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However, specific primary tumour features might impact accuracy of PSMA-PET for PCa detection. We investigated histopathological parameters and immunohistochemical PSMA expression patterns on radical prostatectomy (RPE) specimens and correlated them to the corresponding\n                      <jats:sup>68<\/jats:sup>\n                      Ga-PSMA-11-PET examinations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      RPE specimens of 62 patients with preoperative\n                      <jats:sup>68<\/jats:sup>\n                      Ga-PSMA-11-PET between 2016 and 2018 were analysed. WHO\/ISUP grade groups, growth pattern (expansive vs. infiltrative), tumour area and diameter as well as immunohistochemical PSMA heterogeneity, intensity and negative tumour area (PSMA\n                      <jats:sub>%neg<\/jats:sub>\n                      ) were correlated with spatially corresponding SUV\n                      <jats:sub>max<\/jats:sub>\n                      on\n                      <jats:sup>68<\/jats:sup>\n                      Ga-PSMA-11-PET in a multidisciplinary analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All tumours showed medium to strong membranous (2\u20133\u2009+) and weak to strong cytoplasmic (1\u20133\u2009+) PSMA expression. Heterogeneously expressed PSMA was found in 38 cases (61%). Twenty-five cases (40%) showed at least 5% and up to 80% PSMA\n                      <jats:sub>%neg<\/jats:sub>\n                      . PSMA\n                      <jats:sub>%neg<\/jats:sub>\n                      , infiltrative growth pattern, smaller tumour area and diameter and WHO\/ISUP grade group 2 significantly correlated with lower SUV\n                      <jats:sub>max<\/jats:sub>\n                      values. A ROC curve analysis revealed 20% PSMA\n                      <jats:sub>%neg<\/jats:sub>\n                      as an optimal cutoff with the highest sensitivity and specificity (89% and 86%, AUC 0.923) for a negative PSMA-PET scan. A multiple logistic regression model revealed tumoural PSMA\n                      <jats:sub>%neg<\/jats:sub>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01, OR\u2009=\u20099.629) and growth pattern (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0497, OR\u2009=\u2009306.537) as significant predictors for a negative PSMA-PET scan.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We describe PSMA\n                      <jats:sub>%neg<\/jats:sub>\n                      , infiltrative growth pattern, smaller tumour size and WHO\/ISUP grade group 2 as parameters associated with a lower\n                      <jats:sup>68<\/jats:sup>\n                      Ga-PSMA-11 uptake in prostate cancer. These findings can serve as fundament for future biopsy-based biomarker development to enable an individualized, tumour-adapted imaging approach.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-021-05501-1","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T23:34:09Z","timestamp":1628811249000},"page":"4042-4053","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["What\u2019s behind 68Ga-PSMA-11 uptake in primary prostate cancer PET? 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Hoffmann-La Roche AG.JHR, DAF, UJM, RL, AKR, HM and DE declare no conflict of interest.The Department of Nuclear Medicine holds an institutional Research Contract with GE Healthcare.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}