Triple-negative breast cancer is a subtype of breast cancer for which [18F]FDG PET imaging has limitations. Fibroblast activation protein, which is overexpressed in the tumor microenvironment, is a promising target for imaging these cancers. This study is part of the PRECISION clinical trial, promoted by the Centre Henri-Becquerel, which aims to evaluate whether [68Ga]Ga-FAPI-46 PET imaging can predict the oncological response to neoadjuvant chemo-immunotherapy. As [68Ga]Ga-FAPI-46 is an experimental drug without marketing authorization in France, its production requires regulatory approval from the French National Agency for Medicines and Health Products Safety (ANSM) via the submission of a Common Technical Document (CTD). The radiosynthesis of [68Ga]Ga-FAPI-46 was performed using a Trasis Mini AIO automated system. [68Ga]GaCl3 was obtained by elution from a GalliaPharm generator. Labeling was performed by heating the FAPI-46 precursor with [68Ga]GaCl3 at 95°C for 10minutes, followed by purification by solid-phase extraction and terminal sterilizing filtration. Validation of the method required seven syntheses, including the establishment of rigorous quality controls in accordance with the European Pharmacopoeia. The main controls performed were: radiochemical purity by HPLC and TLC, identification of [68Ga]Ga, stability by forced degradation at 35°C, microbiological tests (sterility, bacterial endotoxins), organoleptic characteristics, and pH. The analytical methods demonstrated compliance with the validation criteria for frontal ratio, precision, robustness, and linearity. The three validation batches required for the CTD met all release criteria, confirming the reliability of the method. The automated synthesis method for [68Ga]Ga-FAPI-46 using the Mini-AIO automated system and the Eckert generator was successfully validated. The analytical and quality control data will subsequently enable the CTD to be submitted to the ANSM, allowing the experimental radiopharmaceutical to be used in the PRECISION clinical trial.

Prostate cancer (PCa) has been identified as the most prevalent form of cancer among males and the third leading cause of death from cancer in the European male population. Early-stage PCa can be treated with prostatectomy and radiotherapy, whereas metastatic cases require androgen deprivation therapy and may benefit from targeted radionuclide therapy (TRT). The objective of our research is to develop and validate an automated production of [177Lu]Lu-PSMA I T for clinical use. [177Lu]Lu-PSMA I T is a radioligand therapy (RLT) that targets prostate-specific membrane antigen (PSMA), which is overexpressed in metastatic and castration-resistant prostate cancer. This work delineates the development and validation of analytical methodologies for the automated production of [177Lu]Lu-PSMA I T with a GAIA-LUNA device from Elysia, in addition to the quality control measures implemented to ensure compliance with Good Manufacturing Practices and the European Pharmacopoeia. Three validation batches were produced, and the investigational medicinal product dossier was submitted to the French National Agency of Medicine and Health Products Safety (ANSM) for authorization. PSMA-I T was radiolabeled with 177Lu using an automated radiosynthesis device, the GAIA-LUNA, from Elysia. Furthermore, we demonstrated the 72-h stability of the [177Lu]Lu-PSMA I T preparations at room temperature, a development that facilitates the potential subcontracting of [177Lu]Lu-PSMA I T production to other medical facilities. The findings of this study underscore the potential of [177Lu]Lu-PSMA I T as a therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC) who have contraindications to chemotherapy or hormonotherapy, and highlight the importance of implementing rigorous quality control measures in the development of radiopharmaceuticals.

Single photon emission computed tomography (SPECT/CT) using meta-iodobenzylguanidine (mIBG) is currently recommended in pediatric clinical guidelines for assessing neuroblastoma. However, [¹²³I]-mIBG scintigraphy may sometimes be less sensitive than positron emission tomography/computed tomography (PET/CT) using [¹⁸F]-FDOPA. In order to enhance diagnostic reliability and minimize the risk of missing lesions, both nuclear medicine imaging modalities were used here. We present a case study of a newborn girl who was diagnosed with neuroblastoma in utero. [18F]-FDOPA PET/CT scans showed faint uptake related to the lesion, whereas [123I]-mIBG scintigraphy was more sensitive and correlated with an MRI-suspicious mass. The metabolic pathways explored by the two tracers are different and sometimes complementary. [123I]-mIBG has an affinity for the norepinephrine transporter, whereas [18F]-FDOPA has an affinity for the large neutral amino acid transporter-1. The role of [¹⁸F]-FDOPA PET/CT in neuroblastoma is evolving and has been demonstrated to have high sensitivity, but surprisingly, in this particular case, it has limited specificity for neuroblastoma, which was taken into account when interpreting the [18F]-FDOPA PET/CT scan.

