TY  - JOUR
A1  - Jarick, I.
A1  - Volckmar, A. L.
A1  - Pütter, C.
A1  - Pechlivanis, S.
A1  - Nguyen, T. T.
A1  - Dauvermann, M. R.
A1  - Beck, S.
A1  - Albayrak, Ö.
A1  - Scherag, S.
A1  - Gilsbach, S.
A1  - Cichon, S.
A1  - Hoffmann, P.
A1  - Degenhardt, F.
A1  - Nöthen, M. M.
A1  - Schreiber, S.
A1  - Wichmann, H. E.
A1  - Jöckel, K. H.
A1  - Heinrich, J.
A1  - Tiesler, C. M. T.
A1  - Faraone, S. V.
A1  - Walitza, S.
A1  - Sinzig, J.
A1  - Freitag, C.
A1  - Meyer, J.
A1  - Herpertz-Dahlmann, B.
A1  - Lehmkuhl, G.
A1  - Renner, T. J.
A1  - Warnke, A.
A1  - Romanos, M.
A1  - Lesch, K. P.
A1  - Reif, A.
A1  - Schimmelmann, B. G.
A1  - Hebebrand, J.
A1  - Scherag, A.
A1  - Hinney, A.
T1  - Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder
JF  - Molecular Psychiatry
N2  - Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls \((P=2.8 × 10^{-4})\) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients \((P=1.2 × 10^{-3})\) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control \((P=4.3 × 10^{-2})\). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.
KW  - children
KW  - ADHD
KW  - CNVs
KW  - GWAS
KW  - PARK2
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121131
VL  - 19
IS  - 19
ER  - 
TY  - JOUR
A1  - Jain, M.
A1  - Vélez, J. I.
A1  - Acosta, M. T.
A1  - Palacio, L. G.
A1  - Balog, J.
A1  - Roessler, E.
A1  - Pineda, D.
A1  - Londoño, A. C.
A1  - Palacio, J. D.
A1  - Arbelaez, A.
A1  - Lopera, F.
A1  - Elia, J.
A1  - Hakonarson, H.
A1  - Seitz, C.
A1  - Freitag, C. M.
A1  - Palmason, H.
A1  - Meyer, J.
A1  - Romanos, M.
A1  - Walitza, S.
A1  - Hemminger, U.
A1  - Warnke, A.
A1  - Romanos, J.
A1  - Renner, T.
A1  - Jacob, C.
A1  - Lesch, K.-P.
A1  - Swanson, J.
A1  - Castellanos, F. X.
A1  - Bailey-Wilson, J. E.
A1  - Arcos-Burgos, M.
A1  - Muenke, M.
T1  - A cooperative interaction between LPHN3 and 11q doubles the risk for ADHD
JF  - Molecular Psychiatry
N2  - In previous studies of a genetic isolate, we identified significant linkage of attention deficit hyperactivity disorder (ADHD) to 4q, 5q, 8q, 11q and 17p. The existence of unique large size families linked to multiple regions, and the fact that these families came from an isolated population, we hypothesized that two-locus interaction contributions to ADHD were plausible. Several analytical models converged to show significant interaction between 4q and 11q (P<1 × 10−8) and 11q and 17p (P<1 × 10−6). As we have identified that common variants of the LPHN3 gene were responsible for the 4q linkage signal, we focused on 4q–11q interaction to determine that single-nucleotide polymorphisms (SNPs) harbored in the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 genes, to double the risk of developing ADHD. This interaction not only explains genetic effects much better than taking each of these loci effects by separated but also differences in brain metabolism as depicted by proton magnetic resonance spectroscopy data and pharmacogenetic response to stimulant medication. These findings not only add information about how high order genetic interactions might be implicated in conferring susceptibility to develop ADHD but also show that future studies of the effects of genetic interactions on ADHD clinical information will help to shape predictive models of individual outcome.
KW  - ADHD
KW  - genetic interaction
KW  - LPHN3
KW  - NCAM1
KW  - DRD2
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125128
VL  - 17
ER  - 
TY  - JOUR
A1  - Serfling, S.
A1  - Zhi, Y.
A1  - Schirbel, A.
A1  - Lindner, T.
A1  - Meyer, T.
A1  - Gerhard-Hartmann, E.
A1  - Lappa, C.
A1  - Hagen, R.
A1  - Hackenberg, S.
A1  - Buck, A. K.
A1  - Scherzad, A.
T1  - Improved cancer detection in Waldeyer’s tonsillar ring by \(^{68}\)Ga-FAPI PET/CT imaging
JF  - European Journal of Nuclear Medicine and Molecular Imaging
N2  - Purpose
In cancer of unknown primary (CUP), positron emission tomography/computed tomography (PET/CT) with the glucose analog [\(^{18}\)F]FDG represents the standard imaging approach for localization of the malignant primary. Frequently, however, [\(^{18}\)F]FDG PET/CT cannot precisely distinguish between small occult tumors and chronic inflammation, especially in Waldeyer’s tonsillar ring. To improve the accuracy for detecting primary tumors in the Waldeyer’s tonsillar ring, the novel PET tracer [\(^{68}\)Ga]Ga-FAPI-4 for specific imaging of fibroblast activation protein (FAP) expression was used as a more specific target for cancer imaging.

