Ga-labeled fibroblast activation protein (FAP) inhibitor ( 68 Ga-FAPI) PET targets 68 Ga-FAPI-positive activated fibroblasts and is a promising imaging technique for various types of cancer and nonmalignant pathologies. However, discrimination between malignant and nonmalignant 68 Ga-FAPI-positive lesions based on static PET with a single acquisition time point can be challenging. Additionally, the optimal imaging time point for 68 Ga-FAPI PET has not been identified yet, and different 68 Ga-FAPI tracer variants are currently used. In this retrospective analysis, we evaluate the diagnostic value of repetitive early 68 Ga-FAPI PET with 68 Ga-FAPI-02, 68 Ga-FAPI-46, and 68 Ga-FAPI-74 for malignant, inflammatory/reactive, and degenerative lesions and describe the implications for future 68 Ga-FAPI imaging protocols. Methods: Whole-body PET scans of 24 cancer patients were acquired at 10, 22, 34, 46, and 58 min after the administration of 150-250 MBq of 68 Ga-FAPI tracer molecules (8 patients each for 68 Ga-FAPI-02, 68 Ga-FAPI-46, and 68 Ga-FAPI-74). Detection rates and SUVs (SUV max and SUV mean ) for healthy tissues, cancer manifestations, and nonmalignant lesions were measured, and target-to-background ratios (TBR) versus blood and fat were calculated for all acquisition time points. Results: For most healthy tissues except fat and spinal canal, biodistribution analysis showed decreasing uptake over time. We analyzed 134 malignant, inflammatory/reactive, and degenerative lesions. Detection rates were minimally reduced for the first 2 acquisition time points and remained at a constant high level from 34 to 58 min after injection. The uptake of all 3 variants was higher in malignant and inflammatory/reactive lesions than in degenerative lesions. 68 Ga-FAPI-46 showed the highest uptake and TBRs in all pathologies. For all variants, TBRs versus blood constantly increased over time for all pathologies, and TBRs versus fat were constant or decreased slightly. Conclusion: 68 Ga-FAPI PET/CT is a promising imaging modality for malignancies and benign lesions. Repetitive early PET acquisition added diagnostic value for the discrimination of malignant from nonmalignant 68 Ga-FAPI-positive lesions. High detection rates and TBRs over time confirmed that PET acquisition earlier than 60 min after injection delivers high-contrast images. Additionally, considering clinical feasibility, acquisition at 30-40 min after injection might be a reasonable compromise. Different 68 Ga-FAPI variants show significant differences in timedependent biodistributional behavior and should be selected carefully depending on the clinical setting.
The purpose of this study was to analyze and evaluate a model of restricted water diffusion between equidistant permeable membranes for cell-size and permeability measurements in biological tissue. Based on the known probability distribution of diffusion distances after the diffusion time τ in a system of permeable membranes characterized by three parameters (membrane permeability P, membrane distance L, and free diffusivity D0), an equivalent dimensionless model was derived with a probability distribution characterized by only a single (dimensionless) tissue parameter [Formula: see text]. Evaluating this proposed model function, the dimensionless diffusion coefficient [Formula: see text] was numerically calculated for 60 values of the dimensionless diffusion time [Formula: see text] and 35 values of [Formula: see text]. Diffusion coefficients were measured in a carrot by diffusion-weighted magnetic resonance imaging (MRI) at 18 diffusion times between 9.9 and 1022.7 ms and fitted to the simulation results [Formula: see text] to determine L, P, and D0. The measured diffusivities followed the simulated dependence of [Formula: see text]. Determined cell sizes varied from 21 to 76 μm, permeabilities from 0.007 to 0.039 μm(-1), and the free diffusivities from 1354 to 1713 μm(2) s(-1). In conclusion, the proposed dimensionless tissue model can be used to determine tissue parameters (D0, L, P) based on diffusion MRI with multiple diffusion times. Measurements in a carrot showed a good agreement of the cell diameter, L, determined by diffusion MRI and by light microscopy.
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