Peter Brust

Publications (136) View all

• Article: [German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids].

  K-J Langen, P Bartenstein, H Boecker, P Brust, H H Coenen, A Drzezga, F Grünwald, B J Krause, T Kuwert, O Sabri, K Tatsch, W A Weber, M Schreckenberger
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  ABSTRACT: For the primary diagnosis of brain tumours, morphological imaging by means of magnetic resonance imaging (MRI) is the current method of choice. The complementary use of functional imaging by positron emitting tomography (PET) and single photon emitting computerized tomography (SPECT) with labelled amino acids can provide significant information on some clinically relevant questions, which are beyond the capacity of MRI. These diagnostic issues affect in particular the improvement of biopsy targeting and tumour delineation for surgery and radiotherapy planning. In addition, amino acid labelled PET and SPECT tracers are helpful for the differentiation between tumour recurrence and non-specific post-therapeutic tissue changes, in predicting prognosis of low grade gliomas, and for metabolic monitoring of treatment response. The application of dynamic PET examination protocols for the assessment of amino acid kinetics has been shown to enable an improved non-invasive tumour grading. The purpose of this guideline is to provide practical assistance for indication, examination procedure and image analysis of brain PET/SPECT with labelled amino acids in order to allow for a high quality standard of the method. After a short introduction on pathobiochemistry and radiopharmacy of amino acid labelled tracers, concrete and detailed information is given on the several indications, patient preparation and examination protocols as well as on data reconstruction, visual and quantitative image analysis and interpretation. In addition, possible pitfalls are described, and the relevant original publications are listed for further information.
  Nuklearmedizin 01/2011; 50(4):167-73. · 1.28 Impact Factor
• Article: Carbon-11 labeled indolylpropylamine analog as a new potential PET agent for imaging of the serotonin transporter.

  R Ben-Daniel, W Deuther-Conrad, M Scheunemann, J Steinbach, P Brust, E Mishani
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  ABSTRACT: The synthesis and structure-activity relationship of a new class of indole derivatives with low-nanomolar affinity for the SERT and high selectivity versus the 5-HT1A receptor were recently reported. Based on their chemical structure, four new indolylpropylamine derivatives which contain atoms to afford future labeling with PET isotopes, were synthesized and evaluated as SERT ligands. The chemistry of these novel derivatives, their biological evaluation, the general method of preparing the precursor indole for labeling, and the C-11 labeling of the most promising indole derivative, are described herein.
  Bioorganic & medicinal chemistry 07/2008; 16(12):6364-70. · 2.82 Impact Factor
• Article: Norchloro-fluoro-homoepibatidine (NCFHEB) - a promising radioligand for neuroimaging nicotinic acetylcholine receptors with PET.

  W Deuther-Conrad, J T Patt, P R Lockman, D D Allen, M Patt, A Schildan, V Ganapathy, J Steinbach, O Sabri, P Brust
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  ABSTRACT: Cholinergic neurotransmission depends on the integrity of nicotinic acetylcholine receptors (nAChRs), and impairment of both is characteristic for various neurodegenerative diseases. Visualization of specific receptor subtypes by positron emission tomography (PET) has potential to assist with diagnosis of such neurodegenerative diseases and with design of suitable therapeutic approaches. The goal of our study was to evaluate in vivo the potential of (18)F-labelled (+)- and (-)-norchloro-fluoro-homoepibatidine ([(18)F]NCFHEB) in comparison to 2-[(18)F]F-A-85380 as PET tracers. In the brains of NMRI mice, highest levels of radioactivity were detected at 20 min post-injection of (+)-[(18)F]NCFHEB, (-)-[(18)F]NCFHEB, and 2-F-[(18)F]-A-85380 (7.45, 5.60, and 3.2% ID/g tissue, respectively). No marked pharmacological adverse effects were observed at 25 mug NCFHEB/kg. Uptake studies in RBE4 cells and in situ perfusion studies suggest an interaction of epibatidine and NCFHEB with the carrier-mediated choline transport at the blood-brain barrier. The data indicate that (+)- and (-)-[(18)F]NCFHEB have potential for further development as PET tracers.
  European Neuropsychopharmacology 04/2008; 18(3):222-9. · 4.05 Impact Factor
• Article: In vivo measurement of the serotonin transporter with (S)-([18F]fluoromethyl)-(+)-McN5652.

  P Brust, R Hinz, H Kuwabara, S Hesse, J Zessin, B Pawelke, H Stephan, R Bergmann, J Steinbach, O Sabri
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  ABSTRACT: The radiolabeled serotonin transporter (SERT) ligand [(11)C](+)-McN5652 has recently been used in clinical positron emission tomography (PET) studies for SERT imaging. However, this radioligand offers disadvantages in routine clinical settings because of its short radioisotope half-life (eg PET facilities within hospitals without a cyclotron need to acquire such radioligands from distant cyclotron units for clinical use). S-([(18)F]fluoromethyl)-(+)-McN5652 ([(18)F](+)-FMe-McN5652) is an analogue which has been synthesized newly, and has a significantly longer radioisotope half-life. In the porcine brain, it demonstrates the same characteristic distribution pattern of serotonin-uptake sites like the (11)C-labeled congener with the highest binding in the midbrain and thalamus and the lowest in the cerebellum and occipital cortex. It shows a 30% higher blood-brain transfer and a slower peripheral metabolism than [(11)C](+)-McN5652. Rather uniform brain binding was observed after injection of the pharmacologically inactive radiolabeled enantiomer, or after pretreatment with the highly selective SERT inhibitor citalopram. The norepinephrine uptake inhibitor maprotiline did not show any inhibitory effect. Using a one-tissue compartment model (K(1), k"(2)) or a two-tissue compartment model (K(1) to k(4)) with or without constraints for calculation, the regional binding parameters of [(11)C](+)-McN5652 and [(18)F](+)-FMe-McN5652 are highly correlated among each other and with the SERT density, as determined by in vitro binding of [(3)H]citalopram. Using constraints to correct for the free fraction and nonspecific binding of the radiotracers, a considerable increase of the midbrain-occipital cortex ratios with higher values for [(18)F](+)-FMe-McN5652 compared to [(11)C](+)McN5652 was revealed. It is concluded that [(18)F](+)-FMe-McN5652 has better features than [(11)C](+)McN5652 for SERT imaging with PET.
  Neuropsychopharmacology 12/2003; 28(11):2010-9. · 7.99 Impact Factor
• Article: Distribution of 16alpha-[18F]fluoro-estradiol-3,17beta-disulfamate in rats, tumour-bearing mice and piglets.

  P Brust, H Rodig, J Römer, H Kasch, R Bergmann, F Füchtner, D Zips, M Baumann, J Steinbach, B Johannsen
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  ABSTRACT: Based on a high affinity to the enzyme estrone sulfatase (ES), 16alpha-[18F]fluoroestradiol-3,17beta-disulfamate ([18F]FESDS) has been suggested as a potential PET radiotracer for imaging steroid-dependent breast tumours. The distribution of [18F]FESDS was studied in rats, tumour-bearing nude mice and piglets. In all species evidence for binding to a second target, the enzyme carbonic anhydrase (CA), was obtained. ES and CA inhibitors significantly reduced the radiotracer uptake in various organs but not in tumours. It is concluded that [18F]FESDS binds to ES and CA in vivo but this binding is not strong enough to allow tumour imaging with positron emission tomography (PET).
  Applied Radiation and Isotopes 12/2002; 57(5):687-95. · 1.17 Impact Factor