Clemens Decristoforo

Clemens Decristoforo
Medizinische Universität Innsbruck · Department of Nuclear Medicine

Prof.

About

452
Publications
64,508
Reads
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8,977
Citations
Additional affiliations
February 2010 - present
Medizinische Universität Innsbruck
Position
  • Radiopharmaceutical Scientist
August 2009 - February 2010
International Atomic Energy Agency (IAEA)
Position
  • Radiopharmaceutical Scientist
October 2005 - present
FH Gesundheit
Position
  • Lecturer
Description
  • Radiopharmacy for Radiology Technologists
Education
October 1991 - April 1997
University of Innsbruck
Field of study
  • Radiopharmacy
October 1983 - February 1991
University of Innsbruck
Field of study
  • Pharmacy

Publications

Publications (452)
Article
Full-text available
This review covers publications on siderophores applied for molecular imaging applications, mainly for radionuclide-based imaging. Siderophores are low molecular weight chelators produced by bacteria and fungi to scavenge essential iron. Research on these molecules has a continuing history over the past 50 years. Many biomedical applications have b...
Article
Positron emission tomography (PET) as well as optical imaging (OI) with peptide receptor targeting probes have proven their value for oncological applications but also show restrictions depending on the clinical field of interest. Therefore the combination of both methods, particularly in a single molecule, could improve versatility in clinical rou...
Article
Full-text available
The 30th Annual Congress of the European Association of Nuclear Medicine (EANM) was held in Vienna, Austria, from 21 to 25 October 2017 under the chairmanship of Professor Francesco Giammarile. As always, the Congress was a great success: more than 6,379 participants came from 90 countries from all continents. Participants were presented with an ex...
Article
Full-text available
The inverse electron-demand Diels-Alder reaction between 1,2,4,5-tetrazine (Tz) and trans-cyclooct-2-ene (TCO) has gained increasing attraction among extensive studies on click chemistry due to its exceptionally fast reaction kinetics and high selectivity for in vivo pretargeting applications including PET imaging. The facile two-step approach util...
Article
Full-text available
Purpose Aspergillus fumigatus produces the siderophore triacetylfusarinine C (TAFC) for iron acquisition which is essential for its virulence. Therefore, TAFC is a specific marker for invasive aspergillosis. We have shown previously that positron emission tomography (PET) imaging with [⁶⁸Ga]TAFC exhibited excellent targeting properties in an A. fum...
Article
Aspergillus fumigatus is responsible for thousands of cases of invasive fungal disease annually. For iron uptake, A. fumigatus secretes so-called siderophores, which are taken up after the binding of environmental iron.
Article
Full-text available
This document is intended as a supplement to the EANM “Guidelines on current Good Radiopharmacy Practice (cGRPP)” issued by the Radiopharmacy Committee of the EANM (Gillings et al. in EJNMMI Radiopharm Chem. 6:8, 2021). The aim of the EANM Radiopharmacy Committee is to provide a document that describes how to manage risks associated with small-scal...
Article
Full-text available
Background The development of radiopharmaceuticals requires extensive evaluation before they can be applied in a diagnostic or therapeutic setting in Nuclear Medicine. Chemical, radiochemical, and pharmaceutical parameters must be established and verified to ensure the quality of these novel products. Main body To provide supportive evidence for t...
Preprint
Coronavirus disease 2019 (COVID-19)-related pneumonia challenges clinical practice. We explore the potential diagnostic benefit of positron emission tomography/computed tomography (PET/CT) in order to establish the underlying inflammatory or fibrotic repair processes in prolonged structural lung abnormalities in COVID-19 patients. Methods: Six post...
Article
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The EANM herewith clearly expresses its commitment and support to the non-commercial in-house preparation of radiopharmaceuticals for direct use in accordance with European and national regulations.
Article
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As multidrug-resistant bacteria are an emerging problem and threat to humanity, novel strategies for treatment and diagnostics are actively sought. We aim to utilize siderophores, iron-specific strong chelating agents produced by microbes, as gallium ion carriers for diagnosis, applying that Fe(III) can be successfully replaced by Ga(III) without l...
