increasing attention in the context of radiopharmaceutical cancer therapy as it can lead to an enhanced radioactivity uptake into the tumor lesions and, thus, to a potentially improved therapeutic outcome. However, the influence of the radioligand’s albumin-binding affinity on the time profil...