PMID- 34049987 OWN - NLM STAT- MEDLINE DCOM- 20220429 LR - 20230613 IS - 1535-5667 (Electronic) IS - 0161-5505 (Print) IS - 0161-5505 (Linking) VI - 63 IP - 2 DP - 2022 Feb TI - Tumor Sink Effect in (68)Ga-PSMA-11 PET: Myth or Reality? PG - 226-232 LID - 10.2967/jnumed.121.261906 [doi] AB - We aimed to systematically determine the impact of tumor burden on (68)Ga-prostate-specific membrane antigen-11 ((68)Ga-PSMA) PET biodistribution by the use of quantitative measurements. Methods: This international multicenter, retrospective analysis included 406 men with prostate cancer who underwent (68)Ga-PSMA PET/CT. Of these, 356 had positive findings and were stratified by quintiles into a very low (quintile 1, /=1,355 cm(3)) total PSMA-positive tumor volume (PSMA-VOL). PSMA-VOL was obtained by semiautomatic segmentation of total tumor lesions using qPSMA software. Fifty prostate cancer patients with no PSMA-positive lesions (negative scan) served as a control group. Normal organs, which included salivary glands, liver, spleen, and kidneys, were semiautomatically segmented using (68)Ga-PSMA PET images, and SUV(mean) was obtained. Correlations between the SUV(mean) of normal organs and PSMA-VOL as continuous and categoric variables by quintiles were evaluated. Results: The median PSMA-VOL was 302 cm(3) (interquartile range [IQR], 47-1,076 cm(3)). The median SUV(mean) of salivary glands, kidneys, liver, and spleen was 10.0 (IQR, 7.7-11.8), 26.0 (IQR, 20.0-33.4), 3.7 (IQR, 3.0-4.7), and 5.3 (IQR, 4.0-7.2), respectively. PSMA-VOL showed a moderate negative correlation with the SUV(mean) of the salivary glands (r = -0.44, P < 0.001), kidneys (r = -0.34, P < 0.001), and liver (r = -0.30, P < 0.001) and a weak negative correlation with the spleen SUV(mean) (r = -0.16, P = 0.002). Patients with a very high PSMA-VOL (quintile 5, >/=1,355 cm(3)) had a significantly lower PSMA uptake in the salivary glands, kidneys, liver, and spleen than did the control group, with an average difference of -38.1%, -40.0%, -43.2%, and -34.9%, respectively (P < 0.001). Conclusion: Tumor sequestration affects (68)Ga-PSMA biodistribution in normal organs. Patients with a very high tumor load showed a significantly lower uptake of (68)Ga-PSMA in normal organs, confirming a tumor sink effect. As similar effects might occur with PSMA-targeted radioligand therapy, these patients might benefit from increased therapeutic activity without exceeding the radiation dose limit for organs at risk. CI - (c) 2022 by the Society of Nuclear Medicine and Molecular Imaging. FAU - Gafita, Andrei AU - Gafita A AD - Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California; agafita@mednet.ucla.edu. AD - Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany. FAU - Wang, Hui AU - Wang H AD - Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany. FAU - Robertson, Andrew AU - Robertson A AD - Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany. FAU - Armstrong, Wesley R AU - Armstrong WR AD - Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California. FAU - Zaum, Raphael AU - Zaum R AD - Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany. FAU - Weber, Manuel AU - Weber M AD - Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium-University Hospital Essen, Essen, Germany. FAU - Yagubbayli, Farid AU - Yagubbayli F AD - Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany. FAU - Kratochwil, Clemens AU - Kratochwil C AD - Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany. FAU - Grogan, Tristan R AU - Grogan TR AD - Department of Medicine Statistics Core, David Geffen School of Medicine, UCLA, Los Angeles, California. FAU - Nguyen, Kathleen AU - Nguyen K AD - Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California. FAU - Navarro, Fernando AU - Navarro F AD - Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany. AD - Department of Informatics, Technical University Munich, Munich, Germany. FAU - Esfandiari, Rouzbeh AU - Esfandiari R AD - Excel Diagnostics and Nuclear Oncology Center, Houston, Texas. FAU - Rauscher, Isabel AU - Rauscher I AD - Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany. FAU - Menze, Bjoern AU - Menze B AD - Department of Informatics, Technical University Munich, Munich, Germany. AD - Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland; and. FAU - Elashoff, David AU - Elashoff D AD - Department of Medicine Statistics Core, David Geffen School of Medicine, UCLA, Los Angeles, California. FAU - Delpassand, Ebrahim S AU - Delpassand ES AD - Excel Diagnostics and Nuclear Oncology Center, Houston, Texas. FAU - Herrmann, Ken AU - Herrmann K AD - Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium-University Hospital Essen, Essen, Germany. FAU - Czernin, Johannes AU - Czernin J AD - Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California. FAU - Hofman, Michael S AU - Hofman MS AD - Prostate Cancer Theranostics and Imaging Centre of Excellence, Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia. FAU - Calais, Jeremie AU - Calais J AD - Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, California. FAU - Fendler, Wolfgang P AU - Fendler WP AD - Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium-University Hospital Essen, Essen, Germany. FAU - Eiber, Matthias AU - Eiber M AD - Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany. LA - eng GR - P30 CA016042/CA/NCI NIH HHS/United States GR - P50 CA211015/CA/NCI NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20210528 PL - United States TA - J Nucl Med JT - Journal of nuclear medicine : official publication, Society of Nuclear Medicine JID - 0217410 RN - 0 (Gallium Isotopes) RN - 0 (Gallium Radioisotopes) RN - 0 (gallium 68 PSMA-11) RN - 9G34HU7RV0 (Edetic Acid) SB - IM CIN - J Nucl Med. 2022 Jul;63(7):1124-1125. PMID: 35027370 CIN - J Nucl Med. 2022 Jul;63(7):1124. PMID: 35483966 MH - Edetic Acid MH - Gallium Isotopes MH - *Gallium Radioisotopes MH - Humans MH - Male MH - Positron Emission Tomography Computed Tomography/methods MH - *Prostatic Neoplasms/diagnostic imaging/pathology MH - Retrospective Studies MH - Tissue Distribution PMC - PMC8805781 OTO - NOTNLM OT - Ga-PSMA OT - PET OT - PSMA OT - prostate cancer OT - radioligand therapy OT - tumor sink effect EDAT- 2021/05/30 06:00 MHDA- 2022/04/30 06:00 PMCR- 2022/02/01 CRDT- 2021/05/29 05:41 PHST- 2021/01/04 00:00 [received] PHST- 2021/05/04 00:00 [revised] PHST- 2021/05/30 06:00 [pubmed] PHST- 2022/04/30 06:00 [medline] PHST- 2021/05/29 05:41 [entrez] PHST- 2022/02/01 00:00 [pmc-release] AID - jnumed.121.261906 [pii] AID - 261906 [pii] AID - 10.2967/jnumed.121.261906 [doi] PST - ppublish SO - J Nucl Med. 2022 Feb;63(2):226-232. doi: 10.2967/jnumed.121.261906. Epub 2021 May 28.