Methods
Eight patients with suspicion of a malignant tumor in Waldeyer’s tonsillar ring or a CUP syndrome were examined. PET/CT scans with [\(^{18}\)F]-FDG and [\(^{68}\)Ga]Ga-FAPI-4 were performed for pre-operative tumor localization. After surgical resection, histopathological and immunohistochemical results were compared to PET/CT findings.

Results
Histopathology revealed a palatine or lingual tonsil carcinoma in all patients. In case of lymph node metastases smaller than 7 mm in size, the [\(^{18}\)F]FDG PET/CT detection rate of cervical lymph node metastases was higher than that of [\(^{68}\)Ga]FAPI PET/CT, while both tracers identified the primary tumors in all eight cases. The size of the primary and the lymph node metastases was directly correlated to the respective FAP expression, as detected by immunohistochemistry. The mean SUVmax for the primary tumors was 21.29 ± 7.97 for \(^{18}\)F-FDG and 16.06 ± 6.29 for \(^{68}\)Ga-FAPI, respectively (p = 0.2). The mean SUVmax for the healthy contralateral tonsils was 8.38 ± 2.45 for [\(^{18}\)F]FDG and 3.55 ± 0.47 for [\(^{68}\)Ga]FAPI (p < 0.001). The SUVmax ratio of [68Ga]FAPI was significantly different from [\(^{18}\)F] FDG (p = 0.03). Mean TBRmax for the [\(^{68}\)Ga]Ga-FAPI-4 tracer was markedly higher in comparison to [\(^{18}\)F]FDG (10.90 vs. 4.11).