Le Locametz® (gozétotide) est un médicament radiopharmaceutique prescrit pour le diagnostic des tumeurs de la prostate exprimant l'antigène membranaire spécifique de la prostate (PSMA). D'après les instructions de préparation du Locametz® fournies dans le RCP, celui-ci doit être incubé pendant au moins 5 minutes à température ambiante (25 ± 5 °C) après élution du gallium-68 dans le flacon. Des contrôles qualité (CQ), dont l'évaluation de la pureté radiochimique (PRC) et du pH, doivent être réalisés avant son administration au patient. La PRC doit être supérieure à 97 % et le pH doit être compris entre 3,2 et 6,5. Dans notre établissement, le Locametz® est conservé au réfrigérateur entre 2 et 8 °C. L'objectif de cette étude est d'évaluer l'influence des paramètres physicochimiques (pH, température) sur la pureté radiochimique du Locametz® obtenue après marquage au gallium-68. Le chlorure de gallium-68 a été obtenu en éluant par aspiration un générateur Eckert & Ziegler GalliaPharm® (5 mL d'acide chlorhydrique 0,1 N). La trousse de Locametz® présentait une température de 2,4 °C au moment de l'emploi. Les caractères organoleptiques, le pH et la pureté radiochimique ont été déterminés à des temps d'incubation distincts : 5 min, 10 min, 15 min et 35 min. La PRC a été déterminée par chromatographie sur couche mince instantanée (ITLC) selon les recommandations du RCP. Un marquage du Locametz® après retour à température ambiante de la trousse a été réalisé pour comparaison. Au total, le marquage réalisé avec le flacon de Locametz® conservé au réfrigérateur, les puretés radiochimiques obtenues à 5 min, 10 min, 15 min et 35 min ont été évaluées. Elles étaient, respectivement, de 46 %, 58 %, 61 % et 81 %. Le pH obtenu était compris entre 3 et 3,5. Tandis que le marquage a été réalisé avec le flacon de Locametz® à température ambiante, la pureté radiochimique était supérieure à 97 % après 5 minutes d'incubation et le pH compris entre 3 et 3,5. La mise à température ambiante du flacon de Locametz® avant radiomarquage semblerait nécessaire pour obtenir une pureté radiochimique supérieure à 97 % dans les temps définis par le RCP. Cette étude montre que la température est un paramètre critique dans le radiomarquage du PSMA au gallium-68.

Tumor hypoxia is a complex and evolving phenomenon both in time and space. Molecular imaging allows to approach these variations, but the tracers used have their own limitations. PET imaging has the disadvantage of low resolution and must take into account molecular biodistribution, but has the advantage of high targeting accuracy. The relationship between the signal in MRI imaging and oxygen is complex but hopefully it would lead to the detection of truly oxygen-depleted tissue. Different ways of imaging hypoxia are discussed in this review, with nuclear medicine tracers such as [18F]-FMISO, [18F]-FAZA, or [64Cu]-ATSM but also with MRI techniques such as perfusion imaging, diffusion MRI or oxygen-enhanced MRI. Hypoxia is a pejorative factor regarding aggressiveness, tumor dissemination and resistance to treatments. Therefore, having accurate tools is particularly important.

Intratumoral hypoxia is associated with a poor prognosis and poor response to treatment in head and neck cancers. Its identification would allow for increasing the radiation dose to hypoxic tumor subvolumes. 18F-FMISO PET imaging is the gold standard; however, quantitative multiparametric MRI could show the presence of intratumoral hypoxia. Thus, 16 patients were prospectively included and underwent 18F-FDG PET/CT, 18F-FMISO PET/CT, and multiparametric quantitative MRI (DCE, diffusion and relaxometry T1 and T2 techniques) in the same position before treatment. PET and MRI sub-volumes were segmented and classified as hypoxic or non-hypoxic volumes to compare quantitative MRI parameters between normoxic and hypoxic volumes. In total, 13 patients had hypoxic lesions. The Dice, Jaccard, and overlap fraction similarity indices were 0.43, 0.28, and 0.71, respectively, between the FDG PET and MRI-measured lesion volumes, showing that the FDG PET tumor volume is partially contained within the MRI tumor volume. The results showed significant differences in the parameters of SUV in FDG and FMISO PET between patients with and without measurable hypoxic lesions. The quantitative MRI parameters of ADC, T1 max mapping and T2 max mapping were different between hypoxic and normoxic subvolumes. Quantitative MRI, based on free water diffusion and T1 and T2 mapping, seems to be able to identify intra-tumoral hypoxic sub-volumes for additional radiotherapy doses.

