Enhancing capacity and synthesis of [68Ga]68-Ga-PSMA-HBED-CC with the lyophilized ready-to-use kit for nuclear pharmacy applications.

INTRODUCTION: The authors describe the newly proposed synthesis technique for the gallium-68 (Ga-68)-labeled tracer ([Ga]Ga-PSMA-HBED-CC) for imaging expression of the prostate-specific membrane antigen (PSMA). An effort was applied to design the lyophilized cold kit (isoPROtrace-11) as a time-saving technique resulting in increased radiochemical yields. PROCEDURES: The initial material for labeling was obtained from a Ge/Ga-generator. For labeling with the lyophilized cold kit isoPROtrace-11, 2.5 ml 0.1 M HCl of the middle Ga-68 elution fraction were added to the kit, shook for dissolving the vial's contents and kept for 5 minutes at room temperature. A systematic comparison was carried out between results obtained with the cold kit technique and with previously used Modular-Lab module concerning the radiochemical yield, purity, and the time of producing. RESULTS: Automated module-involved synthesis of [Ga]Ga-PSMA-HBED- CC resulted in a radiochemical yield of 84.2 ± 6.3% and purity of >95% after 25 minutes. The room temperature cold kit gave a radiochemical yield of >98% and purity of >95% after 5 minutes. CONCLUSION: Using the kit method reduced the labeling time. The cold kit method increased production efficiency because less of the eluted Ga-68 was wasted.

Regulation of the neuronal KCNQ2 channel by Src--a dual rearrangement of the cytosolic termini underlies bidirectional regulation of gating.

Neuronal M-type K(+) channels are heteromers of KCNQ2 and KCNQ3 subunits, and are found in cell bodies, dendrites and the axon initial segment, regulating the firing properties of neurons. By contrast, presynaptic KCNQ2 homomeric channels directly regulate neurotransmitter release. Previously, we have described a mechanism for gating downregulation of KCNQ2 homomeric channels by calmodulin and syntaxin1A. Here, we describe a new mechanism for regulation of KCNQ2 channel gating that is modulated by Src, a non-receptor tyrosine kinase. In this mechanism, two concurrent distinct structural rearrangements of the cytosolic termini induce two opposing effects: upregulation of the single-channel open probability, mediated by an N-terminal tyrosine, and reduction in functional channels, mediated by a C-terminal tyrosine. In contrast, Src-mediated regulation of KCNQ3 homomeric channels, shown previously to be achieved through the corresponding tyrosine residues, involves the N-terminal-tyrosine-mediated downregulation of the open probability, rather than an upregulation. We argue that the dual bidirectional regulation of KCNQ2 functionality by Src, mediated through two separate sites, means that KCNQ2 can be modified by cellular factors that might specifically interact with either one of the sites, with potential significance in the fine-tuning of neurotransmitters release at nerve terminals.