In-target production of [11C]CH4 from a nitrogen/hydrogen gas target as a function of beam current, irradiation time, and target temperature

Abstract

Background: Production of [¹¹C]CH₄ from gas targets is notorious for weak performance with respect to yield, especially when using high beam currents. Post-target conversion of [¹¹C]CO₂ to [¹¹C]CH₄ is a widely used roundabout method in ¹¹C-radiochemistry, but the added complexity increase the challenge to control carrier carbon. Thus in-target-produced [¹¹C]CH₄ is superior with respect to molar activity. We studied the in-target production of [¹¹C]CO₂ and [¹¹C]CH₄ from nitrogen gas targets as a function of beam current, irradiation time, and target temperature.

Results: [¹¹C]CO₂ production was practically unchanged across the range of varied parameters, but the [¹¹C]CH₄ yield, presented in terms of saturation yield Y_SAT(¹¹CH₄), had a negative correlation with beam current and a positive correlation with target chamber temperature. A formulated model equation indicates behavior where the [¹¹C]CH₄ formation follows a parabolic graph as a function of beam current. The negative square term, i.e., the yield loss, is postulated to arise from Haber-Bosch-like NH₃ formation: N₂ + 3H₂ → 2NH₃. The studied conditions suggest that the NH₃ (liq.) would be condensed on the target chamber walls, thus depleting the hydrogen reserve needed for the conversion of nascent ¹¹C to [¹¹C]CH₄.

Conclusions: [¹¹C]CH₄ production can be improved by increasing the target chamber temperature, which is presented in a mathematical formula. Our observations have implications for targetry design (geometry, gas volume and composition, pressure) and irradiation conditions, providing specific knowledge to enhance [¹¹C]CH₄ production at high beam currents. Increased [¹¹C]CH₄ radioactivity is an obvious benefit in radiosynthesis in terms of product yield and molar radioactivity.

Keywords: Carbon-11; Haber–Bosch; PET; Targetry; [11C]methane.

Fig. 1

Target chamber. Dimensions in millimeters. A Front flange for target chamber. The grid structure and cooling channels drilled into the front piece are displayed in the cutaway drawing. B Front view (left) and cutaway drawing (right)

Fig. 2

Saturation yields, Y_SAT [GBq/µA], calculated from the measured second category data (Additional file 1: Table S3) as a function of target chamber temperature and beam current. Dashed lines show linear fit for Y_SAT(¹¹CO₂) and Y_SAT(¹¹CH₄) at various target chamber temperatures. The theoretical saturation yield of ¹¹C for the given proton energy, uncorrected for the N₂-H₂ composition, is indicated with a horizontal dashed line. A Saturation yield of ¹¹C-carbon dioxide, i.e., Y_SAT(¹¹CO₂). B Saturation yield of ¹¹C-methane, i.e., Y_SAT(¹¹CH₄). The y-axis intersections of the linear fit equations (constant term k) were used to determine the constant b in Eq. 2b

Fig. 3

Temperature-dependent factor k(T) for [¹¹C]CH₄ production. Scatter plot data points are from the experimental Y_SAT(¹¹CH₄) data (Fig. 2B), incorporating the constant terms k of the linear-fit equations. The linear fit here is forced through zero, and the slope gives the constant b (Eq. 2b)

Fig. 4

Radioactivity at EOB as a function of irradiation time at a constant 40 °C target chamber temperature for nominal beam currents: A 10 µA, B 20 µA, and C 40 µA. Theoretical ¹¹C radioactivity A_EOB(¹¹C) (□), measured [¹¹C]CH₄ radioactivity A_EOB(¹¹CH₄) (○), and predicted ¹¹CH₄ radioactivity cA_EOB(¹¹CH₄), calculated according to model Eq. 2d (∆)

Fig. 5

Predicted ¹¹CH₄ radioactivity cA_EOB(¹¹CH₄) for 40-min irradiation across a beam current range at various target chamber temperatures, calculated according to model Eq. 2d

Fig. 6

Ammonia phase diagram. Irradiation conditions (×) of [¹¹C]CH₄ production in this study, i.e., beam-on pressure and target chamber temperature