Beyond discovery: are we understanding PET tracers as fast as we invent them? a critical review

Abstract Background The field of nuclear medicine is experiencing an unprecedented proliferation of novel positron emission tomography (PET) tracers, with FDA-approved PET tracers increasing by 75% between 2020 and 2023 (from 12 to 21 agents). While this innovation promises to advance molecular imaging and personalized medicine, it raises critical questions about whether our biological understanding, validated clinical interpretation frameworks, and educational systems are keeping pace with technological advancement. Main body This critical review examines the rapid emergence of new PET radiopharmaceuticals between 2019 and 2025, analyzing the tension between discovery velocity and the slower process of deep biological validation. We evaluate this phenomenon through four dimensions: (1) biological rationale and mechanistic understanding, (2) clinical validation and comparative effectiveness, (3) standardization of acquisition and interpretation protocols, and (4) integration into clinical practice and education. We explore the limitations of established tracers like [1⁸F]FDG and early-generation prostate-specific membrane antigen (PSMA) ligands that catalyzed innovation, then critically assess the new generation of tracers targeting fibroblast activation protein (FAP), novel PSMA variants, and neurodegeneration biomarkers. A central critique addresses the growing evidence gap: while multiple PSMA tracers have been approved, head-to-head comparative studies remain scarce, and standardization efforts lag behind regulatory approvals. We examine systemic biases favoring novelty over reproducibility in academic incentive structures and discuss the ethical implications of premature clinical adoption. From the perspective of a physician in training, we highlight the practical challenges of navigating a landscape where conference presentations often precede robust clinical evidence. Conclusion The rapid expansion of our PET tracer portfolio reflects remarkable radiopharmaceutical ingenuity. However, translating innovation into meaningful clinical benefit requires a culture of "responsible innovation" that prioritizes fundamental biological understanding, rigorous head-to-head validation studies, harmonized acquisition and interpretation standards, and systematic educational initiatives. Professional societies must strike a balance between encouraging innovation and demanding comparative effectiveness data. Ultimately, the goal is not simply to invent more tracers, but to understand them deeply enough to select the right tracer for the right patient, at the right time, guided by evidence rather than availability.