Background and purpose The 68Ga-labeled nanobody SNA006 marks a significant advancement in noninvasive ImmunoPET imaging of CD8+ T cells, facilitating real-time tracking of cellular immune responses in cancer, yet its pharmacokinetic properties remain suboptimal. This study aimed to develop a next-generation CD8-targeting immunoPET nanobody probe by incorporating a PEGylated brush border membrane enzyme-cleavable linker to improve pharmacokinetics and to evaluate its characterization in CD8-positive intrapulmonary tumors. Experimental approach A precursor based on SNA006, containing a PEGylated brush border membrane enzyme-cleavable linker, was designed, synthesized, and radiolabeled with gallium-68 to yield 68Ga-NOTA-m-SNA006. The probe was subsequently assessed both in vitro and in vivo. Key results The probe exhibited high radiochemical yield, purity, and favorable stability, and demonstrated binding to the CD8 protein with high affinity. PET/CT imaging and biodistribution studies revealed that 68Ga-NOTA-m-SNA006 exhibited favorable pharmacokinetic properties, including rapid clearance from the kidneys, reduced liver uptake, and sustained retention in the tumor, compared with 68Ga-NODAGA-SNA006. 68Ga-NOTA-m-SNA006 exhibited high uptake in lung lesions during in vivo PET imaging, reflecting CD8 expression in an intrapulmonary tumor model. Conclusion and implication In summary, we present a novel 68Ga-labeled SNA006 radiotracer with an optimized linker moiety, 68Ga-NOTA-m-SNA006, which effectively decreases renal and hepatic uptake while maintaining tumor uptake, thereby enhancing the tumor-to-background ratio. This approach represents a critical advancement in addressing the persistent challenge of radioactivity in the kidneys and liver associated with nanobody-based radiopharmaceuticals.

Purpose: Parkinson’s disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons in the brain. To achieve better explorations of dopamine changes both centrally and peripherally, we employed uEXPLORER dynamic [11C]CFT PET/CT imaging combined with voxel-wise kinetic modeling. Methods: Eleven participants (five patients, PD and six healthy volunteers, HC) underwent 75-min dynamic scans were enrolled. Volumes of interest for four nigrostriatal nuclei (caudate, putamen, pallidum and substantial nigra) and three digestive organs (pancreas, stomach and duodenum) were delineated. Total-body parametric images of relative transporter rate constant (R1) and distribution volume ratio (DVR) using the simplified reference tissue model (SRTM2) were quantitatively generated by a linear regression with spatial-constraint algorithm. Standardized uptake value ratio (SUVR) at early and late phase were calculated as the semi-quantitative substitutes. Results: Significant differences between the two groups were identified in DVR and SUVRLP of putamen (P < 0.05) and SUVREP of stomach (P < 0.01). For HC group, negative correlations of R1 were achieved between stomach and both putamen and substantial nigra (all P < 0.05); positive correlations of DVR were identified between pancreas and all four brain nuclei (all P < 0.05). Yet in PD group, correlations of R1 or DVR between the targeted digestive and brain areas were considerably diminished. Similar trends in correlations were also found in SUVR analysis. Conclusions: We introduced a pioneering approach using dynamic total-body [11C]CFT PET/CT imaging to investigate distinctive patterns of potential “brain-GI” interplays, which may provide new insights towards the understanding of PD.