Measurements of 177mLu contaminants in Lutetium-Based Therapeutics

A practical approach is presented to reliably detect and quantify the long-lived contaminant 177mLu commonly found in 177Lu-based therapeutics.

The objective of this work was to provide methods to measure 177mLu on detector systems typically found in hospital environments that support theranostic programs.

Twenty-four samples (14 177Lu dotatate, 10 177Lu PSMA) were collected from unused patient vials. 1-mL aliquots were drawn from each vial for counting on a well-type, one-inch (2.5-cm) NaI detector and liquid scintillation counter (LSC) system that support the hospital theragnostic and radiation safety programs, respectively. Prior to measurement, all samples were counted on a well-type high-purity germanium detector (HPGe) to establish a quantification standard for comparison. All detectors were calibrated with known standards and counting durations were adjusted to achieve <5% error in the integrated photopeaks and beta spectra. Data were reported as percent ratio of 177mLu/177Lu.

The closely spaced photopeaks at 108 keV, 113 keV, and 122 keV were resolvable as a single peak on the NaI detector. For all 177Lu dotatate samples, the mean 177mLu/177Lu ratio was 6.22 × 10-3 +/- 1.32 × 10-3 % on the NaI well, which agreed with HPGe well at 5.86 × 10-3 +/- 1.73 × 10-3 %. The 177mLu/177Lu ratio from the LSC was higher at 8.49 × 10-3 +/- 1.96 × 10-3 % due to contributions from multiple beta decay transitions that could not be resolved. For all 177Lu PSMA samples, the mean 177mLu/177Lu ratio was four orders of magnitude lower than 177Lu dotatate with no observable photopeaks on the HPGe or NaI well detectors. Similarly the ratio from LSC measurements on 177Lu PSMA were at least three orders of magnitude lower than 177Lu dotatate.

This work demonstrated that, some but not all, 177Lu-based therapeutics contain measurable amounts of 177mLu and the presence of this contaminant depends on the radioisotope production method. Spectroscopy methods using well-type and liquid scintillation systems can detect 177mLu but the liquid scintillation system could not quantify the total amount due to its inability to separate beta decay events from 177mLu and 177Lu decay. None of the measurements made with the well-type detectors on samples from 177Lu PSMA exceeded the minimum detectable activity for 177mLu.