Browsing by Author "Kramer, Vasko"

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    Imaging Nigrostriatal Dopaminergic Deficit in Holmes Tremor with 18F-PR04.MZ-PET/CT
    (2015) Juri Clavería, Carlos Andrés; Chana, Pedro; Kramer, Vasko; Pruzzo, Rossana; Amaral, Horacio; Riss, Patrick J.; Rösch, Frank
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    Pharmacokinetic evaluation of [18F]PR04.MZ for PET/CT imaging and quantification of dopamine transporters in the human brain
    (2020) Kramer, Vasko; Juri, Carlos; Riss, Patrick J.; Pruzzo, Rossana; Soza-Ried, Cristian; Flores, Jonathan; Hurtado, Ana; Roesch, Frank; Chana-Cuevas, Pedro; Amaral, Horacio
    Purpose Dopamine transporters (DAT) modulate pre-synaptic dopamine and physiological functions such as movement and reward. DAT also mirrors disease state in neurological disorders, rendering it an essential diagnostic target. [F-18]PR04.MZ is a new PET imaging agent for DAT with an improved affinity and selectivity profile, for which we here describe the complete pharmacokinetic evaluation in healthy controls. Methods Thirty-two healthy subjects underwent T1-weighted MRI and dynamic PET scans for 180 min with arterial blood sampling (n = 5) or 90 min without blood sampling (n = 25) after injection of 197.6 +/- 12.2 MBq [F-18]PR04.MZ. Blood and plasma metabolite analysis were performed. MRI-based normalization of brain images, delineation of VOIs, and kinetic modeling was conducted to determine distribution volumes (V-t) and binding potentials (BPnd). The impact of scan duration was evaluated and repeated PET scans were performed to assess test-retest variability (n = 5). A static imaging protocol has been validated for clinical applications. Results [F-18]PR04.MZ showed rapid metabolization in circulation, very high uptake in striatum and midbrain, and very low non-specific binding. The two-tissue compartment model 2TCM provided best fits for measured time-activity-curves and calculated V(t)s in putamen, caudate, substantia nigra pars compacta (SNpc), and cerebellar cortex were 11.83, 9.73, 2.12, and 0.57, respectively. All non-invasive models correlated well with BPnd values derived from 2TCM but underestimated DAT availability by about 28-33%. Of those, simplified reference tissue model (SRTM) provided the best fits, lowest Akaike Information Criteria values, and BPnd values of 14.82, 11.95, and 2.63 in putamen, caudate, and SNpc, respectively. BPnd estimates for striatal regions and SNpc were stable between 90 and 130 min post-injection. Test-retest results were excellent, showing low variability in all and excellent reliability in most relevant regions. Static imaging from 60 to 90-min post-injection is a viable alternative for quantification. Conclusions [F-18]PR04.MZ is a PET tracer with very high affinity, selectivity, and specific uptake in striatum and midbrain. 2TCM and SRTM provide good fits, high and stable V(t)s or BP(nd)s, and good test-retest reliability for precise quantification of DAT in human subjects.
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    Prodromal manifestations of Parkinson’s disease in adults with 22q11.2 microdeletion syndrome
    (2022) Juri, Carlos; Chaná-Cuevas, Pedro; Kramer, Vasko; Fritsch, Rosemarie; Ornstein, Claudia; Cuiza, Analía; Hernández, Carlos; Villanueva, Katiuska; Cordova, Teresa; Mauro, Jorge; Ocampo, Adrián; Rebolledo-Jaramillo, Boris; Repetto, Gabriela M.
    22q11.2 microdeletion syndrome (22qDS) was recently identified as a risk factor for development of early-onset Parkinson´s disease (PD). The classical motor manifestations of this disease are preceded by early signs and symptoms of neurodegeneration. The progression of 22qDS-associated PD is unknown. We aimed to evaluate the presence of prodromal PD in a group of adults with 22qDS using the Movement Disorders Society (MDS) Criteria for Prodromal PD. Thirty-eight persons with 22qDS and 13 age-matched controls participated in the study, and their results were compared using the MannWhitney U test. Persons with 22qDS had lower scores on olfaction testing (p=7.42Ex10-5), higher scores on the COMPASS 31 scale for dysautonomia (p=2.28x10-3) and on the motor evaluation using Movement Disorder Society (MDS)-sponsored revision of Unified Parkinson’s Disease Rating Scale motor subscore (UPDRS-III) (p=1.84x10-4), compared with healthy controls. Home polysomnogram did not find participants with REM-sleep behavior disorder. Integrity of nigrostriatal dopaminergic system was evaluated by PET-CT imaging of presynaptic dopamine with 18F-PR04.MZ. Patients showed significantly higher specific binding ratios in the striatum, compared to controls (p=9.57x10-3 at the caudate nuclei). Two patients with 22qDS (5.2%) had decreased uptake in the posterior putamen (less than 60% of controls) and one fulfilled MDS criteria for prodromal PD. These results show that patients with 22qDS manifest some signs and symptoms of prodromal PD such as hyposmia, dysautonomia and mild movement alterations. In the majority, this was associated with elevated dopaminergic signaling, suggesting that loss of dopaminergic neurons may not be the cause. A smaller subgroup did show evidence of a decrease in nigrostriatal dopaminergic signaling, as seen in classical prodromal PD. Longitudinal studies are necessary to understand the progression to and risk of PD in persons with 22qDS.
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    [18F]PR04.MZ PET/CT Imaging for Evaluation of Nigrostriatal Neuron Integrity in Patients With Parkinson Disease
    (2021) Juri, Carlos; Kramer, Vasko; Riss, Patrick J.; Soza-Ried, Cristian; Haeger, Arlette; Pruzzo, Rossana; Rosch, Frank; Amaral, Horacio; Chana-Cuevas, Pedro
    Introduction