Conclusion
Non-invasive imaging of FAP expression by [\(^{68}\)Ga]FAPI PET/CT resulted in a better visual detection of the malignant primary in CUP, as compared to [\(^{18}\)F]FDG imaging. However, the detection rate of lymph node metastases was inferior, presumably due to low FAP expression in small metastases. Nevertheless, by offering a detection method for primary tumors with the potential of lower false positive rates and thus avoiding biopsies, patients with CUP syndrome may benefit from [\(^{68}\)Ga]FAPI PET/CT imaging.
KW  - Waldeyer’s tonsillar ring
KW  - cancer of unknown primary (CUP)
KW  - positron emission tomography/computed tomography
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235271
SN  - 1619-7070
VL  - 48
ER  - 
TY  - JOUR
A1  - Grimm, Martin
A1  - Gasser, Martin
A1  - Bueter, Marco
A1  - Strehl, Johanna
A1  - Wang, Johann
A1  - Nichiporuk, Ekaterina
A1  - Meyer, Detlef
A1  - Germer, Christoph T.
A1  - Waaga-Gasser, Ana M.
A1  - Thalheimer, Andreas
T1  - Evaluation of immunological escape mechanisms in a mouse model of colorectal liver metastases
N2  - Background: The local and systemic activation and regulation of the immune system by malignant cells during carcinogenesis is highly complex with involvement of the innate and acquired immune system. Despite the fact that malignant cells do have antigenic properties their immunogenic effects are minor suggesting tumor induced mechanisms to circumvent cancer immunosurveillance. The aim of this study is the analysis of tumor immune escape mechanisms in a colorectal liver metastases mouse model at different points in time during tumor growth. Methods: CT26.WT murine colon carcinoma cells were injected intraportally in Balb/c mice after median laparotomy using a standardized injection technique. Metastatic tumor growth in the liver was examined by standard histological procedures at defined points in time during metastatic growth. Liver tissue with metastases was additionally analyzed for cytokines, T cell markers and Fas/Fas-L expression using immunohistochemistry, immunofluorescence and RT-PCR. Comparisons were performed by analysis of variance or paired and unpaired t test when appropriate. Results: Intraportal injection of colon carcinoma cells resulted in a gradual and time dependent metastatic growth. T cells of regulatory phenotype (CD4+CD25+Foxp3+) which might play a role in protumoral immune response were found to infiltrate peritumoral tissue increasingly during carcinogenesis. Expression of cytokines IL-10, TGF-b and TNF-a were increased during tumor growth whereas IFN-g showed a decrease of the expression from day 10 on following an initial increase. Moreover, liver metastases of murine colon carcinoma show an up-regulation of FAS-L on tumor cell surface with a decreased expression of FAS from day 10 on. CD8+ T cells express FAS and show an increased rate of apoptosis at perimetastatic location. Conclusions: This study describes cellular and macromolecular changes contributing to immunological escape mechanisms during metastatic growth in a colorectal liver metastases mouse model simulating the situation in human cancer.
KW  - Krebs <Medizin>
KW  - colon carcinoma cells
KW  - carcinogenesis
KW  - human cancer
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67899
ER  - 
TY  - JOUR
A1  - Schartl, Manfred
A1  - Schlupp, Ingo
A1  - Schartl, Angelika
A1  - Meyer, Manfred K.
A1  - Nanda, Indrajit
A1  - Schmid, Michael
A1  - Epplen, Jörg T.
A1  - Parzefall, Jakob
T1  - On the stability of dispensable constituents of the eukaryotic genome: Stability of coding sequences versus truly hypervariable sequences in a clonal vertebrate, the amazon molly, Poecilia formosa
N2  - In dooal unisexual vertebrales, the genes specifying the males become dispensable. To study tbe rate of such geoes the gynogeoetic all-female fisb Poecilillfonnolll was treated with androgens. Phenotypic males were obtained that exbibited the complete set of male cbaracteristics of dosely related gooocboristic species, induding body proportions, pigmentation, the extremely complex insemination apparatus of poecilüd fish, sexual bebavior, and spermatogeoesls. Tbe apparent stabllity of such genic structures, induding those involved in androgen regulation, is contrasted by high instability of noncoding sequeaces. Frequent mutations, thelr donal transmission, and at least two truly hypervariable Iod leading to individual difl'ereaces between these othenrise donal organisms were detected by DNA fingerprinting. These observations substantiate the concept that also in "ameiotic" vertebrates certain compartments of the genome are more prooe to mutatiooal alterations than others.
KW  - Physiologische Chemie
KW  - DNA fingerprinting
KW  - androgen-induced masculinization
KW  - gynogeaesls
KW  - simple repeat sequences
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61731
ER  - 
TY  - JOUR
A1  - Dupuis, Luc
A1  - Dengler, Reinhard
A1  - Heneka, Michael T.
A1  - Meyer, Thomas
A1  - Zierz, Stephan
A1  - Kassubek, Jan
A1  - Fischer, Wilhelm
A1  - Steiner, Franziska
A1  - Lindauer, Eva
A1  - Otto, Markus
A1  - Dreyhaupt, Jens
A1  - Grehl, Torsten
A1  - Hermann, Andreas
A1  - Winkler, Andrea S.
A1  - Bogdahn, Ulrich
A1  - Benecke, Reiner
A1  - Schrank, Bertold
A1  - Wessig, Carsten
A1  - Grosskreutz, Julian
A1  - Ludolph, Albert C.
T1  - A Randomized, Double Blind, Placebo-Controlled Trial of Pioglitazone in Combination with Riluzole in Amyotrophic Lateral Sclerosis
JF  - PLoS One
N2  - Background: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS). 
Methods/Principal Findings: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. 
Conclusion/Significance: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole.
KW  - ALS
KW  - transgenic mouse model
KW  - central nervous system
KW  - nonalcoholic steatohepatitis
KW  - PPAR-gamme
KW  - hexanucleotide repeat
KW  - disease progression
KW  - delays progression
KW  - SOD1 mutations
KW  - monocycline
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130255
VL  - 7
IS  - 6
ER  - 
TY  - JOUR
A1  - Winter, Patrick
A1  - Kampf, Thomas
A1  - Helluy, Xavier
A1  - Gutjahr, Fabian T.
A1  - Meyer, Cord B.
A1  - Rommel, Eberhard
A1  - Bauer, Wolfgang R.
A1  - Jakob, Peter M.
A1  - Herold, Volker
T1  - Fast retrospectively triggered local pulse-wave velocity measurements in mice with CMR-microscopy using a radial trajectory
JF  - Journal of Cardiovascular Magnetic Resonance
N2  - Background

The aortic pulse-wave velocity (PWV) is an important indicator of cardiovascular risk. In recent studies MRI methods have been developed to measure this parameter noninvasively in mice. Present techniques require additional hardware for cardiac and respiratory gating. In this work a robust self-gated measurement of the local PWV in mice without the need of triggering probes is proposed.

