Enhanced Detection of Weakly-Penetrating Alpha Radiation via Thin Layer Chromatography

Introduction: Targeted Alpha Therapy is regarded as having potential advantages in the treatment of cancer due to the alpha particle’s extremely short range in tissue - on the scale of cellular dimensions - which results in highly localized deposition of energy in vivo and consequent tumor-cell killing ability without harming nearby tissue. But this same property renders the alpha-emitters difficult to detect directly with commonly-available instrumentation. For quality-assurance assay of alpha-labeled radio-pharmaceuticals via radio-thin-layer chromatography (RTLC), it is common practice to utilize lower-energy beta or photon-emissions accompanying the alpha-emissions, which may be technically easier to detect, but at relatively poor overall signal-to-noise - i.e., signal-to-fluctuation ratio.

Objectives: We are developing an enhanced version of our OmniRad thin-layer chromatography beta-detector module to directly detect alpha-particles. The energy deposited in the detector by an alpha particle is more than an order of magnitude greater than corresponding photon or beta events, potentially yielding significantly greater signal-to-noise ratio in the chromatography trace while requiring correspondingly lower amounts of (expensive!) nuclide to be expended for quality-assurance.

Methods: A proof-of-principle prototype was adapted from our standard OmniRad current mode beta-detector module, in which the radiation-induced photo-current generated in a 10 x 10 mm Si PIN photo-diode is amplified in a current-to-voltage converting amplifier with nominal trans-resistance gain of 5 x 10^9 ohms. Since alpha’s cannot penetrate the protective polymer window coating on a standard photo-diode, a special ‘windowless’ Si PIN photo-diode is employed. A very thin (0.1 mil) aluminized mylar entrance window shields the photo-diode from ambient room light and electromagnetic interference, while allowing alpha’s to penetrate. This prototype module is currently being field tested at the University of Utah, courtesy of Prof. Tara Mastren, utilizing the alpha-emitting nuclide 225Ac (t1/2 = 10 days) which is embedded in silicon nano-particles * . In the meantime, a second, more advanced prototype detector module is being developed and evaluated in our lab using small check sources - 138 day 210 Po. This version of the detector module employs pulse-mode detection rather than current mode detection. Pulse-mode operation allows incorporation of a threshold discriminator which eliminates baseline fluctuation due to electronic noise and drift, as well as most interference from ambient photon background radiation, thereby extending the lower-limit of detectability for alpha’s. Results and Conclusions: The ‘current mode’ alpha-prototype detector module being field tested at the University of Utah has demonstrated reliable detection and display of a main peak corresponding to a ~75 nCi ‘spot’ and a smaller subsequent peak corresponding to ~ 7.5 nCi free 225Ac. At this level of activity on the TLC plate, beta or photon detection mode hardly shows any response at all above the background using a ‘standard’ OmniRad beta mode PIN diode detector, though it should also be noted that each 225Ac decay is followed by a cascade of three alpha-and beta-emitting daughters, with a total alpha energy deposition of ~27 MeV. In any case, the minimum detectable signal peaks are ultimately governed by counting statistics and baseline fluctuation due to electronic noise and drift. Development continues in parallel in our lab using pulse-mode detection, eliminating effects of noise and baseline drift. *Reference: <https://netrf.org/2019/04/16/targeted-alpha-therapy-for-nets>