Synthesis, Radiolabeling, and Preliminary in vivo Evaluation of [68Ga] IPCAT-NOTA as an Imaging Agent for Dopamine Transporter.

INTRODUCTION: Novel radiotracer development for imaging dopamine transporters is a subject of interest because although [99mTc]TRODAT-1, [123I]ß-CIT, and [123I]FP-CIT are commercially available; 99Mo/99mTc generator is in short supply and 123I production is highly dependent on compact cyclotron. Therefore, we designed a novel positron emission tomography (PET) tracer based on a tropane derivative through C-2 modification to conjugate NOTA for chelating 68Ga, a radioisotope derived from a 68Ge/68Ga generator. METHODS: IPCAT-NOTA 22 was synthesized and labeled with [68Ga]GaCl4 - at room temperature. Biological studies on serum stability, LogP, and in vitro autoradiography (binding assay and competitive assay) were performed. Furthermore, ex vivo autoradiography, biodistribution, and dynamic PET imaging studies were performed in Sprague Dawley rats. RESULTS: [68Ga]IPCAT-NOTA 24 obtained had a radiochemical yield of ≥90% and a specific activity of 4.25 MBq/nmol. [68Ga]IPCAT-NOTA 24 of 85% radiochemical purity (RCP%) was stable at 37°C for up to 60 minutes in serum with a lipophilicity of 0.88. The specific binding ratio (SBR%) reached 15.8 ± 6.7 at 60 minutes, and the 85% specific uptake could be blocked through co-injection at 100- and 1000-fold of the cold precursor in in vitro binding studies. Tissue regional distribution studies in rats with [68Ga]IPCAT-NOTA 24 showed striatal uptake (0.02% at 5 minutes and 0.007% at 60 minutes) with SBR% of 6%, 25%, and 62% at 5-15, 30-40, and 60-70 minutes, respectively, in NanoPET studies. The RCP% of [68Ga]IPCAT-NOTA 24 at 30 minutes in vivo remained 67.65%. CONCLUSION: Data described here provide new information on the design of PET probe of conjugate/pendent approach for DAT imaging. Another chelator or another direct method of intracranial injection must be used to prove the relation between [68Ga]IPCAT-NOTA 24 uptake and transporter localization.

Structural and nanomechanical properties of BiFeO3 thin films deposited by radio frequency magnetron sputtering.

The nanomechanical properties of BiFeO3 (BFO) thin films are subjected to nanoindentation evaluation. BFO thin films are grown on the Pt/Ti/SiO2/Si substrates by using radio frequency magnetron sputtering with various deposition temperatures. The structure was analyzed by X-ray diffraction, and the results confirmed the presence of BFO phases. Atomic force microscopy revealed that the average film surface roughness increased with increasing of the deposition temperature. A Berkovich nanoindenter operated with the continuous contact stiffness measurement option indicated that the hardness decreases from 10.6 to 6.8 GPa for films deposited at 350°C and 450°C, respectively. In contrast, Young's modulus for the former is 170.8 GPa as compared to a value of 131.4 GPa for the latter. The relationship between the hardness and film grain size appears to follow closely with the Hall-Petch equation.

Dislocation Energetics and Pop-Ins in AlN Thin Films by Berkovich Nanoindentation.

Nanoindentation-induced multiple pop-ins were observed in the load-displacement curves when the mechanical responses of AlN films grown on c-plane sapphire substrates were investigated by using Berkovich indenters. No evidence of phase transformation is revealed by cross-sectional transmission electron microscopy (XTEM) and selected area diffraction (SAD) analyses. Instead XTEM observations suggest that these "instabilities" resulted from the sudden nucleation of dislocations propagating along the slip systems lying on the {0001} basal planes and the pyramidal planes commonly observed in hexagonal compound semiconductors. Based on this scenario, an energetic estimation of dislocation nucleation is made.

Recent advances in imaging of dopaminergic neurons for evaluation of neuropsychiatric disorders.

Dopamine is the most intensely studied monoaminergic neurotransmitter. Dopaminergic neurotransmission plays an important role in regulating several aspects of basic brain function, including motor, behavior, motivation, and working memory. To date, there are numerous positron emission tomography (PET) and single photon emission computed tomography (SPECT) radiotracers available for targeting different steps in the process of dopaminergic neurotransmission, which permits us to quantify dopaminergic activity in the living human brain. Degeneration of the nigrostriatal dopamine system causes Parkinson's disease (PD) and related Parkinsonism. Dopamine is the neurotransmitter that has been classically associated with the reinforcing effects of drug abuse. Abnormalities within the dopamine system in the brain are involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Dopamine receptors play an important role in schizophrenia and the effect of neuroleptics is through blockage of dopamine D(2) receptors. This review will concentrate on the radiotracers that have been developed for imaging dopaminergic neurons, describe the clinical aspects in the assessment of neuropsychiatric disorders, and suggest future directions in the diagnosis and management of such disorders.

The role of molecular imaging in the diagnosis and management of neuropsychiatric disorders.

Neuropsychiatric disorders are becoming a major socioeconomic burden to modern society. In recent years, a dramatic expansion of tools has facilitated the study of the molecular basis of neuropsychiatric disorders. Molecular imaging has enabled the noninvasive characterization and quantification of biological processes at the cellular, tissue, and organism levels in intact living subjects. This technology has revolutionized the practice of medicine and has become critical to quality health care. New advances in research on molecular imaging hold promise for personalized medicine in neuropsychiatric disorders, with adjusted therapeutic doses, predictable responses, reduced adverse drug reactions, early diagnosis, and personal health planning. In this paper, we discuss the development of radiotracers for imaging dopaminergic, serotonergic, and noradrenergic systems and ß-amyloid plaques. We will underline the role of molecular imaging technologies in various neuropsychiatric disorders, describe their unique strengths and limitations, and suggest future directions in the diagnosis and management of neuropsychiatric disorders.