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However, the molecular and cellular factors driving tumor-neural stroma interactions remain unclear. Here, we developed a co-culture model of metastatic melanoma by combining metastatic melanoma cells with dissociated human iPSC-derived cerebral organoids, consisting of neurons and astrocytes, in a microfluidic device. We cultured these astrocytes and neurons in a 3D hydrogel that contained a domain with metastatic melanoma cells. This approach generated a spatially organized co-culture system with no physical boundary between the tumor and stromal compartments. Then, we leveraged several imaging modalities to study tumor-stroma interactions and changes in the microenvironment. Using non-destructive, luminescence-based methods, we spatially resolved changes in cell viability, metabolite concentration, and other biochemical parameters. We also used luminescence to analyze the effect of radionuclides on tumor cell viability and used PET imaging to monitor their diffusion across the system.<\/jats:p>","DOI":"10.1088\/1758-5090\/ade1fb","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T18:50:31Z","timestamp":1749235831000},"page":"035021","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Non-destructive luminescence and PET imaging to monitor tissue microenvironment in microphysiological systems during brain metastasis using dissociated cerebral organoids"],"prefix":"10.1088","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2406-8830","authenticated-orcid":false,"given":"Catherine","family":"Reed-McBain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2118-3444","authenticated-orcid":true,"given":"Rithvik V","family":"Turaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9329-0068","authenticated-orcid":true,"given":"Seth R T","family":"Zima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5069-0945","authenticated-orcid":true,"given":"Janmesh","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson Weber Faletti","family":"Cunha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3045-5607","authenticated-orcid":true,"given":"Jason","family":"Mixdorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8384-6102","authenticated-orcid":true,"given":"Lauren E","family":"Wehner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan W","family":"Engle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinier","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stevens K","family":"Rehen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena L","family":"Borges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9414-1845","authenticated-orcid":true,"given":"Jose M","family":"Ayuso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"bfade1fbbib1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13046-018-0674-x","article-title":"Role of the nervous system in cancer metastasis","volume":"37","author":"Kuol","year":"2018","journal-title":"J. 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