ABSTRACT
68Ga-radiolabeled small molecules that specifically target prostate-specific membrane antigen (PSMA) have been extensively investigated, and some of these tracers have been used in the diagnosis of prostate cancer via 68Ga-positron emission tomography (68Ga-PET). Nevertheless, current 68Ga-labeled radiotracers show only fair detection rates for metastatic prostate cancer lesions, especially those with lower levels of prostate specific antigen (PSA), which often occurs in the biochemical recurrence of prostate cancer. The goal of this study was to design and synthesize a new PSMA-targeted radiotracer, 68Ga-SC691, with high affinity for prostate cancer cells and excellent pharmacokinetics. To this end, structural optimization was carried out on the bifunctional group, target motif, and linker while the high affinity targeting scaffold remained. To explore its potential in the clinic, a comparative study was further performed in vitro and in vivo between 68Ga-SC691 and 68Ga-PSMA-11, a clinically approved tracer for PSMA-positive prostate cancer. SC691 was radiolabeled to provide 68Ga-SC691 in 99% radiolabeling yield under mild conditions. High uptake and a high internalization ratio into LNCaP cells were observed in in vitro studies. In vivo studies showed that 68Ga-SC691 had favorable biodistribution properties and could specifically accumulate on PSMA-positive LNCaP xenografts visualized by micro-PET/CT. This radiotracer showed excellent PET imaging quality and comparable, if not higher, uptake in LNCaP xenografts than 68Ga-PSMA-11.
Subject(s)
Glutamate Carboxypeptidase II/antagonists & inhibitors , Prostate/diagnostic imaging , Prostatic Neoplasms/diagnosis , Radiopharmaceuticals/pharmacokinetics , Animals , Antigens, Surface/metabolism , Cell Line, Tumor , Gallium Isotopes/administration & dosage , Gallium Isotopes/pharmacokinetics , Gallium Radioisotopes/administration & dosage , Gallium Radioisotopes/pharmacokinetics , Glutamate Carboxypeptidase II/metabolism , Humans , Male , Mice , Positron Emission Tomography Computed Tomography/methods , Prostate/pathology , Prostatic Neoplasms/pathology , Radiopharmaceuticals/administration & dosage , Tissue Distribution , X-Ray Microtomography/methods , Xenograft Model Antitumor AssaysABSTRACT
Third harmonic generation by a weak femtosecond probe pulse intersecting a pump laser-induced plasma in air is investigated and a general model is developed to describe such signal, applicable to a wide range of focusing and plasma conditions. The effect of the surrounding air on the generated signal is discussed. The third-order nonlinear susceptibility of an air plasma with electron density N(e) is determined to be χ(p)((3)) = χ(a)((3)) + γ(p)N(e) with γ(p) = 2 ± 1 × 10(-49) m(5) V(-2) and χ(a)((3)) being the third-order susceptibility in air. Lateral scans of the probe through the plasma are used to determine electron density profiles and the effect of focusing and phase mismatch is discussed.
ABSTRACT
The transient electron temperature in a weakly ionized femtosecond-laser-produced air plasma filament was determined from optical absorption and diffraction experiments. The electron temperature and plasma density decay on similar time scales of a few hundred picoseconds. Comparison with plasma theory reveals the importance of inelastic collisions that lead to energy transfer to vibrational degrees of freedom of air molecules during the plasma cooling.
ABSTRACT
A surface plasmon resonance (SPR) sensing technique based on polarization interferometry and angle modulation is presented. Its sensitivity is not a direct function of variation of reflection intensity, nor of phase shift. Rather, it is a function of the complex reflection coefficient. A three times standard deviation detection limit of 5.1 x 10(-7) refractive index units in a 2 Hz bandwidth is obtained with our experimental setup. A theoretical analysis shows that this technique can provide a wide linear measurement range. Moreover, the sensitivity is insensitive to the thickness of gold films over approximately 5 nm. This SPR sensing technique is suitable for physical, chemical, and biological research.