Glioblastomas (GBMs) are the most common primary brain tumors characterized by strong invasiveness and angiogenesis. GBM cells and microenvironment secrete angiogenic factors and also express chemoattractant G protein-coupled receptors (GPCRs) to their advantage. We investigated the role of the vasoactive peptide urotensin II (UII) and its receptor UT on GBM angiogenesis and tested potential ligand/therapeutic options based on this system. On glioma patient samples, the expression of UII and UT increased with the grade with marked expression in the vascular and peri-necrotic mesenchymal hypoxic areas being correlated with vascular density. In vitro human UII stimulated human endothelial HUV-EC-C and hCMEC/D3 cell motility and tubulogenesis. In mouse-transplanted Matrigel sponges, mouse (mUII) and human UII markedly stimulated invasion by macrophages, endothelial, and smooth muscle cells. In U87 GBM xenografts expressing UII and UT in the glial and vascular compartments, UII accelerated tumor development, favored hypoxia and necrosis associated with increased proliferation (Ki67), and induced metalloproteinase (MMP)-2 and -9 expression in Nude mice. UII also promoted a “tortuous” vascular collagen-IV expressing network and integrin expression mainly in the vascular compartment. GBM angiogenesis and integrin αvβ3 were confirmed by in vivo 99m Tc-RGD tracer imaging and tumoral capture in the non-necrotic area of U87 xenografts in Nude mice. Peptide analogs of UII and UT antagonist were also tested as potential tumor repressor. Urotensin II-related peptide URP inhibited angiogenesis in vitro and failed to attract vascular and inflammatory components in Matrigel in vivo . Interestingly, the UT antagonist/biased ligand urantide and the non-peptide UT antagonist palosuran prevented UII-induced tubulogenesis in vitro and significantly delayed tumor growth in vivo. Urantide drastically prevented endogenous and UII-induced GBM angiogenesis, MMP, and integrin activations, associated with GBM tumoral growth. These findings show that UII induces GBM aggressiveness with necrosis and angiogenesis through integrin activation, a mesenchymal behavior that can be targeted by UT biased ligands/antagonists.

Hypoxic areas are typically resistant to treatment. However, the fluorine-18-fluoroazomycin-arabinoside (FAZA) and fluorine 18 misonidazole (FMISO) tracers have never been compared in non small cell lung cancer (NSCLC). This study compares the capability of 18F-FAZA PET/CT with that of 18F-FMISO PET/CT for detecting hypoxic tumour regions in early and locally advanced NSCLC patients. We prospectively evaluated patients who underwent preoperative PET scans before surgery for localised NSCLC (i.e., fluorodeoxyglucose (FDG)-PET, FMISO-PET, and FAZA-PET). The PET data of the three tracers were compared with each other and then compared to immunohistochemical analysis (GLUT-1, CAIX, LDH-5, and HIF1-Alpha) after tumour resection. Overall, 19 patients with a mean age of 68.2 ± 8 years were included. There were 18 lesions with significant uptake (i.e., SUVmax >1.4) for the F-MISO and 17 for FAZA. The mean SUVmax was 3 (±1.4) with a mean volume of 25.8 cc (±25.8) for FMISO and 2.2 (±0.7) with a mean volume of 13.06 cc (±13.76) for FAZA. The SUVmax of F-MISO was greater than that of FAZA (p = 0.0003). The SUVmax of F-MISO shows a good correlation with that of FAZA at 0.86 (0.66–0.94). Immunohistochemical results are not correlated to hypoxia PET regardless of the staining. The two tracers show a good correlation with hypoxia, with FMISO being superior to FAZA. FMISO, therefore, remains the reference tracer for defining hypoxic volumes.

