<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" id="d3287239e303">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.
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