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The technique is commonly used to determine bone metastatic burden in vivo and also suitable ex vivo to detect even smallest bone micro-metastases in spontaneous metastasis xenograft models. However, it is unclear to which extent ex vivo BLI correlates with alternative methods for metastasis quantification. Here, we compared ex vivo BLI, human DNA-based <jats:italic>Alu<\/jats:italic>-qPCR, and histology for the quantification of bone vs. lung metastases, which are amongst the most common sites of metastasis in prostate cancer (PCa) patients and spontaneous PCa xenograft models. Data from 93 immunodeficient mice were considered, each of which were subcutaneously injected with luciferase\/RGB-labeled human PCa PC-3 cells. The primary tumors were resected at ~\u20090.75\u00a0cm\u00b3 and mice were sacrificed\u2009~\u20093 weeks after surgery and immediately examined by ex vivo BLI. Afterwards, the right lungs and hind limbs with the higher BLI signal (BLI<jats:sup>Hi<\/jats:sup> bone) were processed for histology, whereas the left lung lobes and hind limbs with the lower BLI signal (BLI<jats:sup>Lo<\/jats:sup> bone) were prepared for <jats:italic>Alu<\/jats:italic>-qPCR. Our data demonstrate remarkable differences in the correlation coefficients of the different methods for lung metastasis detection (<jats:italic>r<\/jats:italic>\u2009~\u20090.8) vs. bone metastasis detection (<jats:italic>r<\/jats:italic>\u2009~\u20090.4). However, the BLI values of the BLI<jats:sup>Hi<\/jats:sup> and BLI<jats:sup>Lo<\/jats:sup> bones correlated very strongly (<jats:italic>r<\/jats:italic>\u2009~\u20090.9), indicating that the method per se was reliable under identical limitations; the overall level of metastasis to contralateral bones was astonishingly similar. Instead, the level of lung metastasis only weakly to moderately correlated with the level of bone metastasis formation. Summarized, we observed a considerable discrepancy between ex vivo BLI and histology\/<jats:italic>Alu<\/jats:italic>-qPCR in the quantification of bone metastases, which was not observed in the case of lung metastases. Future studies using ex vivo BLI for bone metastasis quantification should combine multiple methods to accurately determine metastatic load in bone samples.<\/jats:p>","DOI":"10.1007\/s10585-024-10268-4","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T09:02:21Z","timestamp":1707901341000},"page":"103-115","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Comparison of ex vivo bioluminescence imaging, Alu-qPCR and histology for the quantification of spontaneous lung and bone metastases in subcutaneous xenograft mouse models"],"prefix":"10.1007","volume":"41","author":[{"given":"Marie-Therese","family":"Haider","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Freytag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Krause","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Spethmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Gosau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia C.","family":"Beine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Knies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Schr\u00f6der-Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Horn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristoffer","family":"Riecken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Lange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,14]]},"reference":[{"issue":"1","key":"10268_CR1","first-page":"451","volume":"10","author":"BS Chhikara","year":"2022","unstructured":"Chhikara BS, Parang K (2022) Global Cancer statistics 2022: the trends projection analysis. 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