Objectives. - Last October, the nuclear medicine departments were informed of the closure of the chromium-51 production line for clinical use. This radionuclide has different diagnostic indications in nephrology and hematology. It was therefore essential to set up alternative exploration protocols to overcome this production stoppage. Methods. - Chromium-51 EDTA has been replaced by technetium-99 m DTPA for the determination of glomerular filtration rates. Sodium chromate was substituted by sodium pertechnetate for the determination of globular volumes. A retrospective analysis of the chromium-51 data was performed followed by a prospective study, from January to December 2019 for technetium tracers. Results. - One hundred and forty-four patients were included in the study. Forty-two EDTA-Cr-51 and 30 DTPA-Tc-99m exams were conducted and compared. There were no significant differences between the methods used to assess renal function (P=0.355). For the determination of blood cell and plasma volumes, 47 tests with Cr-51 and (125)l and 25 tests with Tc-99m and (125)l were performed and compared. There were no significant differences in the determination of total (P=0.325) and globular (P=0.148) volumes. Conclusions. - The study carried out shows that there is no significant difference between the results obtained with chromium-51 and technetium tracers. As a result, clinical activity was maintained in good conditions. (C) 2020 Academie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Overexpression of G protein-coupled receptors (GPCRs) in tumours is widely used to develop GPCR-targeting radioligands for solid tumour imaging in the context of diagnosis and even treatment. The human vasoactive neuropeptide urotensin II (hUII), which shares structural analogies with somatostatin, interacts with a single high affinity GPCR named UT. High expression of UT has been reported in several types of human solid tumours from lung, gut, prostate, or breast, suggesting that UT is a valuable novel target to design radiolabelled hUII analogues for cancer diagnosis. In this study, two original urotensinergic analogues were first conjugated to a DOTA chelator via an aminohexanoic acid (Ahx) hydrocarbon linker and then -hUII and DOTA-urantide, complexed to the radioactive metal indium isotope to successfully lead to radiolabelled DOTA-Ahx-hUII and DOTA-Ahx-urantide. The 111In-DOTA-hUII in human plasma revealed that only 30% of the radioligand was degraded after a 3-h period. DOTA-hUII and DOTA-urantide exhibited similar binding affinities as native peptides and relayed calcium mobilization in HEK293 cells expressing recombinant human UT. DOTA-hUII, not DOTA-urantide, was able to promote UT internalization in UT-expressing HEK293 cells, thus indicating that radiolabelled 111In-DOTA-hUII would allow sufficient retention of radioactivity within tumour cells or radiolabelled DOTA-urantide may lead to a persistent binding on UT at the plasma membrane. The potential of these radioligands as candidates to target UT was investigated in adenocarcinoma. We showed that hUII stimulated the migration and proliferation of both human lung A549 and colorectal DLD-1 adenocarcinoma cell lines endogenously expressing UT. In vivo intravenous injection of 111In-DOTA-hUII in C57BL/6 mice revealed modest organ signals, with important retention in kidney. 111In-DOTA-hUII or 111In-DOTA-urantide were also injected in nude mice bearing heterotopic xenografts of lung A549 cells or colorectal DLD-1 cells both expressing UT. The observed significant renal uptake and low tumour/muscle ratio (around 2.5) suggest fast tracer clearance from the organism. Together, DOTA-hUII and DOTA-urantide were successfully radiolabelled with 111Indium, the first one functioning as a UT agonist and the second one as a UT-biased ligand/antagonist. To allow tumour-specific targeting and prolong body distribution in preclinical models bearing some solid tumours, these radiolabelled urotensinergic analogues should be optimized for being used as potential molecular tools for diagnosis imaging or even treatment tools.

What is known and objectives In Europe, the pharmaceutical supply of chromium-51 has been stopped. However, this isotope is necessary for the evaluation of glomerular filtration rates. It is possible to replace it with technetium-99m, but the validation of this change in the measurement method must be carried out. Methods A retrospective analysis of chromium-51 data from January 2018 to January 2019 was performed, followed by a study from January 2019 to January 2020 using the technetium tracer. The patients were different in the both study groups, and none had an eGFR below 50 mL min(-1). A cost analysis was performed. Patient exposure to ionizing radiation was studied for both methods. Results and discussion Seventy-eight patients were included in the study. In total, 42 EDTA-Cr-51 and 36 DTPA-Tc-99m examinations were conducted and compared. There were no significant differences between the methods used to assess renal function (P = .351). The results of cost analysis and patient radiation exposure were in favour of DTPA-Tc-99m examinations. What is new and conclusion Within the limitations of a retrospective study of two patient cohorts, there was no significant difference between the results obtained with chromium-51 and technetium-99m tracers. In addition, with the use of DTPA-Tc-99m, operating costs and patient exposure to ionizing radiation were reduced, and clinical activity was maintained for the patients' benefit. Radiopharmacists are able to react quickly to supply contingencies, reduce operating costs and maintain the quality of medical examinations.