Article
Full-text available
Fungal infections are a serious threat, especially for immunocompromised patients. Early and reliable diagnosis is crucial to treat such infections. The bacterially produced siderophore desferrioxamine B (DFO-B) is utilized by a variety of microorganisms for iron acquisition, while mammalian cells lack the uptake of DFO-B chelates. DFO-B is clinica...
Article
Invasive pulmonary aspergillosis (IPA) is a severe life-threatening condition. Diagnosis of fungal disease in general, and especially that caused by Aspergillus fumigatus is problematic. A. fumigatus secretes siderophores to acquire iron during infection, which are also essential for virulence. We describe the chemoacetylation of ferrated fusarinin...
Article
Full-text available
Invasive pulmonary aspergillosis (IPA) is a life-threatening form of fungal infection, primarily in immunocompromised patients and associated with significant mortality. Diagnostic procedures are often invasive and/or time consuming and existing antifungals can be constrained by dose-limiting toxicity and drug interaction. In this study, we modifie...
Article
Full-text available
Background: 68Ga-PSMA-11 PET/CT is a promising method for the assessment of local recurrence (LR) in prostate cancer (PCa) patients. The aim of this study was to evaluate the diagnostic performance of early 68Ga-PSMA-11 PET imaging in comparison to 68Ga-PSMA-11 PET imaging 60 min post-injection (p.i.) in the detection of LR in patients with bioche...
Article
Full-text available
The new minigastrin analog DOTA-MGS5 is a promising new candidate for targeting cholecystokinin-2 receptor (CCK2R)-expressing tumors. To enable the clinical translation of PET/CT imaging using 68 Ga-labeled DOTA-MGS5, different quality and safety aspects need to be considered to comply with the regulatory framework for clinical trial application. T...
Article
Full-text available
Recent years have seen the establishment of several radionuclides as medicinal products in particular in the setting of theranostics and PET. [177Lu]Lutetium Chloride or [64Cu]Copper Chloride have received marketing authorization as radionuclide precursor, [68Ga]Gallium Chloride has received regulatory approval in the form of different 68Ge/68Ga ge...
Preprint
Full-text available
Invasive pulmonary aspergillosis (IPA) is a life-threatening form of fungal infection, primarily in immunocompromised patients and associated with a significant mortality. Diagnostic procedures are often invasive and/or time consuming and existing antifungals can be constrained by dose limiting toxicity and drug interaction. In this study, we modif...
Article
Full-text available
Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Results This commentary of highlights has resulted in 23 different topics selected by each member of the Editorial Board addressing a variety of aspects ra...
Article
Purpose: The aim of this study was to assess a) the impact of forced diuresis with early furosemide injection on the detection rate of local recurrence (LR) in prostate cancer (PC) patients with biochemical recurrence (BR) referred for 68Ga-labelled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (68Ga-PSMA-11) Positron Emission Tomography/Computed Tomography (PET/C...
Article
Full-text available
This guideline on current good radiopharmacy practice (cGRPP) for small-scale preparation of radiopharmaceuticals represents the view of the Radiopharmacy Committee of the European Association of Nuclear Medicine (EANM). The guideline is laid out in the format of the EU Good Manufacturing Practice (GMP) guidelines as defined in EudraLex volume 4. I...
Article
Full-text available
Purpose: With the increase of especially hospital-acquired infections, timely and accurate diagnosis of bacterial infections is crucial for effective patient care. Molecular imaging has the potential for specific and sensitive detection of infections. Siderophores are iron-specific chelators recognized by specific bacterial transporters, represent...
Chapter
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Due to the complex nomenclature used in various regulations and guidance documents, the understanding of radiopharmaceutical precursor's definition might be challenging. Depending on the context it could be interpreted as the substance which becomes a radiopharmaceutical after radiolabeling with a radionuclide of choice or a radionuclide which is u...
Article
Full-text available
Background The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to describe trends in the field. Results This commentary of highlights has resulted in 19 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man app...
