[⁸⁹Zr]-PSMA Df offers a prolonged time frame for prostate cancer imaging: A comparison with short-lived PSMA tracers.

Objectives: The detection of prostate carcinoma lesions by means of PSMA-PET is usually realized today within a few hours after injection of radiotracers such as [⁶⁸Ga]-PSMA 11 or [¹⁸F]-JK-PSMA 7. An optimal contrast cannot possibly be achieved within such a short biodistribution period, We therefore introduce a new PSMA-binding compound that exploits the longer physical half-life (78h) of ⁸⁹Zr: [⁸⁹Zr]-PSMA Df.

Methods: The N-sucDF-Fe moiety functionalizing the molecule for labeling with ⁸⁹Zr was attached to a precursor provided by ABX GmbH (Radeberg). The [⁸⁹Zr]-PSMA Df was characterized in vitro by calculation of the corresponding K_d value, the cellular uptake and the internalization in LNCaP cells. Its biodistribution in vivo was studied with LNCaP prostate tumor xenografts in mice, and PET-imaging experiments were conducted on a Focus 220 micro PET scanner. For comparison, analog experiments and compound characterization were carried out with [⁶⁸Ga]-PSMA 11 and [¹⁸F]-JK-PSMA 7.

Results: The labeling of [⁸⁹Zr]-PSMA Df was performed to a radiochemical purity ≥99.9%. It showed very high stability in PBS and human serum for up to 7 days at 37 ^oC. At 2 h, all radiotracers showed a comparable tumor uptake of approximately 20% ID/g. [⁸⁹Zr]-PSMA Df allowed the acquisition of small animal PET-images with demarcated tumor after 24 h and 52 h p.i., showing that over time the compound remains in the tumor with very low activity in background tissue except for the kidneys. The analysis of the PET-images also revealed an increase in tumor-to-background ratio over time.

Conclusions: This study demonstrates that the tumor uptake and biodistribution of [⁸⁹Zr]-PSMA Df in normal tissues is comparable to that of [⁶⁸Ga]-PSMA 11 and [¹⁸F]-JK-PSMA 7, but remains in the tumor for at least 52 h p.i. with increasing tumor-to-background ratio. This, together with the long half-life of the [⁸⁹Zr]-label allows late PET-acquisition with improved lesion detection. Tumors with lower PSMA expression are thus more likely to be detected than with existing ¹⁸F- or ⁶⁸Ga labeled PSMA targeted imaging agents.

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