Dinet, Juliette; Tonnelet, David; Le Cloirec, Joseph; Becker, Stéphanie; Bohn, Pierre Author Information

The assessment of tumour response during and after radiotherapy determines the subsequent management of patients (adaptation of treatment plan, monitoring, adjuvant treatment, rescue treatment or palliative care). In addition to its role in extension assessment and therapeutic planning, positron emission tomography combined with computed tomography provides useful functional information for the evaluation of tumour response. The objective of this article is to review published data on positron emission tomography combined with computed tomography as a tool for evaluating external radiotherapy for cancers. Data on positron emission tomography combined with computed tomography scans acquired at different times (during, after initial and after definitive [chemo-]radiotherapy, during post-treatment follow-up) in solid tumours (lung, head and neck, cervix, oesophagus, prostate and rectum) were collected and analysed. Recent recommendations of the National Comprehensive Cancer Network are also reported. Positron emission tomography combined with computed tomography with (18F)-labelled fluorodeoxyglucose has a well-established role in clinical routine after chemoradiotherapy for locally advanced head and neck cancers, particularly to limit the number of neck lymph node dissection. This imaging modality also has a place for the evaluation of initial chemoradiotherapy of oesophageal cancer, including the detection of distant metastases, and for the post-therapeutic evaluation of cervical cancer. Several radiotracers for positron emission tomography combined with computed tomography, such as choline, are also recommended for patients with prostate cancer with biochemical failure. (18F)-fluorodeoxyglucose positron emission tomography combined with computed tomography is optional in many other circumstances and its clinical benefits, possibly in combination with MRI, to assess response to radiotherapy remain a very active area of research.

Les zones hypoxiques sont généralement des zones résistantes au traitement, en particulier à la radiothérapie. Pour le CPNPC, plusieurs études ont proposé d’augmenter la dose de radiothérapie sur ces volumes définis par le FMISO. Dans les cancers de la tête et du cou, la même approche a été utilisée avec le FAZA ou le FMISO, mais ces deux traceurs n’ont jamais été comparés dans le CPNPC. Vingt patients ont été inclus avant chirurgie d’un cancer localisé du CPNPC et ont bénéficié de trois tomographies TEP préchirurgicales : TEP-FDG, TEP-FMISO et TEP-FAZA. Pour chaque patient, les données TEP des trois traceurs ont été comparées entre elles et comparées à l’analyse immunohistochimique (CD34, GLUT-1, CAIX, LDH-5, MCT-4, HIF1-Alpha) après extraction tumorale. 19 patients ont été définitivement inclus dans cet essai : 4 femmes et 15 hommes, avec un âge moyen de 67 ± 7,4 ans. Pour la TEP-FDG, le SUVmax était de 12,3 (± 5,4) et le volume avec un seuil à 40 % du SUVmax était de 23,2 cc (± 19,2). 18 lésions présentaient une absorption significative (SUVmax supérieur à 1,4) pour le MISO et 17 pour le FAZA. Le SUVmax moyen était respectivement de 3 (± 1,36) avec un volume moyen de 25,8 cc (± 25,8) pour FMISO et de 2,16 (± 0,7) avec un volume moyen de 13,06 cc (± 13,76) pour le FAZA. Il existait une excellente corrélation entre le SUVmax FMISO et le SUVmax FAZA à 0,88 (0,72 à 0,95) et une bonne corrélation à 0,73 (0,42 à 0,89) pour le volume avec un seuil à 1,4. Il n’existait pas de corrélation entre le SUVmax FDG et les SUVmax des deux traceurs de l’hypoxie. L’analyse immunohistochimique n’était pas corrélée à l’hypoxie définie par TEP quels que soient les anticorps testés. Cette étude confirme la très bonne corrélation des deux traceurs de l’hypoxie et la supériorité du FMISO sur le FAZA. Malheureusement, il n’existe aucune corrélation avec l’analyse immunohistochimique.

