Tumor Sink Effect in <sup>68</sup>Ga-PSMA-11 PET: Myth or Reality?
Andrei Gafita, Hui Wang, Andrew Robertson, Wesley R. Armstrong, Raphael Zaum, Manuel Weber, Farid Yagubbayli, Clemens Kratochwil, Tristan Grogan, Kathleen Nguyen, Fernando Navarro, Rouzbeh Esfandiari, Isabel Rauscher, Bjoern Menze, David Elashoff, Ebrahim S. Delpassand, Ken Herrmann, Johannes Czernin, Michael S. Hofman, Jérémie Calais, Wolfgang P. Fendler, Matthias Eiber
Abstract
<b>Background:</b> We aimed to systematically determine the impact of tumor burden on the <sup>68</sup>Ga-prostate-specific membrane antigen-11 (<sup>68</sup>Ga-PSMA) PET biodistribution by the use of quantitative measurements. <b>Methods:</b> This international multicenter retrospective analysis included 406 men with prostate cancer who received <sup>68</sup>Ga-PSMA PET/CT. Of these, 356 had positive findings and were stratified by quintiles into very low (Q1, ≤25 ml), low (Q2, 25-189 ml), moderate (Q3, 189-532 ml), high (Q4, 532-1355 ml) and very high (Q5, ≥1355 ml) total PSMA-positive tumor volume (PSMA-VOL). PSMA-VOL was obtained by semi-automatic segmentation of total tumor lesions using qPSMA software. Fifty prostate cancer patients with no PSMA-positive lesions (negative scan) served as control group. Normal organs, which included salivary glands, liver, spleen and kidneys, were semi-automatically segmented using <sup>68</sup>Ga-PSMA PET images and average SUV (SUVmean) was obtained. Correlations of PSMA-VOL as continuous and as categorical variable by quintiles with SUVmean of normal organ were evaluated. <b>Results:</b> The median PSMA-VOL was 302 ml (interquartile range [IQR], 47-1076). The median (IQR) SUVmean of salivary glands, kidneys, liver and spleen was 10.0 (7.7-11.8), 26.0 (20.0-33.4), 3.7 (3.0-4.7) and 5.3 (4.0-7.2), respectively. PSMA-VOL showed a moderate negative correlation with SUVmean of 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 spleen SUVmean (r=-0.16, <i>P</i> = 0.002). Patients with very high PSMA-VOL (Q5, ≥1355 ml) had a significant lower PSMA uptake of salivary glands, kidneys, liver and spleen compared to the control group with an average difference of -38.1%, -40.0%, -43.2% and -34.9%, respectively (p<0.001). <b>Conclusion:</b> Tumor sequestration affects <sup>68</sup>Ga-PSMA biodistribution in normal organs. Patients with very high tumor load showed a significant lower uptake of <sup>68</sup>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.