Multimodal imaging probes combine different imaging modalities to enhance diagnostic capabilities. The challenge lies in balancing sensitivity and resolution, but combining modalities has become popular, exemplified by the first commercial PET/CT instrument in 2001. PET/MRI has since emerged, though development was slower due to technical challenges. Recent research has surged in multimodal contrast agents, enabling simultaneous tracking of molecular targets and clearer delineation of biochemical markers. Dual-function probes, like PET/MRI, use high-sensitivity PET for whole-body screening, reducing MRI scan time. However, probe design sometimes precedes clear applications, leading to probes with unique properties yet no clear medical use. Despite this, multimodal functionality has driven innovation in chemical synthesis, notably in nanotechnology. Lipid-based carriers, such as liposomes, have been used to encapsulate or attach contrast agents. Encapsulation in the aqueous core allows multiple agents to be combined, improving plasma half-life and circulation time. However, encapsulation efficiency is low, and agents may leak. Liposomes can also be modified to enhance tissue penetration, such as using cationic liposomes for cell uptake. Perfluorocarbons, detectable by ultrasound and MRI, have been used in emulsions and nanoemulsions for multimodal imaging. These materials are biologically inert and can be used as blood substitutes or for lung imaging. Lipoproteins, like LDL and HDL, have also been used as carriers for multimodal probes. LDL can be modified with dyes and targeting moieties, while HDL-like particles have been engineered with gold, iron oxide, or quantum dot nanoparticles for CT, MRI, and fluorescence imaging. These particles can target specific receptors and enhance contrast in imaging. Nanoparticle designs, particularly quantum dots, have shown promise in multimodal imaging. Quantum dots can be conjugated with MRI or PET agents through surface chemistry or core/shell structures. These nanoparticles offer high sensitivity and can be functionalized with multiple agents. Challenges include ensuring stability and optimizing loading for effective imaging. Recent studies have demonstrated the potential of quantum dots for PET, MRI, and optical imaging, though further research is needed to improve contrast in animal models. Overall, multimodal imaging probes continue to advance, offering new possibilities for diagnostic and therapeutic applications.Multimodal imaging probes combine different imaging modalities to enhance diagnostic capabilities. The challenge lies in balancing sensitivity and resolution, but combining modalities has become popular, exemplified by the first commercial PET/CT instrument in 2001. PET/MRI has since emerged, though development was slower due to technical challenges. Recent research has surged in multimodal contrast agents, enabling simultaneous tracking of molecular targets and clearer delineation of biochemical markers. Dual-function probes, like PET/MRI, use high-sensitivity PET for whole-body screening, reducing MRI scan time. However, probe design sometimes precedes clear applications, leading to probes with unique properties yet no clear medical use. Despite this, multimodal functionality has driven innovation in chemical synthesis, notably in nanotechnology. Lipid-based carriers, such as liposomes, have been used to encapsulate or attach contrast agents. Encapsulation in the aqueous core allows multiple agents to be combined, improving plasma half-life and circulation time. However, encapsulation efficiency is low, and agents may leak. Liposomes can also be modified to enhance tissue penetration, such as using cationic liposomes for cell uptake. Perfluorocarbons, detectable by ultrasound and MRI, have been used in emulsions and nanoemulsions for multimodal imaging. These materials are biologically inert and can be used as blood substitutes or for lung imaging. Lipoproteins, like LDL and HDL, have also been used as carriers for multimodal probes. LDL can be modified with dyes and targeting moieties, while HDL-like particles have been engineered with gold, iron oxide, or quantum dot nanoparticles for CT, MRI, and fluorescence imaging. These particles can target specific receptors and enhance contrast in imaging. Nanoparticle designs, particularly quantum dots, have shown promise in multimodal imaging. Quantum dots can be conjugated with MRI or PET agents through surface chemistry or core/shell structures. These nanoparticles offer high sensitivity and can be functionalized with multiple agents. Challenges include ensuring stability and optimizing loading for effective imaging. Recent studies have demonstrated the potential of quantum dots for PET, MRI, and optical imaging, though further research is needed to improve contrast in animal models. Overall, multimodal imaging probes continue to advance, offering new possibilities for diagnostic and therapeutic applications.