Iodine-124 Based Dual Positron Emission Tomography and Fluorescent Labeling Reagents for In Vivo Cell Tracking

Abstract

Understanding the in vivo behavior of experimental therapeutic cells is fundamental to their successful development and clinical translation. Iodine-124 has the longest half-life (4.2 days) among the clinically used positron emitters. Consequently, this isotope offers the longest possible tracking time for directly labeled cells using positron emission tomography (PET). Herein, we have radiosynthesized and evaluated two iodine-124/fluorescein-based dual PET and fluorescent labeling reagents, namely 124I-FIT-Mal and 124I-FIT-(PhS)2Mal for cell surface thiol bioconjugation. 124I-FIT-(PhS)2Mal labeled cells significantly more effectively than 124I-FIT-Mal. It conjugated to various cell lines in 22%–62% labeling efficiencies with prolonged iodine-124 retention. 124I-FIT-(PhS)2Mal mainly conjugated on the cell membrane, which was confirmed by high-resolution fluorescence imaging. The migration of 124I-FIT-(PhS)2Mal labeled Jurkat cells was visualized in NSG mice with excellent target-to-background contrast using PET/CT over 7 days. These data demonstrate that 124I-FIT-(PhS)2Mal can dynamically track cell migration in vivo using PET/CT over a clinically relevant time frame.

Optimisation of the Synthesis and Cell Labelling Conditions for [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS: a Direct In Vitro Comparison in Cell Types with Distinct Therapeutic Applications

“…There is a need for sensitive tools that can be used to better understand the in vivo migration and behaviour of transplanted cells. Long-term cell tracking with PET is gaining more interest and can serve as an efficient and important tool in the development of cell-based therapies [ 7 , 9 , 21 , 30 ].…”

“…Compared to SPECT, PET imaging provides higher spatial resolution, better sensitivity and quantification ability [ 18 ]. PET tracers that have been used for cell labelling include [ 18 F]FDG [ 17 , 19 ], [ 64 Cu]Cu-PTSM, [ 124 I]FIAU [ 20 ], [ 124 I]FIT-Mal and [ 124 I]FIT-(PhS)2-Mal [ 21 ]. Unfortunately, these tracers have either too short half-lives, which are not suitable for long-term cell tracking, and/or low cellular retention, causing a high radioactive dose to the blood, bone marrow and excretion organs, and a low target-to-background ratio.…”

Efficiency of 124I radioisotope production from natural and enriched tellurium dioxide using 124Te(p,xn)124I reaction

“…However, the clinical applications of this radioisotope are limited owing to its very high production cost and lack of widespread availability [ 47 ]. The interest in 124 I applications is expected to grow, as it can be attached to the cell surface and used in cell labelling, opening new possibilities in the studies of human metabolism [ 4 , 48 ]. Only about 23% of its disintegration is via positron emission of relatively high energy [ 6 ].…”

The chemical tool-kit for molecular imaging with radionuclides in the age of targeted and immune therapy

“…A simplified, good manufacturing practice (GMP)-compatible kit-based method of producing the 89 Zr-oxine complex has been reported recently, [60] greatly enhancing the opportunity for wider use in clinical trials of cell-based therapy. An alternative approach to cell labelling is by conjugation of DFO-based zirconium-89 chelates [61] or iodine-124-prosthetic groups [62] (Fig. 9 ], have also been used to label liposomal drug formulations for PET imaging of their biodistribution [63].…”