Methods

The local PWV of 6-months-old wild-type C57BL/6J mice (n=6) was measured in the abdominal aorta with a retrospectively triggered radial Phase Contrast (PC) MR sequence using the flow-area (QA) method. A navigator signal was extracted from the CMR data of highly asymmetric radial projections with short repetition time (TR=3 ms) and post-processed with high-pass and low-pass filters for retrospective cardiac and respiratory gating. The self-gating signal was used for a reconstruction of high-resolution Cine frames of the aortic motion. To assess the local PWV the volume flow Q and the cross-sectional area A of the aorta were determined. The results were compared with the values measured with a triggered Cartesian and an undersampled triggered radial PC-Cine sequence.

Results

In all examined animals a self-gating signal could be extracted and used for retrospective breath-gating and PC-Cine reconstruction. With the non-triggered measurement PWV values of 2.3±0.2 m/s were determined. These values are in agreement with those measured with the triggered Cartesian (2.4±0.2 m/s) and the triggered radial (2.3±0.2 m/s) measurement. Due to the strong robustness of the radial trajectory against undersampling an acceleration of more than two relative to the prospectively triggered Cartesian sampling could be achieved with the retrospective method.

Conclusion

With the radial flow-encoding sequence the extraction of a self-gating signal is feasible. The retrospective method enables a robust and fast measurement of the local PWV without the need of additional trigger hardware.
KW  - pulse-wave velocity
KW  - mouse
KW  - self-gating
KW  - phase-contrast CMR
KW  - non-triggered
KW  - retrospective
KW  - radial
KW  - aorta
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96602
UR  - http://jcmr-online.com/content/15/1/88
ER  - 
TY  - CHAP
A1  - Epplen, J. T.
A1  - Ammer, H.
A1  - Epplen, C.
A1  - Kammerbauer, C.
A1  - Mitreiter, R.
A1  - Roewer, L.
A1  - Schwaiger, W.
A1  - Steimle, V.
A1  - Zischler, H.
A1  - Albert, E.
A1  - Andreas, A.
A1  - Beyermann, B.
A1  - Meyer, W.
A1  - Buitkamp, J.
A1  - Nanda, I.
A1  - Nürnberg, P.
A1  - Pena, S. D. J.
A1  - Pöche, H.
A1  - Sprecher, W.
A1  - Schartl, Manfred
A1  - Weising, K.
A1  - Yassouridis, A.
T1  - Oligonucleotide fingerprinting using simple repeat motifs: a convenient, ubiquitously applicable method to detect hypervariability for multiple purposes
N2  - A panel of simple repetitive oligonucleotide probes has been designed and tested for multilocus DNA fingerprinting in some 200 fungal, plant and animal species as well as man. To date at least one of the probes has been found to be informative in each species. The human genome, however, has been the major target of many fingerprintins studies. Using the probe (CAC)5 or (GTG)5, individualization of all humans is possible except for monozygotic twins. Paternity analyses are now perfonned on a routine basis by the use of multilocus fingerprints, inctuding also cases of deficiency, i.e. where one of the parents is not available for analysis. In forensie science stain analysis is feasible in all tissue remains containing nuc)eated cells. Depending on the degree of DNA degradation a variety of oligonucleotides are informative, and they have been proven useful in actual case work. Advantages in comparison to other methods including enzymatic DNA amplification techniques (PCR) are evident. Fingerprint patterns of tumors may be changed due to the gain or loss of chromosomes and/or intrachromosomal deletion and amplification events. Locus-specific probes were isolated from the human (CAC)5/( GTG)5 fingerprint with a varying degree of informativeness (monomorphic versus truly hypervariable markers). The feasibility of three different approaches. for the isolation of hypervariable mono-locus probes was evaluated. Finally, one particular mixed simple (gt)n(ga)m repeat locus in the second intron of the HLA-DRB genes has been scrutinized to allow comparison of the extent of exon-encoded (protein-) polymorphisms versus intronie bypervariability of simple repeats: adjacent to a single gene sequence (e.g. HLA-DRB1*0401) many different length alleles were found. Group-specific structures of basic repeats were identified within the evolutionarily related DRB alleles. As a further application it is suggested here that due to the ubiquitous interspersion of their targets, short probes for simple repeat sequences are especially useful tools for ordering genomic cosmid, yeast artificial chromosome and phage banks.
