H N Wang, C K Huang, Y E Huang, Y T Huang, S H Chan, J R Tseng
Our findings suggest that 68Ga-FAPI and 18F-FDG may offer the highest estimated DRs for bone and soft tissue infection and inflammation, while 99mTc-HMPAO-WBC appears to perform best among scintigraphy probes. The observation that 68Ga-citrate ranked below several conventional tracers suggests that detection performance may depend not only on the imaging platform but also on the biological targeting mechanism of the radiopharmaceutical. Given the limited number of studies, these rankings should be interpreted with caution and warrant further validation in large-scale comparative trials.
INTRODUCTION AND OBJECTIVE: The optimal radiotracer for detecting infection and inflammation remains uncertain due to limited direct comparative data. This systematic review and network meta-analysis (NMA) aimed to evaluate and rank the diagnostic performance of various positron emission tomography (PET) and conventional nuclear medicine tracers in bone and soft tissue.
METHODS: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were systematically searched through February 2026 for studies comparing at least two radiotracers for infection or inflammation detection. The outcome was the DR. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a frequentist random-effects NMA with 67Ga-citrate as the reference node.
RESULTS: Thirteen studies involving 558 subjects and lesions were included, forming a network of 10 radiotracers (three PET and seven conventional scintigraphy probes). Relative to 67Ga-citrate, 68Ga-FAPI had the highest estimated DR (RR 1.94; 95% CI, 0.88-4.30), followed by 18F-FDG (RR 1.63; 95% CI, 0.81-3.26), however, neither difference reached statistical significance. Among conventional agents, 99mTc-DMSA(V) and 99mTc-HMPAO-WBC ranked highest, whereas 99mTc-nanocolloid yielded a lower DR than the reference (RR 0.69; 95% CI, 0.48-0.99). 99mTc-MDP had the lowest DR in the network (RR 0.64; 95% CI, 0.38-1.07). The third PET tracer, 68Ga-citrate, ranked seventh - below several conventional scintigraphy agents.
CONCLUSION: Our findings suggest that 68Ga-FAPI and 18F-FDG may offer the highest estimated DRs for bone and soft tissue infection and inflammation, while 99mTc-HMPAO-WBC appears to perform best among scintigraphy probes. The observation that 68Ga-citrate ranked below several conventional tracers suggests that detection performance may depend not only on the imaging platform but also on the biological targeting mechanism of the radiopharmaceutical. Given the limited number of studies, these rankings should be interpreted with caution and warrant further validation in large-scale comparative trials.