Treatment in a Human Lymphoma Xenograft Model

Researchers from Millennium Pharmaceuticals have demonstrated significant accuracy and dynamic sensitivity of Cerenkov Luminescence Imaging (CLI) against conventional PET imaging techniques. CLI is an emerging imaging modality similar to bio-luminescence imaging which is being investigated as a more rapid, lower-cost alternative to PET for preclinical drug discovery applications. CLI captures visible protons emitted byCerenkov Radiation, the phenomenon responsible for the bluish glow often seen in nuclear reactors and the inspiration forDr. Manhattan’s Blueish Appearance.

The research, which was published in The Journal of Nuclear Medicine, demonstrated a very high correlation between CLI and PET imaging analyses of radio-pharmaceutical (F-FDG) uptake in an in vivo preclinical anti-tumor study. dr-manhattan

Cerenkov luminescence imaging (CLI) is an emerging imaging technique that combines aspects of both optical and nuclear imaging fields. The ability to fully evaluate the correlation and sensitivity of CLI to PET is critical to progress this technique further for use in high-throughput screening of pharmaceutical compounds. To achieve this milestone, it must first be established that CLI data correlate to PET data in an in vivo preclinical antitumor study. We used MLN4924, a phase 2 oncology therapeutic, which targets and inhibits the NEDD8-activating enzyme pathway involved in the ubiquitin–proteasome system. We compared the efficacious effects of MLN4924 using PET and Cerenkov luminescence image values in the same animals.

The frequency spectrum of Cherenkov radiation by a particle is given by the Frank–Tamm formula. Unlike fluorescence or emission spectrathat have characteristic spectral peaks, Cherenkov radiation is continuous. Around the visible spectrum, the relative intensity per unit frequency is approximately proportional to the frequency. That is, higher frequencies (shorter wavelengths) are more intense in Cherenkov radiation. This is why visible Cherenkov radiation is observed to be brilliant blue. In fact, most Cherenkov radiation is in the ultravioletspectrum—it is only with sufficiently accelerated charges that it even becomes visible; the sensitivity of the human eye peaks at green, and is very low in the violet portion of the spectrum.

There is a cut-off frequency above which the equation cos θ = 1 / (nβ) cannot be satisfied. Since the refractive index is a function of frequency (and hence wavelength), the intensity does not continue increasing at ever shorter wavelengths even for ultra-relativistic particles (where v/capproaches 1). At X-ray frequencies, the refractive index becomes less than unity (note that in media the phase velocity may exceed cwithout violating relativity) and hence no X-ray emission (or shorter wavelength emissions such as gamma rays) would be observed. However, X-rays can be generated at special frequencies just below those corresponding to core electronic transitions in a material, as the index of refraction is often greater than 1 just below a resonance frequency (see Kramers-Kronig relation and anomalous dispersion).

As in sonic booms and bow shocks, the angle of the shock cone is directly related to the velocity of the disruption. The Cherenkov angle is zero at the threshold velocity for the emission of Cherenkov radiation. The angle takes on a maximum as the particle speed approaches the speed of light. Hence, observed angles of incidence can be used to compute the direction and speed of a Cherenkov radiation-producing charge.


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