Radio-LC-MS for the Characterization of 99mTc-Labeled Bioconjugates

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Abstract
This report describes the first example of using radio-LC-MS for determining the composition of 99mTc radiopharmaceuticals at the tracer level. The in-line radiometric detector is a useful addition to a standard LC-MS and provides direct correlation between the MS data and the radioactive species in a radiopharmaceutical kit. Complexes [99mTc(HYNICtide)(tricine)(L)] (RP444, L = TPPTS; RP445, L = TPPDS; and RP446, L = TPPMS) were prepared using a decayed generator eluant. All the ternary ligand 99mTc complexes show the expected monoprotonated molecular ions, (M + 1)+, and diprotonated molecular ions, (M + 2)2+. The LC-MS spectral data support the proposed structure and are consistent with those obtained for their corresponding 99Tc analogues. Ternary ligand complexes [99mTc(HYNICtide)(tricine)(L)] (L = ISONIC-HE and ISONIC-Sorb) are neutral, and the molecular weights are also lower than that of RP444. Using a fresh generator eluant (24 h prior elution), only 1−2 mCi of 99mTc [(7 × 10-12)−(1.5 × 10-11) mol of technetium complex] are required to obtain a reasonably clean mass spectrum. Radio-LC-MS is a quick and accurate analytical tool for characterization of 99mTc radiopharmaceuticals at the tracer level.