Cartilage-Specific ¹⁸F-NaF Uptake in Rat Models: A Multimodal In Vitro and Ex Vitro Comparative Study with ^99mTc-MDP

Background:¹⁸F-NaF and ^99mTc-MDP are widely used bone imaging tracers, but their comparative uptake in bone versus cartilage is unclear. This study aimed to directly compare these patterns in rats to guide musculoskeletal molecular imaging. Methods: Male Sprague-Dawley rats underwent in vivo and ex vivo radiotracer studies. Tracer uptake (%ID/g) was quantified in bone and cartilage at 30, 60, or 120 min post-injection (¹⁸F-NaF or ^99mTc-MDP), and across different ages. Additional rats received subcutaneous implants of viable or devitalized bone and cartilage; uptake was assessed using PET/CT, autoradiography, and histology. Results:¹⁸F-NaF showed faster blood/background clearance and higher target-to-background ratios compared to ^99mTc-MDP, especially in weight-bearing joint cartilage. ¹⁸F-NaF uptake in cancellous bone significantly exceeded that of ^99mTc-MDP, whereas ^99mTc-MDP showed higher uptake in knee cartilage. Age-related analysis showed maximal knee cartilage accumulation in aged rats. Histological and cell inactivation studies confirmed that ¹⁸F-NaF uptake reflects both cellular activity and degree of calcification. Conclusions:¹⁸F-NaF demonstrates distinctive, quantifiable uptake in cartilage, dependent on both cellular activity and calcification, and exhibits favorable imaging characteristics versus ^99mTc-MDP for cartilage metabolism. These findings support ¹⁸F-NaF as a promising tool for early diagnosis and therapeutic monitoring of bone and joint disorders, and provide pathophysiological insight into the dynamics of the bone-cartilage interface.