Article
Full-text available
Purpose: to assess the influence of intravenous hydration and forced diuresis with furosemide in two different dosages (20 vs 40 mg) on the intensity of tracer accumulation in the urinary collection system and on the occurrence of halo artefact surrounding the urinary bladder and kidneys in [68Ga]Ga-PSMA-11-PET/CT scans. Materials and methods: C...
Chapter
Radiopharmaceuticals have to be extensively tested in their development before they can be applied on humans. Whereas radiolabeling tests and analytical testing are an essential part to ensure the quality of the radiopharmaceutical, the efficacy in terms of diagnostic performance or therapeutic action as well as the safety of is of paramount import...
Chapter
Legislation of Radiopharmaceuticals is concerned with their radioactive nature and the related safety standards in handling them, but also, based on their definition as medicinal products in most countries worldwide both for diagnostic and therapeutic applications, with pharmaceutical regulations. This chapter covers the pharmaceutical regulations...
Article
Full-text available
Recently, radiolabelled antagonists targeting somatostatin receptors subtype 2 (SST2) in neuroendocrine neoplasms demonstrated certain superior properties over agonists. Within the ERA-PerMED project “TECANT” two 99mTc-Tetramine (N4)-derivatized SST2 antagonists (TECANT-1 and TECANT-2) were studied for the selection of the best candidate for clinic...
Article
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Antifungal resistance of human fungal pathogens represents an increasing challenge in modern medicine. Short antimicrobial peptides (AMP) display a promising class of antifungals with a different mode of action, but lack target specificity and metabolic stability. In this study the hexapeptide PAF26 (Ac-dArg-dLys-dLys-dTrp-dPhe-dTrp-NH2) and the th...
Article
Introduction The information on the presence of cold metal complexes in radiolabeled DOTA-TATE or DOTA-TOC is important in assessing the cause of the radiolabeling failure, poor radiolabeling yield and/or low effective molar activity. DOTA-peptide complexes are detectable using UV-Vis detector. The main limitation in the quantitative analysis is th...
Article
Full-text available
Live-cell imaging allows the in vivo analysis of subcellular localisation dynamics of physiological processes with high spatial-temporal resolution. However, only few fluorescent dyes have been custom-designed to facilitate species-specific live-cell imaging approaches in filamentous fungi to date. Therefore, we developed fluorescent dye conjugates...
Article
Full-text available
Invasive fungal infections such as aspergillosis are life-threatening diseases mainly affecting immuno-compromised patients. The diagnosis of fungal infections is difficult, lacking specificity and sensitivity. This review covers findings on the preclinical use of siderophores for the molecular imaging of infections. Siderophores are low molecular...
Article
Full-text available
Hybrid imaging combining the beneficial properties of radioactivity and optical imaging within one imaging probe has gained increasing interest in radiopharmaceutical research. In this study, we modified the macrocyclic gallium-68 chelator fusarinine C (FSC) by conjugating a fluorescent moiety and tetrazine (Tz) moieties. The resulting hybrid imagi...
Article
Full-text available
Background & Aims Ferroportin disease (FD) and hemochromatosis type 4 (HH4) are associated with variants in the ferroportin encoding gene SLC40A1 . Both phenotypes are characterized by iron overload despite being caused by distinct variants that either mediate reduced cellular iron export in FD or resistance against hepcidin‐induced inactivation of...
Article
Introduction: Gastrin Releasing peptide receptors (GRPRs) are potential molecular imaging targets in a variety of tumors. Recently, a 68Ga-labelled antagonist to GRPRs, NeoBOMB1, was developed for PET. We report on the outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38) within the EU-FP7 project Closed-loop Molecular Environment for Mi...
Article
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Background: To fulfil good manufacturing requirements, analytical methods for the analysis of pharmaceuticals for human and vetinary use must be validated. The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has published guidance documents on the requirements for such val...
Article
Full-text available
Aspergillus fumigatus (A. fumigatus) is a human pathogen causing severe invasive fungal infections, lacking sensitive and selective diagnostic tools. A. fumigatus secretes the siderophore desferri-triacetylfusarinine C (TAFC) to acquire iron from the human host. TAFC can be labelled with gallium-68 to perform positron emission tomography (PET/CT) s...
