Gamma camera imaging characteristics of 203/212Pb as a theragnostic pair for targeted alpha therapy: a feasibility study.

Abstract

Background: ²⁰³Pb and ²¹²Pb show promise as theragnostic agents for targeted alpha therapy (TAT) because two chemically identical isotopes can be used for diagnostic imaging and treatment. In the ²¹²Pb decay chain, in addition to alpha and beta particles, a large number of photons are emitted, those with an energy of 239 keV and the characteristic X-rays of ²¹²Pb could be used for imaging. ²⁰³Pb decays by photon emission with an energy of 279 keV, which appears suitable for gamma camera imaging. The aim of this study was to investigate suitable imaging protocols and to characterize the scintigraphic imaging properties and their implications for the clinical feasibility as theragnostic isotopes.

Methods: Planar and SPECT/CT images were obtained with medium- and high-energy collimators on a Siemens Symbia Intevo 6 using a NEMA image quality phantom in various phantom setups and another body-shaped phantom with several inserts. Different energy windows were investigated and measurements were evaluated in terms of sensitivity, count rate performance, spatial resolution, contrast recovery, lesion detectability, and image quantification.

Results: Evaluation of image quality showed superior imaging characteristics for ²⁰³Pb compared to ²¹²Pb regarding spatial resolution, contrast recovery, image noise, and quantification accuracy. Both medium- and high- energy collimators were suitable for ²⁰³Pb imaging, with the medium energy collimators showed slightly better imaging properties. Images obtained with the HE collimators in the 79 keV energy window showed the best visual image quality for ²¹²Pb. Due to high-energy photon emissions from ²¹²Pb daughter nuclides (e.g., 2.6 MeV from ²⁰⁸Tl), dead time related count losses occurred even at low activities (20% count loss at 20 MBq for MELP collimators).

Conclusions: According to our results and first-in-human imaging studies, SPECT/CT imaging with the ^203/212Pb theragnostic pair is clinically feasible. ²⁰³Pb is an appropriate imaging surrogate to investigate pharmacokinetics and perform predictive dosimetry. The less favorable imaging characteristics of ²¹²Pb make image quantification and post-treatment dosimetry challenging and require further research.