Lung perfusion imaging in nuclear medicine with 99mTc: a comprehensive survey of radiopharmaceuticals

BACKGROUND: Technetium-99 m-labeled macroaggregated albumin ([⁹⁹ᵐTc]Tc-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 [⁹⁹ᵐTc]Tc-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.