The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... · 2025
Tumor sink effect in PSMA-targeted theranostics: intra-patient evaluation of a cohort receiving 225Ac/177Lu-PSMA tandem radioligand therapy.
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Burgard Caroline, Muenzenberg Marie D, Blickle Arne, Bartholomä Mark, Maus Stephan, Petto Sven, Schaefer-Schuler Andrea, Ezziddin Samer, Rosar Florian
Аннотация
BACKGROUND: This study aims to further strengthen the evidence of tumor sink effect (TSE) and to confirm this phenomenon in patients undergoing 225Ac/177Lu-PSMA tandem radioligand therapy.
METHODS: The study included a total of N.=31 mCRPC patients who undergone two cycles of [177Lu]Lu-PSMA-617 RLT, with at least one cycle being augmented by [225Ac]Ac-PSMA-617. For pre- and post-therapeutic [68Ga]Ga-PSMA-11 PET/CT scans the standardized uptake value (SUV<inf>mean</inf>) of the liver, kidneys, parotid glands, and spleen as well as the total lesion PSMA (TLP) were assessed and compared.
RESULTS: The mean TLP value decreased by 31.32% after two cycles of PSMA-RLT. Overall, significant increases in SUV<inf>mean</inf> were noted in the spleen (P=0.002) and liver (P=0.009). Especially, responders exhibited significant SUV<inf>mean</inf> increases in the spleen (P<0.001, baseline mean: 5.35 vs. follow-up mean: 7.28), liver (P=0.001, 4.21 vs. 5.00), and kidney (P=0.003, 17.30 vs. 20.43). Correlation analysis revealed significant relationships between change in TLP and change in SUV<inf>mean</inf> in the parotid gland (r=0.408, P=0.023) and spleen (r=0.410, P=0.022). The strength of TSE varied with tumor size, with an increase in tumor burden leading to a stronger TSE.
CONCLUSIONS: This analysis demonstrates the presence of the TSE in mCRPC patients undergoing the innovative 225Ac/177Lu-PSMA tandem radioligand therapy concept. TSE may hold significant clinical implications and may play a role towards more individualized RLT.
METHODS: The study included a total of N.=31 mCRPC patients who undergone two cycles of [177Lu]Lu-PSMA-617 RLT, with at least one cycle being augmented by [225Ac]Ac-PSMA-617. For pre- and post-therapeutic [68Ga]Ga-PSMA-11 PET/CT scans the standardized uptake value (SUV<inf>mean</inf>) of the liver, kidneys, parotid glands, and spleen as well as the total lesion PSMA (TLP) were assessed and compared.
RESULTS: The mean TLP value decreased by 31.32% after two cycles of PSMA-RLT. Overall, significant increases in SUV<inf>mean</inf> were noted in the spleen (P=0.002) and liver (P=0.009). Especially, responders exhibited significant SUV<inf>mean</inf> increases in the spleen (P<0.001, baseline mean: 5.35 vs. follow-up mean: 7.28), liver (P=0.001, 4.21 vs. 5.00), and kidney (P=0.003, 17.30 vs. 20.43). Correlation analysis revealed significant relationships between change in TLP and change in SUV<inf>mean</inf> in the parotid gland (r=0.408, P=0.023) and spleen (r=0.410, P=0.022). The strength of TSE varied with tumor size, with an increase in tumor burden leading to a stronger TSE.
CONCLUSIONS: This analysis demonstrates the presence of the TSE in mCRPC patients undergoing the innovative 225Ac/177Lu-PSMA tandem radioligand therapy concept. TSE may hold significant clinical implications and may play a role towards more individualized RLT.