Abstract Background Technetium-99 m–labeled macroaggregated albumin (⁹⁹ᵐTcTc-MAA) is the standard agent for lung perfusion imaging in pulmonary embolism (PE). Limitations related to particle consistency, preparation procedures, and blood-derived origin have prompted the development of alternative non-blood-derived tracers. Main body A narrative review of studies up to August 2025 was performed. Candidate radiopharmaceuticals were evaluated for pulmonary localization, physicochemical properties, quality control characteristics, radiopharmacy practicality, kit-based preparation, and preclinical or clinical validation. Biodegradable microspheres, synthetic colloids, starch-based microparticles, and small-molecule complexes demonstrated promising lung uptake. Most tracers, however, lacked standardized preparation, kit compatibility, or validation in PE-relevant models. Starch-based microparticles emerged as the most translationally promising, showing practical workflow and favorable biodistribution. Conclusion No non-blood-derived ⁹⁹ᵐTc tracer currently matches ⁹⁹ᵐTcTc-MAA for routine lung perfusion imaging. Future development requires standardized, pharmacopeia-aligned tracers, head-to-head comparisons, and systematic evaluation in early-phase clinical trials. Graphical Abstract
Zareian et al. (Tue,) studied this question.
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