Homotypic Targeting of [89Zr]Zr-Oxine Labeled PC3 and 4T1 Cells in Tumor-Bearing Mice

<b>Background/Objectives</b>: Homotypic targeting refers to the ability of cells to preferentially interact with other cells of the same type. An understanding of how cells use homotypic targeting (self-homing) characteristics for tumor-targeting purposes may aid in the effective delivery of radionuclides or other drugs for imaging or therapeutic applications. Additionally, studies investigating the targeting properties of cells from the same lineage may shed light on this interesting mechanism, allowing it to be harnessed for other applications. The objective of this study was to assess the tumor-self targeting potential of PC3 prostate cancer and 4T1 breast cancer cells using a direct cell labeling technique, with a focus on evaluation of cellular labeling efficiency, cell viability, cellular efflux, and in vivo tumor-self targeting capability using both identical and dissimilar tumor models. <b>Methods</b>: [⁸⁹Zr]Zr-oxine was prepared and utilized for the labeling of PC3 and 4T1 cells. Following the assessment of cell labeling efficacy, viability, and efflux, PET/CT imaging and biodistribution studies were conducted with [⁸⁹Zr]Zr-oxine labeled PC3 and 4T1 cells in PC3 and 4T1 tumor-bearing mice models. <b>Results</b>: Both PC3 cells and 4T1 cells were radiolabeled with [⁸⁹Zr]oxine, with PC3 cells illustrating a higher labeling efficiency (86.55 ± 0.38%) than 4T1 cells (46.95 ± 1.47%). Notably, radiolabeled PC3 cells illustrated significant uptake in PC3 tumors (7.54 ± 1.07%ID/gram at 24 h and 6.95 ± 3.56%ID/gram at 48 h) with lower tumor uptake in the 4T1 xenograft model (1.79 ± 0.29%ID/gram at 24 h and 1.42 ± 0.71%ID/gram at 48 h), illustrating the potential of self-targeting. <b>Conclusions</b>: Both PC3 and 4T1 cells followed a similar pattern of biodistribution, with labeled PC3 cells demonstrating lower blood retention and reduced uptake in non-target organs such as lungs and heart. Taken together, these results may indicate that PC3 cells illustrate homotypic targeting, warranting further investigation of this phenomenon.