Minimising the impact of stable 208Pb on recovery of 212Pb from a generator

Abstract

Background: Stable ²⁰⁸Pb will accumulate over time in all ²¹²Pb generators, forming an increasing proportion of the Pb atoms and potentially impacting the efficiency of chelation of ²¹²Pb. This paper models the accumulation of ²⁰⁸Pb in ²¹²Pb-parent generators with time, calculates the optimal elution time with respect to effective specific activity (ESA) of the ²¹²Pb produced, and considers whether the presence of ²⁰⁸Pb could prevent the required molar activities (A_m) being achieved. A matrix calculation was utilised to model the decay of ²²⁴Ra and ²²⁸Th parents in generators and the associated accumulation of ²⁰⁸Pb with time. This model was used to calculate the optimal elution times for each generator with respect to ESA and A_m.

Results: The optimal elution time with respect to A_m of ²¹²Pb is 16.5 h for a ²²⁴Ra generator (61.0% of ²²⁴Ra starting activity, A_m = 6997 MBq ²¹²Pb/nmol total Pb) and 19.2 h for a ²²⁸Th generator (71.4% of ²²⁸Th starting activity, A_m = 6566 MBq ²¹²Pb/nmol total Pb).

Conclusions: The limited data available in literature shows the level of ²⁰⁸Pb present in these studies does not prevent attainment of the required molar activities for pre-clinical or clinical work. However, with other chelators and under other conditions this may not be the case. The authors would encourage others to measure and report the level of ²⁰⁸Pb in ²¹²Pb generator eluates alongside radiolabelling results and the max A_m of the radiopharmaceutical ²¹²Pb (vector molecule (VM)) achieved.

Keywords: Lead; Molar activity; Radiolabelling; Specific activity; Stable lead.

Fig. 1

Decay chain of ²²⁸Th down to stable ²⁰⁸Pb, half-life data taken from JEFF 3.3 database

Fig. 2

Atoms of ²⁰⁸Pb and ²¹²Pb growing into a ²²⁴Ra generator (assumed 350 MBq starting activity of ²²⁴Ra) against time (h) using both FISPIN and Matrix tools

Fig. 3

Percentage of Pb atoms present as ²¹²Pb on ²²⁴Ra (light blue) and ²²⁸Th (dark blue) generators, and molar activity (A_m) with time (h) from previous elution, calculated using the matrix tool. Independent of generator size

Fig. 4

a Percentage ingrown activity relative to starting ²²⁴Ra activity on secondary axis, b Molar activity of ²¹²Pb eluate (MBq ²¹²Pb/nmol Pb), c mean progress function of the ²¹²Pb grow-in versus time f(A,t), c mean progress function of the ²¹²Pb grow-in versus effective specific activity f(A,ESA), d plotted against grow-in time (h)

Fig. 5

a Percentage ingrown activity relative to starting ²²⁸Th activity on secondary axis, b Molar activity of ²¹²Pb eluate (MBq ²¹²Pb/nmol Pb), c mean progress function of the ²¹²Pb grow-in versus time f(A,t), d mean progress function of the ²¹²Pb grow-in versus effective specific activity f(A,ESA), all plotted against grow-in time (h)

Fig. 6

Grow-in time required for the elution of 500 MBq ²¹²Pb (primary axis), and A_m (GBq/nmol) of eluted ²¹²Pb (secondary axis), from various sized ²²⁸Th generators

Fig. 7

Proportion of Pb atoms present as ²¹²Pb and ²⁰⁸Pb where daughters are included (²¹²Pb-red, ²⁰⁸Pb-blue) and excluded (²¹²Pb-purple, ²⁰⁸Pb-green), with time (h) following elution from a ²²⁴Ra (size independent) generator after a 15.6 h grow-in period of ²¹²Pb all plotted on the primary axis. A_m of ²¹²Pb eluate where daughters are included (black) and excluded (orange) plotted on the secondary axis

Fig. 8

Proportion of Pb atoms present as ²¹²Pb and ²⁰⁸Pb where daughters are included (²¹²Pb-red, ²⁰⁸Pb-blue) and excluded (²¹²Pb-purple, ²⁰⁸Pb-green), with time (h) following elution from a ²²⁴Ra (size independent) generator after a 48.0 h grow-in period of ²¹²Pb all plotted on the primary axis. A_m of ²¹²Pb eluate where daughters are included (black) and excluded (orange) plotted on the secondary axis