Quantitative Comparison of SPECT and PET Performance for Clinical Theranostic Applications

Radiopharmaceutical therapy is an emerging approach to treat metastatic disease, with the potential to enable personalized care through imaging. With the growing interest in quantitative imaging, there remains a need for systematic assessment of imageable radionuclides and scanner performance under comparable conditions. This motivated us to quantitatively and qualitatively compare SPECT and PET performance using standardized evaluation procedures to assess their effectiveness in imaging applications for targeted radiotherapy. Methods: The National Electrical Manufacturers Association International Electrotechnical Commission body phantom was used to assess recovery coefficients, contrast, and image quality, including spatial resolution and noise. SPECT performance was evaluated using ^99mTc (a low-energy γ-ray-emitting isotope), ²⁰³Pb (a surrogate for the therapeutic α-particle-emitting ²¹²Pb), and theranostic ¹⁷⁷Lu. PET performance was tested using ¹⁸F, ⁸⁹Zr, and ⁶⁴Cu as imaging surrogates. Results: PET demonstrated superior spatial resolution and accurate activity recovery compared with SPECT, which was limited by lower sensitivity, photon scatter, and collimator design constraints. Among PET isotopes, ¹⁸F showed consistently high quantitative accuracy, whereas ⁸⁹Zr and ⁶⁴Cu performed similarly, with only minor reductions in performance metrics. For SPECT, ^99mTc outperformed ²⁰³Pb and ¹⁷⁷Lu in both lesion detectability and activity recovery. ²⁰³Pb and ¹⁷⁷Lu showed poor quantitative accuracy; however, increasing iterations in reconstruction improved results. Conclusion: These findings underscore the importance of selecting appropriate imaging modalities, isotopes, and reconstruction parameters for theranostic applications. Limitations in quantitative accuracy must be addressed and acknowledged in the search for precise and effective treatment strategies. This study also demonstrates that ²⁰³Pb may serve as a suitable diagnostic partner to ²¹²Pb and validates the use of these quantitative methodologies for the evaluation of PET and SPECT imaging tasks.