Immunotherapy by using immune checkpoint inhibitors is a revolutionary development in oncology. Medical imaging is also impacted by this new therapy, particularly nuclear medicine imaging (also called radionuclide imaging), which uses radioactive tracers to visualize metabolic functions. Our aim was to review the current applications of nuclear medicine imaging in immunotherapy, along with their limitations, and the perspectives offered by this imaging modality. Method: Articles describing the use of radionuclide imaging in immunotherapy were researched using PubMed by April 2019 and analyzed. Results: More than 5000 articles were analyzed, and nearly 100 of them were retained. Radionuclide imaging, notably 18F-FDG PET/CT, already has a major role in many cancers for pre-therapeutic and therapeutic evaluation, diagnoses of adverse effects, called immune-related adverse events (IrAE), and end-of-treatment evaluations. However, these current applications can be hindered by immunotherapy, notably due to atypical response patterns such as pseudoprogression, which is defined as an increase in the size of lesions, or the visualization of new lesions, followed by a response, and hyperprogression, which is an accelerated tumor growth rate after starting treatment. To overcome these difficulties, new opportunities are offered, particularly therapeutic evaluation criteria adapted to immunotherapy and immuno-PET allowing us to predict responses to immunotherapy. Moreover, some new technological solutions are also promising, such as radiomic analyses and body composition on associated anatomical images. However, more research has to be done, notably for the diagnosis of hyperprogression and pseudoprogression. Conclusion: Immunotherapy, by its major impact on cancer and by the new patterns generated on images, is revolutionary in the field of medical images. Nuclear medicine imaging is already established and will be able to help meet new challenges through its plasticity.

Chemoradiotherapy is the reference curative-intent treatment for nonresectable locally advanced non-small-cell lung carcinoma (NSCLC), with unsatisfying survival partially due to radiation resistance in hypoxic tissues, raising the question of targeted radiotherapy. To evaluate the risk-benefit of radiotherapy boost on hypoxic tumors in NSCLC patients treated by curative-intent chemoradiotherapy in an open-label, nonrandomized, phase II clinical trial developed from 2012 to 2015 with a 3-year follow-up. Multicenter study performed in 15 French academic centers (NCT01576796). Participants: eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. Seventy-nine patients underwent a run-in period, of which 54 were included. Twenty-four patients completed the study at 3 years. 18F-fluoromisonidazole (18F-MISO) positron emission tomography/computed tomography was performed to determine the hypoxic profile of patients (34 positive and 20 negative). Those with positive 18F-FMISO status and without organ-at-risk constraints (n = 24) received radiotherapy boost (70–84 Gy); the others received standard radiotherapy (66 Gy). Overall survival (OS), progression-free survival (PFS), and safety. Hypotheses tested were formulated before data collection. Results: fifty-four patients were evaluated, with a median age of 61 (41–76) years. OS and PFS rates at 1, 2, and 3 years were, respectively, 87%, 58.2%, and 48.5%, and 59.3%, 36.4%, and 28.8%. The median OS in the positive 18F-FMISO group was 25.8 months and was not reached at 3 years in the negative (P = 0.01). A difference was also observed for PFS (12 vs. 26.2 months, P = 0.048). By focusing on positive 18F-FMISO patients, no difference was observed in OS according to the dose, probably because of the small sample size (P = 0.30). However, the median OS seemed to be in favor of boosted patients (26.5 vs. 15.3 months, P = 0.71). In patients who underwent boost, no significant early or late toxicities were observed. 18F-FMISO uptake in NSCLC patients is strongly associated with poor prognosis features. In the group of 18F-FMISO-positive patients, radiotherapy boost seems to improve the OS by 11.2 months. These results deserve further attention in a future clinical trial devoted to hypoxic patients to confirm boost efficacy.

EGFR mutations are routinely explored in lung adenocarcinoma by sequencing tumoral DNA. The aim of this study was to evaluate a fluorescent-labelled erlotinib based theranostic agent for the molecular imaging of mutated EGFR tumours in vitro and ex vivo using a mice xenograft model and fibred confocal fluorescence microscopy (FCFM).