Article
Cyclic pentapeptides containing the amino acid sequence arginine-glycine-aspartic (RGD) have been widely applied to target αvβ3 integrin, which is upregulated in various tumors during tumor-induced angiogenesis. Multimeric cyclic RGD peptides have been reported to be advantageous over monomeric counterparts for angiogenesis imaging. Here, we prepar...
Article
The development of so-called Proticles opens attractive possibilities for new drug delivery systems. Proticles are nanoparticles (NPs), which are formed by self-assembly of negatively charged oligonucleotides in combination with the positively charged peptide protamine. Polyethylene glycol (PEG) is a widely known pharmaceutical agent to stop partic...
Article
Full-text available
The EU directive 2001/83 describes the community code for medicinal products for human use including radiopharmaceuticals. In its current definition, also radionuclide precursors, such as fluorine-18, need to hold a marketing authorization before being placed on the market. The potential of novel radiopharmaceuticals for nuclear medicine is, althou...
Article
Full-text available
VL-2397 (previously termed ASP2397) is an antifungal, aluminum-chelating cyclic hexapeptide with a structure analogous to ferrichrome-type siderophores, whereby replacement of aluminum by iron was shown to decrease the antifungal activity of this compound. Here we found that inactivation of an importer for ferrichrome-type siderophores, termed Sit1...
Chapter
The development of radiopharmaceuticals is essential for nuclear medicine, implementing new findings in molecular biology, drug development, and in many fields of clinical specialities, increasing its pace in particular in the field of PET and therapeutic applications. New radionuclides are emerging; an increased need of radiopharmaceuticals as com...
Article
Full-text available
Abstract New regulatory guidance documents from the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have recently been finalized or are in draft format outlining new pathways for preclinical safety testing. The US and the European Union appear to be moving in a similar direction focussing and refining precli...
Article
Full-text available
Fusarinine C (FSC) has recently been shown to be a promising and novel chelator for 89Zr. Here, FSC has been further derivatized to optimize the complexation properties of FSC-based chelators for 89Zr-labeling by introducing additional carboxylic groups. These were expected to improve the stability of 89Zr-complexes by saturating the 8-coordination...
Article
Full-text available
With the development of ever more radiopharmaceuticals suitable for theranostic applications, translation of novel compounds from the preclinical stage towards clinical application becomes a bottleneck for the advances in Nuclear Medicine. This review article summarizes the current regulatory framework for clinical trials with radiopharmaceuticals...
Article
Full-text available
The high overexpression of cholecystokinin-2 receptors (CCK2R) in tumors, such as medullary thyroid carcinoma, allows for highly specific diagnostic and therapeutic targeting with radiolabeled peptide probes derived from natural ligands for the receptor. Based on the ideal imaging characteristics, high availability and low cost of technetium-99m (9...
Article
Molecular imaging and targeted radiotherapy with radiolabeled cholecystokinin-2 receptor (CCK2R) targeting peptide probes holds high promise to improve the clinical management of patients with metastatic medullary thyroid carcinoma and other CCK2R-expressing malignancies. Low stability and suboptimal targeting of currently available radiolabeled pe...
Article
Full-text available
Pseudomonas aeruginosa is an increasingly prevalent opportunistic pathogen that causes a variety of life-threatening nosocomial infections. Novel strategies for the development of new antibacterial treatments as well as diagnostic tools are needed. One of the novel diagnostic strategies for the detection of infection could be the utilization of sid...
Article
Full-text available
Aim: The purpose of this study was to investigate the diagnostic performance of 68Ga-PSMA-11 PET/CT in the evaluation of bone metastases in metastatic prostate cancer (PC) patients scheduled for radionuclide therapy in comparison to [18F]sodium fluoride (18F-NaF) PET/CT. Methods: Sixteen metastatic PC patients with known skeletal metastases, who...
Article
In recent years, several new radiotracers and radionuclide therapies have been developed. There is a renaissance in nuclear medicine and molecular imaging today, for example, in terms of the ability to image and treat neuroendocrine and prostate malignancies. In order to be able to bring a new drug product from bench to bedside and assist patients,...