{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T12:11:05Z","timestamp":1791634265389,"version":"4.3.4"},"reference-count":167,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"NIH","doi-asserted-by":"publisher","award":["R15CA268200"],"award-info":[{"award-number":["R15CA268200"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>5-Aminolevulinic acid (ALA) is a naturally occurring amino acid synthesized in all nucleated mammalian cells. As a porphyrin precursor, ALA is metabolized in the heme biosynthetic pathway to produce protoporphyrin IX (PpIX), a fluorophore and photosensitizing agent. ALA administered exogenously bypasses the rate-limit step in the pathway, resulting in PpIX accumulation in tumor tissues. Such tumor-selective PpIX disposition following ALA administration has been exploited for tumor fluorescence diagnosis and photodynamic therapy (PDT) with much success. Five ALA-based drugs have now received worldwide approval and are being used for managing very common human (pre)cancerous diseases such as actinic keratosis and basal cell carcinoma or guiding the surgery of bladder cancer and high-grade gliomas, making it the most successful drug discovery and development endeavor in PDT and photodiagnosis. The potential of ALA-induced PpIX as a fluorescent theranostic agent is, however, yet to be fully fulfilled. In this review, we would like to describe the heme biosynthesis pathway in which PpIX is produced from ALA and its derivatives, summarize current clinical applications of ALA-based drugs, and discuss strategies for enhancing ALA-induced PpIX fluorescence and PDT response. Our goal is two-fold: to highlight the successes of ALA-based drugs in clinical practice, and to stimulate the multidisciplinary collaboration that has brought the current success and will continue to usher in more landmark advances.<\/jats:p>","DOI":"10.3390\/bioengineering10040496","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T02:05:31Z","timestamp":1682042731000},"page":"496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2335-770X","authenticated-orcid":false,"given":"Richard","family":"Howley","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, Saint Joseph\u2019s University, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharayu","family":"Chandratre","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, Saint Joseph\u2019s University, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, Saint Joseph\u2019s University, Philadelphia, PA 19104, USA"},{"name":"Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1562\/0031-8655(2001)0740656THOPAP2.0.CO2","article-title":"The History of Photodetection and Photodynamic Therapy","volume":"74","author":"Ackroyd","year":"2007","journal-title":"Photochem. 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