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Background <p>Technetium-99&#xa0;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.</p> Main body <p>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.</p> Conclusion <p>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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月31日

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  • Hassan Zareian,
  • Mehrnaz Mardazad,
  • Mahshid Kiani,
  • Nafise Pourshafagh,
  • Fateme Karimi,
  • Mehdi Shafee Ardestani

摘要

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.

Graphical Abstract