Multimodal SPECT-Based Molecular Probes for Tumor Imaging and Theranostics

Single-photon emission computed tomography (SPECT) delivers exceptional molecular sensitivity and quantitative whole-body imaging, yet its intrinsically limited spatial resolution and lack of anatomical detail constrain comprehensive tumor evaluation. Recent advances in radiochemistry, molecular design, and nanotechnology have promoted the emergence of multimodal and multifunctional SPECT probes that integrate nuclear imaging with magnetic, optical, and photoacoustic modalities, while increasingly incorporating therapeutic components. These hybrid systems enable precise tumor localization, real-time intraoperative guidance, and longitudinal tracking of therapeutic responses, effectively merging diagnostic and treatment capabilities within a single molecular framework. In this review, we highlight key innovations in probe designing, elucidate structure-property relationship that govern in vivo performance, and critically examine the chemical, biological, and translational barriers that must be addressed for clinical implementation. By outlining strategic opportunities and design principles, this work aims to guide the development of next-generation SPECT-based multimodal and theranostic platforms for precision oncology.