Tumor Sink Effect in 68 Ga-PSMA-11 PET: Myth or Reality?

The Journal of Nuclear Medicine

article

Andrei Gafita¹  Hui Wang²  Andrew Robertson²  Wesley R. Armstrong¹  Raphael Zaum²  Manuel Weber³  Farid Yagubbayli²  Clemens Kratochwil⁴  Tristan R. Grogan⁵  Kathleen Nguyen¹  Fernando Navarro²  Rouzbeh Esfandiari⁶  Isabel Rauscher²  Bjoern Menze⁷  David Elashoff⁵  Ebrahim S. Delpassand⁶  Ken Herrmann³  Johannes Czernin¹  Michael S. Hofman⁹  Jeremie Calais¹  Wolfgang P. Fendler³  Matthias Eiber² 

[1] Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UCLA;Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich;Department of Nuclear Medicine, University of Duisburg–Essen and German Cancer Consortium–University Hospital Essen;Department of Nuclear Medicine, Heidelberg University Hospital;Department of Medicine Statistics Core, David Geffen School of Medicine, UCLA;Excel Diagnostics and Nuclear Oncology Center;Department of Informatics, Technical University Munich;Department of Quantitative Biomedicine, University of Zurich;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

关键词: PET;    tumor sink effect;    prostate cancer;    PSMA;    Ga-PSMA;    radioligand therapy;   

DOI  :  10.2967/jnumed.121.261906

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

We aimed to systematically determine the impact of tumor burden on 68Ga-prostate-specific membrane antigen-11 (68Ga-PSMA) PET biodistribution by the use of quantitative measurements. Methods: This international multicenter, retrospective analysis included 406 men with prostate cancer who underwent 68Ga-PSMA PET/CT. Of these, 356 had positive findings and were stratified by quintiles into a very low (quintile 1, ≤25 cm3), low (quintile 2, 25–189 cm3), moderate (quintile 3, 189–532 cm3), high (quintile 4, 532–1,355 cm3), or very high (quintile 5, ≥1,355 cm3) 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 68Ga-PSMA PET images, and SUVmean was obtained. Correlations between the SUVmean of normal organs and PSMA-VOL as continuous and categoric variables by quintiles were evaluated. Results: The median PSMA-VOL was 302 cm3 (interquartile range [IQR], 47–1,076 cm3). The median SUVmean 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 SUVmean 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 SUVmean (r = −0.16, P = 0.002). Patients with a very high PSMA-VOL (quintile 5, ≥1,355 cm3) 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 68Ga-PSMA biodistribution in normal organs. Patients with a very high tumor load showed a significantly lower uptake of 68Ga-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.

【 授权许可】

CC BY