Alternative and New Radiopharmaceutical Agents for Lung Cancer

Abstract

Background: FDG PET/CT imaging has an established role in lung cancer (LC) management. Whilst is a sensitive technique, FDG PET/CT has a limited specificity in the differentiation between LC and benign conditions and is not capable of defining LC heterogeneity since FDG uptake varies between hystotypes. Objective: To get an overview about new radiopharmaceuticals for the study of cancer biology features beyond glucose metabolism in LC. Methods: A comprehensive literature review of PubMed/Medline was performed using a combination of the following keywords: “positron emission tomography”, “lung neoplasms”, “non-FDG”, “radiopharmaceuticals”, “tracers”. Results: Evidences suggest that proliferation markers, such as 18F-Fluorothymidine and 11C-Methionine, improve LC staging and are useful in evaluating treatment response and progression free survival. 68Ga-DOTA-peptides are already routinely used in pulmonary neuroendocrine neoplasms (NENs) management and should be firstly performed in suspected NENs. 18F-Fluoromisonidazole and other radiopharmaceuticals show a promising impact on staging, prognosis assessment and therapy response in LC patients, by visualizing hypoxia and perfusion. Radiolabeled RGD-peptides, targeting angiogenesis, may have a role in LC staging, treatment outcome and therapy. PET radiopharmaceuticals tracing a specific oncogene/signal pathway, such as EGFR or ALK, are gaining interest especially for therapeutic implications. Other PET tracers, like 68Ga-PSMA-peptides or radiolabeled FAPIs, need more development in LC, though, are promising for therapy purposes. Conclusion: To date the employment of most of the described tracers is limited to the experimental field, however, research development may offer innovative opportunities to improve LC staging, characterization, stratification and response assessment in an era of increased personalized therapy.

Modern radiopharmaceuticals for lung cancer imaging with positron emission tomography/computed tomography scan: A systematic review

“…Telo et al 12 in a review for alternative and new radiopharmaceutical agents for lung cancer considered that FDG-PET/ CT has major contribution to lung cancer management. Although FDG-PET/CT has a satisfying sensitivity, its specificity is limited because of the weakness to distinguish benign conditions from lung cancer and its inability to define lung cancer heterogeneity between different subtypes according to FDG uptake.…”

“…They also marked that radiopharmaceutical agents, which target into a specific oncogene/signal pathway like anaplastic lymphoma kinase (ALK) or epidermal growth factor receptor (EGFR), gain ground for curative intents. 12 PET tracers such as 68 GA-PSMA or radio-labeled fibroblast-activation-protein-inhibitors (FAPIs) require further investigation but are promising for curative implications.…”

“…Huang 3 quoted the 89 Zr-Ibritumomab for assessment, prediction, and optimization of therapeutic dose in 90 Y-Ibritumomab patients with Non-Hodgkin Lymphoma (NHL). Telo et al 12 concluded that the traces 68 GA-PSMA, radio-labeled FAPIs, specific oncogene/signal pathway, such as ALK or EGFR, and RGD peptides are in the experimental level, and more scientific research and development are needed in order to reach in the absolute personalized therapy through the proper lung cancer staging, characterization, and response evaluation.…”

Positron emission tomography imaging of lung cancer: An overview of alternative positron emission tomography tracers beyond F18 fluorodeoxyglucose

“…However, since tissue glucose metabolism is not malignancy specific, other conditions, such as inflammatory/infective processes, will also cause increased 18 F-FDG uptake and false-positive results ( 16 , 17 ). Furthermore, a great amount of tumor heterogeneity can be found in all histologic subtypes of LC, and 18 F-FDG uptake is variable in different subtypes: SCC displays higher FDG-avid than adenocarcinomas, while pulmonary NETs, lepidic predominant adenocarcinomas and mucinous neoplasms usually show relatively low 18 F-FDG uptake ( 18 , 19 ). Heterogeneity may present in different lesions within the same patient.…”

Quantification and reliability of [11C]VC - 002 binding to muscarinic acetylcholine receptors in the human lung — a test-retest PET study in control subjects

“…PET-examination of lung tissue has long been dominated by tumor imaging using the radiotracer 2-Deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) which serves as a critical tool for the diagnosis of lung cancer and monitoring of different therapies [2,3]. Besides the wide use of [ 18 F]FDG, a series of new radioligands aimed to examine lung cancer biology and to improve tumor management has been recently introduced into clinical routine [4]. In addition, a small number of studies have been published on deposition of radiolabeled drugs in the lungs [5][6][7], Importantly, some attempts have also been made to measure receptor binding in the lungs, for instance beta-adrenoreceptors [8], muscarinic acetylcholine receptors (mAChRs) [9], opioid receptors [10] and epidermal growth factor receptor mutational status [11].…”