A major barrier to clinical translation of cellular therapies is the limited understanding of their fate and distribution post-administration. The literature documents multiple approaches to track cells using labels and various modalities such as magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT) and scintigraphy, however, the terminology is inconsistent and difficult to make cross-study comparisons. To address this, the Health & Environmental Science Institute’s Cell Therapy – Tracking, Circulation and Safety (HESI CT/TRACS) committee established the Data Portal for Imaging Cell Therapies (DPICT) database focused on collating the literature relating to cell fate tracking. Initial attempts to populate the database by academic, regulatory, and industry experts identified 61 articles. To build on these efforts and ensure a comprehensive collection, we performed a systematic review to collate all the methods of tracking cells that have been used in clinical trials and human whole organ studies where cells are administered in vivo as a therapeutic. 

In April 2025, Medline Ovid, Pubmed and Scopus databases were systematically searched for papers published in English, post-2001 with the following key word sequence structure: (imaging modality) AND (cell label) AND (cell type) AND (humans OR human study OR human studies OR clinical study OR clinical studies OR clinically OR patient* OR perfusion). Initial DPICT database papers were used as a positive control. Data extracted included; cell type, disease indication, imaging technology used for cell tracking, imaging probe, reporter gene, observation times, region and research funding source.

A total of 78 articles met the inclusion criteria, with most studies tracking PBMCs, specifically DC-vaccines (16.7%), employing scintigraphy (34%) and enrolled patients with a cancer diagnosis (30.8%) including melanoma, glioblastoma and breast cancer. Common themes amongst the articles included a need for a contrast agents with long half-life in longitudinal studies, imaging modalities with high resolution/specificity and cellular therapies that migrate to the target site to work effectively.

The frequent use of PBMCs like DCs reflects their accessibility and established role in clinical trials, particularly in cancer immunotherapy. However, a decline in biodistribution publications after 2015 may indicate growing recognition of limitations in imaging modalities - especially the short maximum tracking durations, with most studies reporting observation periods of ≤1 week. By systematically mapping these trends, this review supports the population of the DPICT database with up-to-date cell tracking articles that have been cultivated to benefit the cell-therapy community. This will guide future research by identifying gaps in the field and limitations of current imaging modalities, contrast agents and cellular therapeutic action.