KW  - DNS
KW  - Fingerprint-Verfahren
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86371
ER  - 
TY  - JOUR
A1  - Brumberg, Joachim
A1  - Schröter, Nils
A1  - Blazhenets, Ganna
A1  - Frings, Lars
A1  - Volkmann, Jens
A1  - Lapa, Constantin
A1  - Jost, Wolfgang H.
A1  - Isaias, Ioannis U.
A1  - Meyer, Philipp T.
T1  - Differential diagnosis of parkinsonism: a head-to-head comparison of FDG PET and MIBG scintigraphy
JF  - NPJ Parkinsons Disease
N2  - [\(^{18}\)F]fluorodeoxyglucose (FDG) PET and [\(^{123}\)I]metaiodobenzylguanidine (MIBG) scintigraphy may contribute to the differential diagnosis of neurodegenerative parkinsonism. To identify the superior method, we retrospectively evaluated 54 patients with suspected neurodegenerative parkinsonism, who were referred for FDG PET and MIBG scintigraphy. Two investigators visually assessed FDG PET scans using an ordinal 6-step score for disease-specific patterns of Lewy body diseases (LBD) or atypical parkinsonism (APS) and assigned the latter to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal syndrome. Regions-of-interest analysis on anterior planar MIBG images served to calculate the heart-to-mediastinum ratio. Movement disorder specialists blinded to imaging results established clinical follow-up diagnosis by means of guideline-derived case vignettes. Clinical follow-up (1.7 +/- 2.3 years) revealed the following diagnoses: n = 19 LBD (n = 17 Parkinson's disease [PD], n = 1 PD dementia, and n = 1 dementia with Lewy bodies), n = 31 APS (n = 28 MSA, n = 3 PSP), n = 3 non-neurodegenerative parkinsonism; n = 1 patient could not be diagnosed and was excluded. Receiver operating characteristic analyses for discriminating LBD vs. non-LBD revealed a larger area under the curve for FDG PET than for MIBG scintigraphy at statistical trend level for consensus rating (0.82 vs. 0.69, p = 0.06; significant for investigator #1: 0.83 vs. 0.69, p = 0.04). The analysis of PD vs. MSA showed a similar difference (0.82 vs. 0.69, p = 0.11; rater #1: 0.83 vs. 0.69, p = 0.07). Albeit the notable differences in diagnostic performance did not attain statistical significance, the authors consider this finding clinically relevant and suggest that FDG PET, which also allows for subgrouping of APS, should be preferred.
KW  - clinical diagnosis
KW  - F-18-FDG PET
KW  - disease
KW  - dementia
KW  - accuracy
KW  - stimulation
KW  - guidelines
KW  - criteria
KW  - brain
KW  - risk
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230675
VL  - 6
ER  - 
TY  - JOUR
A1  - Hartrampf, Philipp E.
A1  - Lapa, Constantin
A1  - Serfling, Sebastian E.
A1  - Buck, Andreas K.
A1  - Seitz, Anna Katharina
A1  - Meyer, Philipp T.
A1  - Ruf, Juri
A1  - Michalski, Kerstin
T1  - Development of Discordant Hypermetabolic Prostate Cancer Lesions in the Course of [\(^{177}\)Lu]PSMA Radioligand Therapy and Their Possible Influence on Patient Outcome
JF  - Cancers
N2  - Simple Summary
Discordant FDG-positive but PSMA-negative (FDG+/PSMA−) metastases constitute a negative prognostic marker of overall survival in patients undergoing PSMA radioligand therapy (RLT). The aim of this analysis was to investigate the prognostic implications of new FDG+/PSMA− lesions, which occur during or after PSMA RLT. In a retrospective bicentric analysis of 32 patients undergoing PSMA RLT and follow-up dual tracer staging with PSMA and FDG PET/CT, FDG+/PSMA− lesions occurred in a limited number of patients. However, the presence of FDG+/PSMA− lesions appears not to have a significant impact on the OS, but further studies are needed to establish the clinical relevance of such lesions.

