Biodistribution, dosimetry, and preliminary imaging of the novel Nectin-4-targeting PET tracer [⁶⁸Ga]Ga-FZ-NR-1 in humans.

[BACKGROUND] Nectin-4 is a promising theranostic target for cancers treatment due to its high abundance/expression in different cancer entities such as bladder cancer, breast cancer, and pancreatic cancer This study evaluated the biodistribution and radiation dosimetry of [⁶⁸Ga]Ga-DOTA-Sar¹⁰-Nectin-4 ([⁶⁸Ga]Ga-FZ-NR-1), a novel Nectin-4-targeting PET tracer developed by our team, to assess its safety and support its clinical translation. Eight patients with pathologically confirmed malignancies (breast cancer, pancreatic cancer, or bladder cancer) underwent whole-body (WB) PET/CT scans at 10, 40, and 180 min after the injection of [⁶⁸Ga]Ga-FZ-NR-1. The images were reconstructed using the Ordered Subset Expectation Maximization (OSEM) algorithm with TOF and PSF technology. The brain, salivary, heart, lungs, stomach, spleen, liver, gallbladder, pancreas, kidneys, colon, and prostate in males or uterus in females as target organs were semi-automatically segmented on PET/CT images using the Hermes Internal Radiation Dosimetry (HIRD) software toolkit. Time-activity curves (TACs) were obtained for these organs based on measured activity concentrations. The time-integrated activity coefficients (TIACs) of these target organs were calculated by integrating the TACs. Organ-specific absorbed doses and the total body effective dose were estimated using IDAC-Dose 2.1 software. Meanwhile, bladder dosimetry employed a standard voiding model.

[RESULTS] [⁶⁸Ga]Ga-FZ-NR-1 was cleared rapidly, primarily via the urinary system. The highest organ absorbed doses per injected activity unit were observed in the kidneys (2.24 × 10⁻¹ mGy/MBq) and bladder wall (1.24 × 10⁻¹ mGy/MBq). Other notable organs were the salivary glands, with an absorbed dose of approximately 2.54 × 10⁻² mGy/MBq. The estimated total body effective dose per injected activity unit was approximately 2.00 × 10⁻² mSv/MBq. Preliminary clinical imaging showed high tracer uptake in breast, pancreatic, and bladder cancer lesions, highlighting its promising diagnostic potential for detecting Nectin-4-expressing tumors.

[CONCLUSION] This human dosimetry assessment of [⁶⁸Ga]Ga-FZ-NR-1 showed a total body effective dose of approximately 2.00 × 10⁻² mSv/MBq, similar to other Gallium-labeled tracers. Organ absorbed doses were well within the accepted limits, suggesting a favorable radiation risk profile for clinical application as a PET imaging agent targeting Nectin-4. Initial clinical imaging results demonstrates that [⁶⁸Ga]Ga-FZ-NR-1 provides clear visualization of both primary tumors and metastases with high Nectin-4 expression levels.