We built a joint replacement loosening model based on the original rabbit model of infection and evaluated the performance characteristics of ¹⁸F-FDG and ⁶⁸ Ga-FAPI in evaluating infection and loosening. After surgery, the rabbits were divided into four groups, with six individuals in the control group and 10 each in the aseptic loosening, S. aureus and S. epidermidis groups. PET/CT and serological examination were performed three times at two-week intervals. After the rabbits were euthanized, micro-CT, tissue pathology, pullout tests and scanning electron microscopy (SEM) were performed. The pullout test and SEM showed the feasibility of the aseptic loosening model. ¹⁸F-FDG showed similar performance in the control and loosening groups. The SUVmax of the S. aureus group was consistently higher than that of the S. epidermidis group. As for ⁶⁸ Ga-FAPI, the SUVmax of the control group was lowest in the second week and gradually increased over subsequent weeks. The SUVmax of the loosening group began to exceed that of the control group after the second week. The SUVmax of the S. aureus group in the second week was the lowest among the four groups and increased as the number of weeks increased. The pathology results showed concordance with the performance of PET/CT. Linear regressions between SUVmax and serology showed that ¹⁸F-FDG was positively correlated with CRP and IL-6, while ⁶⁸ Ga-FAPI revealed negative correlations with CRP and IL-6 in the second week and positive correlations in the sixth week. In addition, the SUVmax and MT(target)V of both ¹⁸F-FDG and ⁶⁸ Ga-FAPI were negatively correlated with bone volume/trabecular volume (TV) and bone surface area/TV. In this longitudinal observation, ⁶⁸ Ga-FAPI showed greater sensitivity than ¹⁸F-FDG in detecting diseases, and ⁶⁸ Ga-FAPI had no intestinal or muscular uptake. The MT(target)V of ⁶⁸ Ga-FAPI was larger than that of ¹⁸F-FDG, which meant that ⁶⁸ Ga-FAPI had the potential to define the scope of lesions more accurately. Finally, the SUVmax of ⁶⁸ Ga-FAPI could not differentiate between loosening and infection; further study of the diagnostic criteria is warranted.

Objective: Currently, ⁶⁸Ga-labeled somatostatin analogs (SSAs) are the most commonly used imaging agents for patients with neuroendocrine tumors (NETs) in clinical practice, demonstrating good results in tumor diagnosis. For applications in peptide receptor radionuclide therapy (PRRT), targeted drugs should have high tumor uptake and prolonged tumor retention time. To enhance the uptake and retention of tracers in NETs, our goal is to design a ⁶⁸Ga-labeled heterodimer for optimizing pharmacokinetics and assess whether this form is more efficacious than its monomeric equivalents. Methods: Using the somatostatin analog TATE and quinoline-based compound FAPI-46 as raw materials, we designed and synthesized ⁶⁸Ga-labeled TATE-46. The labeling efficiency and stability were verified by Radio-HPLC. The receptor binding properties and tumor targeting were examined both in vitro and in vivo by using NCI-H727 (SSTR2/FAP, positive) and Mc38 (SSTR2/FAP, negative) cell lines and tumor-bearing mouse models. Preclinical evaluation was performed through cell uptake, pharmacokinetics, Micro PET, and biodistribution studies, and the results were compared with [⁶⁸Ga]Ga-DOTA-TATE and [⁶⁸Ga]Ga -FAPI-46. Immunohistochemistry and HE staining were performed on tumor tissues from tumor-bearing mice for further validation. Results: [⁶⁸Ga]Ga-TATE-46 showed comparable SSTR2 and FAP targeting ability to monomeric TATE and FAPI-46 in cell uptake and PET imaging studies. [⁶⁸Ga]Ga-TATE-46 exhibited significantly higher uptake in NCI-H727 (SSTR2/FAP, positive) tumors compared to [⁶⁸Ga]Ga-DOTA-TATE (p < 0.001) and [⁶⁸Ga]Ga-FAPI-46 (p < 0.001). No increased uptake of [⁶⁸Ga]Ga-TATE-46 was observed in MC38 tumors (SSTR2/FAP, negative). Additionally, excess DOTA-TATE and/or unlabeled FAPI-46 significantly blocked the uptake of [⁶⁸Ga]Ga-TATE-46 in NCI-H727 tumors (p < 0.001), confirming its dual-receptor targeting characteristics. The ex vivo biodistribution, immunofluorescence and immunohistochemistry results were in line with the in vivo imaging findings. Conclusion: Compared with ⁶⁸Ga-labeled FAPI-46 and DOTA-TATE mono-specific tracers, the dual-target tracer [⁶⁸Ga]Ga-TATE-46 improves tumor uptake, extends tumor retention, and enhances pharmacokinetics. It is an effective probe for non-invasive detection of tumors expressing FAP and SSTR2, and it is worth further studying its application in the expression of sstr2 and FAP-related tumors.

Purpose We built a loosening model based on the original infection model of rabbit and evaluated the performance characteristics of ¹⁸F-FDG and ⁶⁸Ga-FAPI in infection and loosening. Methods After surgery, the rabbits were divided into four groups, six in the control group and 10 in the loosening, S. aureus and S. epidermis groups. PET/CT and serological examination were performed every two weeks for three times. After sacrificed, micro-CT, tissue culture, pullout test and scanning electron microscope were performed. Results As for ¹⁸F-FDG, performances of control and loosening groups were similar. SUVmax of S. aureus had been consistently in the high range than that of S. epidermis. As for ⁶⁸Ga-FAPI, control group had the lowest SUVmax in the second week and increased gradually. SUVmax of loosening group began exceed control group since the second week. SUVmax of S. aureus in the second week was the lowest among four group and raised as the number of weeks increased and equalled to SUVmax of S. epidermis in the sixth week. Linear regressions between SUVmax and serology showed that ¹⁸F-FDG was positively correlated with CRP and IL-6 while ⁶⁸Ga-FAPI revealed negative and positive correlation with CRP and IL-6 in the second and sixth week. Besides, both SUVmax and MTV of ¹⁸F-FDG or ⁶⁸Ga-FAPI were negatively correlated with BV/TV and BS/TV. Conclusion In this longitudinal observation, ⁶⁸Ga-FAPI showed greater sensitivity than ¹⁸F-FDG in detecting diseases, and ⁶⁸Ga-FAPI had not intestinal and muscular uptake. MTV of ⁶⁸Ga-FAPI were larger than ¹⁸F-FDG, which meant that ⁶⁸Ga-FAPI had the potential to define the scope of lesions more accurately. Finally, SUVmax could not differentiate loosening and infection in ⁶⁸Ga-FAPI, further study about diagnostic criteria was warranted.