Abstract
Introduction: Positron emission tomography/computer tomography (PET/CT) targeting the prostate-specific membrane antigen (PSMA) is crucial for the assessment of adequate PSMA expression in patients with metastatic castration-resistant prostate cancer (mCRPC) prior to PSMA radioligand therapy (PSMA RLT). Moreover, initial dual tracer staging using combined PSMA and [\(^{18}\)F]fluorodeoxyglucose (FDG) PET/CT provides relevant information, since discordant FDG-positive but PSMA-negative (FDG+/PSMA−) lesions constitute a negative prognostic marker of overall survival (OS) after PSMA RLT. However, little is known about the prognostic implications of dual tracer imaging for restaging at follow-up. The aim of this analysis was to investigate the prognostic implications of new FDG+/PSMA− lesions during or after PSMA RLT. Methods: This bicentric analysis included 32 patients with mCRPC who underwent both FDG and PSMA PET/CT imaging after two or four cycles of PSMA RLT. Patients with FDG+/PSMA− lesions prior to PSMA RLT were not considered. The presence of FDG+/PSMA− lesions was assessed with follow-up dual tracer imaging of patients after two or four cycles of PSMA RLT. Patients with at least one new FDG+/PSMA− lesion were compared to patients without any FDG+/PSMA− lesions at the respective time points. A log-rank analysis was used to assess the difference in OS between subgroups. Results: After two cycles of PSMA RLT, four of 32 patients (13%) had FDG+/PSMA− metastases. No significant difference in OS was observed (p = 0.807), as compared to patients without FDG+/PSMA− lesions. Follow-up dual tracer imaging after the 4th cycle of PSMA RLT was available in 18 patients. Of these, four patients presented with FDG+/PSMA− findings (n = 2 already after two cycles). After the fourth cycle of PSMA RLT, no significant difference in OS was observed between patients with and without FDG+/PSMA− lesions (p = 0.442). Conclusion: This study shows that FDG+/PSMA− lesions develop in a limited number of patients undergoing PSMA RLT. Further studies are needed to establish the clinical relevance of such lesions.
KW  - PSMA
KW  - FDG
KW  - PET/CT
KW  - prostate cancer
KW  - radioligand therapy
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245168
SN  - 2072-6694
VL  - 13
IS  - 17
ER  - 
TY  - JOUR
A1  - Brumberg, Joachim
A1  - Blazhenets, Ganna
A1  - Schröter, Nils
A1  - Frings, Lars
A1  - Jost, Wolfgang H.
A1  - Lapa, Constantin
A1  - Meyer, Philipp T.
T1  - Imaging cardiac sympathetic innervation with MIBG: linear conversion of the heart-to-mediastinum ratio between different collimators
JF  - EJNMMI Physics
N2  - Background
The heart-to-mediastinum (H/M) ratio is a commonly used parameter to measure cardiac I-123 metaiodobenzylguanidine (MIBG) uptake. Since the H/M ratio is substantially influenced by the collimator type, we investigated whether an empirical linear conversion of H/M ratios between camera systems with low-energy (LE) and medium-energy (ME) collimator is possible.

Methods
We included 18 patients with parkinsonism who were referred to one of the two participating molecular imaging facilities for the evaluation of cardiac sympathetic innervation by MIBG scintigraphy. Two consecutive planar image datasets were acquired with LE and ME collimators at 4 h after MIBG administration. Linear regression analyses were performed to describe the association between the H/M ratios gained with both collimator settings, and the accuracy of a linear transfer of the H/M ratio between collimators and across centers was assessed using a leave-one-out procedure.

Results
H/M ratios acquired with LE and ME collimators showed a strong linear relationship both within each imaging facility (R\(^2\) = 0.99, p < 0.001 and R\(^2\) = 0.90, p < 0.001) and across centers (H/M-LE = 0.41 × H/M-ME + 0.63, R\(^2\) = 0.97, p < 0.001). A linear conversion of H/M ratios between collimators and across centers was estimated to be very accurate (mean absolute error 0.05 ± 0.04; mean relative absolute error 3.2 ± 2.6%).

Conclusions
The present study demonstrates that a simple linear conversion of H/M ratios acquired with different collimators is possible with high accuracy. This should greatly facilitate the exchange of normative data between settings and pooling of data from different institutions.
KW  - MIBG
KW  - collimator
KW  - heart-to-mediastinum ratio
KW  - linear conversion
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221675
VL  - 6
ER  -