Direct Cell Radiolabeling for in Vivo Cell Tracking with PET and SPECT Imaging

Abstract

The arrival of cell-based therapies is a revolution in medicine. However, its safe clinical application in a rational manner depends on reliable, clinically applicable methods for determining the fate and trafficking of therapeutic cells in vivo using medical imaging techniquesknown as in vivo cell tracking. Radionuclide imaging using single photon emission computed tomography (SPECT) or positron emission tomography (PET) has several advantages over other imaging modalities for cell tracking because of its high sensitivity (requiring low amounts of probe per cell for imaging) and whole-body quantitative imaging capability using clinically available scanners. For cell tracking with radionuclides, ex vivo direct cell radiolabeling, that is, radiolabeling cells before their administration, is the simplest and most robust method, allowing labeling of any cell type without the need for genetic modification. This Review covers the development and application of direct cell radiolabeling probes utilizing a variety of chemical approaches: organic and inorganic/coordination (radio)chemistry, nanomaterials, and biochemistry. We describe the key early developments and the most recent advances in the field, identifying advantages and disadvantages of the different approaches and informing future development and choice of methods for clinical and preclinical application.

Diagnostic and Therapeutic Radiopharmaceuticals

“…46 F. Application of PET/SPECT imaging modality to study intestinal absorption and body distribution of orally administered radiolabeled endogenous compounds 47 and in vivo cell tracking. 48 The upcoming joint Virtual Special Issue on "Diagnostic and Therapeutic Radiopharmaceuticals" aims to bring together contributions from radiopharmaceutical science integrated with medicinal chemistry and translational preclinical or even clinical studies. We give priority to studies on the design, synthesis, and biological evaluation of novel diagnostic and therapeutic radiopharmaceuticals and multimodal probes that have translational potential in a broad range of biomedical disciplines.…”

Illuminating spatial pharmacology with in situ drug imaging

“…Although it retains spatial information, positron emission tomography generally lacks sufficient resolution to resolve cell type identities. 3 Fluorescence‐based imaging has been widely used with antibodies or messenger ribonucleic acid (mRNA) probes to visualize endogenous biomolecules, but such tags are too bulky to fit small molecule drugs. To circumvent these barriers, we turned to copper(I)‐catalyzed azide‐alkyne cycloaddition (CuAAC) click reaction.…”

“…Conventional bulk tissue analysis loses spatial and cellular information. Although it retains spatial information, positron emission tomography generally lacks sufficient resolution to resolve cell type identities 3 . Fluorescence‐based imaging has been widely used with antibodies or messenger ribonucleic acid (mRNA) probes to visualize endogenous biomolecules, but such tags are too bulky to fit small molecule drugs.…”

Diagnostic and Therapeutic Radiopharmaceuticals

“…46 F. Application of PET/SPECT imaging modality to study intestinal absorption and body distribution of orally administered radiolabeled endogenous compounds 47 and for in vivo cell tracking. 48 The upcoming joint Virtual Special Issue on "Diagnostic and Therapeutic Radiopharmaceuticals" aims to bring together contributions from radiopharmaceutical science integrated with medicinal chemistry and translational preclinical or even clinical studies. We give priority to studies on the design, synthesis, and biological evaluation of novel diagnostic and therapeutic radiopharmaceuticals and multimodal probes that have translational potential in a broad range of biomedical disciplines.…”

“… Application of PET/SPECT imaging modality to study intestinal absorption and body distribution of orally administered radiolabeled endogenous compounds and for in vivo cell tracking. …”