{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T05:39:52Z","timestamp":1777268392416,"version":"3.51.4"},"reference-count":41,"publisher":"Open Exploration Publishing","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Explor Target Antitumor Ther"],"accepted":{"date-parts":[[2026,3,30]]},"abstract":"<jats:p xml:lang=\"en\">Background: Targeted radioligand therapy (TRT) is an emerging theranostic modality in oncology. While well established in neuroendocrine and prostate cancers, its role in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) remains investigational. This systematic review summarizes current evidence evaluating TRT in lung cancer. Methods: A Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-guided systematic review of PubMed, Embase, and Scopus (2000\u2013November 2025) was conducted. Original studies evaluating TRT in SCLC or NSCLC were included. Primary outcomes were tumor response, disease-control rate, and treatment-related toxicity. Secondary outcomes included progression-free survival, overall survival, and dosimetry. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies\u2014of Interventions (ROBINS-I) tool. Results: From 2,453 records, 15 studies were included, reporting 358 lung cancer patients, of whom 105 received TRT. Disease-control rates reached up to 78% in mixed NSCLC\/SCLC cohorts. In SCLC, somatostatin receptor-targeted peptide receptor radionuclide therapy demonstrated heterogeneous disease control (0\u201350%), with [177Lu]Lu-labeled agents showing more favorable outcomes than [90Y]Y-based therapy. The most favorable outcomes were a median progression-free survival of 11.9 months and an overall survival of 16 months in responders. In NSCLC, fibroblast activation protein (FAP)-targeted agents such as [177Lu]Lu-FAP-2286 demonstrated partial metabolic responses, including a 44.4% response rate and 78% disease control in a mixed cohort. Severe toxicities were infrequent. Discussion: TRT is a promising but experimental option for advanced lung cancer. Early efficacy signals exist for strong somatostatin receptor (SSTR)-targeted therapy in SCLC and FAP-targeted therapy in NSCLC, but evidence remains limited. Prospective trials with standardized protocols and dosimetry are needed to define TRT\u2019s role in lung cancer treatment.<\/jats:p>","DOI":"10.37349\/etat.2026.1002368","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T04:54:22Z","timestamp":1777265662000},"update-policy":"https:\/\/doi.org\/10.37349\/open_exploration_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The evolving role of targeted radioligand therapy in small cell and non-small cell lung cancer: a systematic review"],"prefix":"10.37349","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9065-3715","authenticated-orcid":false,"given":"Serin","family":"Moghrabi","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saad","family":"Ruzzeh","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamal","family":"Al-Rabi","sequence":"additional","affiliation":[{"name":"Medical Oncology and Hematology Department, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Abdlkadir","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed J.","family":"Al-Jaghbeer","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Department, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nouraldeen","family":"Alzorgan","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ula Al","family":"Rasheed","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Alqudah","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hashemite University (HU), Zarqa 13133, Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0978-4716","authenticated-orcid":false,"given":"Akram","family":"Al-Ibraheem","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, King Hussein Cancer Center (KHCC), Amman 11941, Jordan; 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