Application of single SPECT/CT and Cerenkov luminescence for imaging of therapeutic isotopes

Therapeutic radionuclides are not easily visualised and are paired with positron (β+) or gamma-emitting radionuclides to evaluate disease progression using conventional nuclear imaging techniques (positron emission tomography [PET]; single photon computed tomography [SPECT]). Popular theranostic pairs include 68Ga/177Lu, 68Ga/255Ac, 64Cu/67Cu or 188Re/99mTc. Single photon computed tomography imaging of therapeutic isotopes is not routinely used because of the generally low yield in gamma emissions of these isotopes. However, technological advances in SPECT imaging hardware and software have made imaging of these tracers more feasible. Cerenkov-derived luminescence imaging (CLI) detects light emitted because of charged particles from radioactive decay moving faster than light in a medium; therefore, CLI is suitable to directly visualise beta-emitting therapeutic radionuclides. This aspect should be utilised more to support clinically relevant questions. This study evaluated SPECT and CLI-capabilities of three, relatively unused, therapeutic nuclides (186Re, 188Re, 109Pd) in comparison to already evaluated therapeutic nuclides (177Lu,131I) and diagnostic (68Ga, 64Cu, 18F, 89Zr) nuclides for application of theranostic radiopharmaceuticals. Single photon computed tomography/computed tomography – each isotope was calibrated according to manufacturer specifications using a multi-pinhole collimator. Images for all radionuclides were acquired using Derenzo and PET National Electrical Manufacturers Association (NEMA) phantoms. Following image reconstruction, the images were evaluated according to: sensitivity, resolution, uniformity and contrast signal-to-noise ratio (SNR). Cerenkov-derived luminescence imaging – A 1:2 dilution series of each radionuclide (1 mL in saline) was pipetted into a 24-well plate (activity 0–9.16 MBq/mL). Each radionuclide underwent CLI at half-life appropriate time points. Radionuclides were compared with respect to activityconcentration (kBq/μL) and average radiance (p/s/cm2/sr). Single photon computed tomography/computed tomography – Isotopes with gamma rays in the vicinity of 140 keV showed the best sensitivity and resolution (188Re and 186Re); visual uniformity of Rhenium-188 was superior to Rhenium-186. Compared to 177Lu and 131I evaluation of the SNR of 186Re- and 188Re-isotopes and 109Pd correlated as expected. Cerenkov-derived luminescence imaging – Linear regression and range analysis for all nuclides indicated a strong, positive correlation between the light emission intensity and activity concentration (R = 0.99). High energy emissions of 188Re (Eβmax = 2.10 MeV; Eβ(ave) = 0.8 MeV; 70% intensity) corresponded to radiance observed for 68Ga (Eβmax = 1.89 Mev; Eβave = 0.8 MeV; 87% intensity) while radiances for 109Pd and 186Re were 2.5- and 5-fold lower, respectively (all other nuclides ≤15-fold lower). Rhenium-186/-188 exhibits superior SPECT imaging capabilities over 131I- and 177Lu-radionuclides while 109Pd still provides suitable SPECT images. All three therapeutic isotopes have excellent CLI properties comparable to other therapeutic-/PET-isotopes. The SPECT- and-CLI imaging capabilities of these therapeutic radionuclides allow for further research into more comprehensive targeting mechanism. (authors)