Preclinical SPECT-CT imaging studies with cyclotron produced Tc-99m

This work reports results of a preclinical study aimed at evaluating the diagnostic quality of radiopharmaceuticals prepared using cyclotron-produced Tc-99m as compared to generator-produced Tc-99m analogues. Material and methods: Enriched (99.05%) Mo-100 metallic targets were irradiated with a proton beam having energies within the range 19−17 MeV. Purification of Tc-99m from the irradiated targets was carried out by solvent extraction using methyl-ethyl ketone (MEK) having a well-established selective affinity for the pertechnetate ion. Further chromatographic purification afforded Tc-99m in physiological solution that was subsequently employed for the preparation of a number of Tc-99m radiopharmaceuticals for perfusion cardiac and brain imaging. Radionuclidic purity (RNP) of the Tc-eluate was measured by γ-spectrometry and radiochemical purity (RCP) of Tcradiopharmaceuticals was checked by radio-TLC and HPLC. Anesthetized Wistar rats were injected into the jugular vein and in vivo whole-body SPECT-CT images were collected with a hybrid YAP(S)PET-CT small-animal scanner. SPECTimages were corrected for injection time and activity. Results: Radionuclidic purity of accelerator-produced Tc-99m was in the range 99.3 ± 0.2% at the end of bombardment (EOB) and 99.5 ± 0.2% at the end of chemical extraction (6 hours after EOB). Main radionuclidic impurities originated from the presence of the γ-emitting Tc-isotopes Tc-93, Tc-94g, Tc-95g and Tc-96g. This caused a detectable scatter effect on SPECT images mostly generated by the interaction of these parasite γ- rays with the high-resolution collimator of the small-animal scanner. For this reason, a scatter-correction method, based on the definition of different energy ranges, was implemented on these images. Considering the efficiency of the correction approach and the high-capacity of biological sites targeted by Tc-99m perfusion imaging agents, the impact on the image quality was negligible when compared with the same images collected with generator-produced Tc-99m. Conclusions: In vivo SPECT-CT preclinical imaging study in a rat animal model using a high-resolution small-animal scanner confirmed a superimposable biodistribution behavior of heart and brain perfusion Tc-99m radiopharmaceuticals labeled with both cyclotron- and generator-produced Tc-99m. However, it should be noted that the effect of scattered high-energy γ-rays, generated by the decays of technetium radioisotopes impurities in cyclotron-produced Tc-99m, strongly depends on the specific imaging system and, therefore, extrapolation to images obtained with available SPECT cameras for human studies is not straightforward. This points to the need of conducting dedicated imaging tests with conventional SPECT imaging equipment employed in a clinical setting.