Biokinetics and Dosimetry of [177Lu]Lu-Pentixather

The chemokine receptor CXCR4, which is overexpressed in many solid and hematologic malignancies, can be targeted for radiopeptide therapy via the antagonist Pentixather®. Biokinetics and dosimetry of ¹⁷⁷Lu-Pentixather and ⁹⁰Y-Pentixather were analyzed. Methods: This retrospective study is a standardized reevaluation of data collected for treatment planning. Nineteen patients with complete sets of planar whole-body scans over at least four days and a single SPECT/CT after 200 MBq ¹⁷⁷Lu-Pentixather were included. Kinetics were measured in the whole body, in tissues with activity retention, and in 10 individuals in the blood. Time-integrated activity coefficients and tissue absorbed doses were derived. Results: Increased uptake of Pentixather was observed in kidneys, liver, spleen, and bone marrow, inducing median (minimum-maximum) absorbed doses of 0.91 (0.38-3.47), 0.71 (0.39-1.17), 0.58 (0.34-2.26), and 0.47 (0.14-2.33) Gy per GBq ¹⁷⁷Lu-Pentixather and 3.75 (1.48-12.2), 1.61 (1.14-2.97), 1.66 (0.97-6.69), and 1.06 (0.27-4.45) Gy per GBq ⁹⁰Y-Pentixather, respectively. In most tissues, activity increased during the first day after the administration of ¹⁷⁷Lu-Pentixather and afterwards decayed with mean effective half-lives of 41 ± 10 (range: 24-64) hours in kidneys and median half-lives of 109, 86, and 92 hours in liver, spleen, and bone marrow, respectively. Maximum uptake per kidney was 2.2% ± 1.0% (range: 0.6%-5.1%). In organs showing no specific uptake, absorbed doses exceeding 0.3 Gy per GBq ⁹⁰Y-Pentixather are estimated for the urinary bladder and for tissues adjacent to accumulating organs such as the adrenal glands, bone surface, and gallbladder. Dose estimates for tumors and extramedullary lesions ranged from 1.5 to 18.2 Gy per GBq ⁹⁰Y-Pentixather. Conclusion: In patients with hematologic neoplasms, absorbed doses calculated for bone marrow and extramedullary lesions are sufficient to be effective as an adjunct to high-dose chemotherapies prior to stem cell transplantation.