Co, Fe and Ga chelates for cell labelling: a potential use in PET imaging?

A high-affinity [18 F]-labeled phosphoramidate peptidomimetic PSMA-targeted inhibitor for PET imaging of prostate cancer

IntroductionDistinct physiological states arise from complex interactions among the various organs present in the human body. PET is a non-invasive modality with numerous successful applications in oncology, neurology, and cardiology. However, while PET imaging has been applied extensively in detecting focal lesions or diseases, its potential in detecting systemic abnormalities is seldom explored, mostly because total-body imaging was not possible until recently.MethodsIn this context, the present study proposes a framework capable of constructing an individual metabolic abnormality network using a subject’s whole-body 18F-FDG SUV image and a normal control database. The developed framework was evaluated in the patients with lung cancer, the one discharged after suffering from Covid-19 disease, and the one that had gastrointestinal bleeding with the underlying cause unknown.ResultsThe framework could successfully capture the deviation of these patients from healthy subjects at the level of both system and organ. The strength of the altered network edges revealed the abnormal metabolic connection between organs. The overall deviation of the network nodes was observed to be highly correlated to the organ SUV measures. Therefore, the molecular connectivity of glucose metabolism was characterized at a single subject level.ConclusionThe proposed framework represents a significant step toward the use of PET imaging for identifying metabolic dysfunction from a systemic perspective. A better understanding of the underlying biological mechanisms and the physiological interpretation of the interregional connections identified in the present study warrant further research.

How far is arterial spin labeling MRI from a clinical reality? Insights from arterial spin labeling comparative studies in Alzheimer's disease and other neurological disorders.

1. How should 99mTc sestamibi be administered when used for breast tumor imaging? (a) Intramammary injection (b) Via indwelling catheter (c) Via intravenous injection in the arm contralateral to involved breast (d) None of the above (e) (b) and (c) 2. What is the optimal scanning time for neoplasm when using 67Ga citrate? (a) 4 h (b) 6 h (c) 24 h (d) 48 h 3. Lymphoscintigraphy is used to: (a) Map lymphatic channels (b) Determine drainage pathways from malignant neoplasms (c) Identify the sentinel node (d) All of the above (e) (a) and (b) only 4. 111In pentetreotide is a: (a) Potassium analog (b) Monoclonal antibody (c) Somatostatin analog (d) Radiocolloid 5. A HAMA response occurs because: (a) A kit contains pyrogens. (b) Monoclonal antibodies are produced from mouse cells which the human body recognizes as a foreign protein. (c) A patient is allergic to 111In. (d) Monoclonal antibodies are produced from human cells that trigger an immune response in the patient. 6. A dose of 111In satumomab pendetide should be _____ before injection. (a) Shielded (b) Filtered (c) Assayed (d) All of the above (e) (a) and (c) only 7. 111In satumomab pendetide is used to image: (a) Extrahepatic metastases from colorectal and ovarian cancer (b) Breast tumors (c) Neuroendocrine tumors (d) Lymphatic channels 8. Advantages of 201Tl chloride over 67Ga citrate include: (a) Much shorter half-life. (b) Less uptake in inflammatory processes. (c) Imaging may take place sooner. (d) All of the above. (e) (b) and (c) only. 9. It is possible to use 99mTc sestamibi for breast tumor imaging because there is no uptake of sestamibi in the normal breast. (a) True (b) False 10. A monoclonal antibody is developed which displays cross-reaction. This means: (a) The antibody triggers an immune response in the patient. (b) The antibody will bind antigens other than the one it was formed with. (c) The antibody can be labeled with either 99mTc or 111In. (d) None of the above. 11. Examples of neuroendocrine tumor include: (a) Pituitary adenoma (b) Small-cell lung cancer (c) Neuroblastomas (d) All of the above (e) (a) and (c) only 12. Visualization of kidneys at 48 h is _____on a scan using 111In pentetreotide and _____on a 67Ga citrate scan. (a) Normal, abnormal (b) Abnormal, normal (c) Normal, normal (d) Abnormal, abnormal 13. 18FDG can be used to image tumors because the glycolytic rate is higher in tumor than in normal tissues. (a) True (b) False 14. Which of the following are true regarding 18FDG tumor imaging? (a) PET scanning is required. (b) The patient should fast before the exam. (c) Only brain tumors can be detected. (d) All of the above. (e) All except c. 15. On a Monday morning, a technologist learns that a patient needs to be scheduled for imaging with 67Ga citrate and also a lower GI. If the ordering physician wishes that both exams be done within the week, how should these studies be scheduled? (a) Lower GI on Monday morning and 67Ga citrate on Monday afternoon. (b) Lower GI on Monday morning and 67Ga citrate on Wednesday. (c) 67Ga injection on Monday morning followed by imaging each day and lower GI at noon on Friday. (d) Inject patient with 67Ga citrate on Monday morning, send for lower GI, and then perform first imaging of gallium on Monday afternoon. 16. Pheochromocytomas are imaged using: (a) 131I MIBG (b) 131I NP-59 17. The use of PET imaging in oncology takes advantage of the _____differences between normal and neoplastic tissue. (a) Structural (b) Metabolic (c) Density (d) Hormonal 18. Hodgkin’s disease is a type of: (a) Lung cancer (b) Lymphoma (c) AIDS (d) Lupus 19. Normal areas of uptake for 67Ga citrate include all of the following except: (a) Intestinal mucosa (b) Parathyroid glands (c) Liver (d) Epiphyses in pediatric patients 20. If a low-energy collimator is used for imaging 67Ga, what will the effect be? (a) There is increased septal penetration. (b) Poor spatial resolution. (c) Decreased sensitivity. (d) (a) and (c). (e) (a) and (b). 21. F-18 fluciclovine is currently an FDA-approved imaging agent for what type of cancer? (a) Thyroid cancer (b) Lung cancer (c) Liver cancer (d) Prostate cancer 22. What is the half-life of Ga-68 dotatate? (a) 68 min (b) 78 h (c) 6 h (d) 110 min 23. Recommended dose for imaging with Ga-68 dotatate? (a) 10 mCi (b) 15 mCi (c) 20 mCi (d) 0.054 mCi/kg up to 5.4 mCi 24. Gallium-68 is ___________ produced. (a) Generator (b) Cyclotron 25. Gallium-68 dotatate is indicated for imaging what type of cancers utilizing PET? (a) Small-cell lung cancer (b) Neuroendocrine tumors (c) Prostate cancer (d) Breast cancer 26. Recommended dose for imaging with F-18 fluciclovine? (a) 10 mCi (370 MBq) (b) 5 mCi (c) 20 mCi

Background and aim: Labeled leukocytes with 99mTc-HMPAO are routinely used for infection imaging. Although cell labeling with 99mTc-HMPAO represents an imaging probe to detect infection sites, the diagnostic efficiency of the probe is largely influenced by cell manipulation, multidisciplinary interventions (i.e., biologist, technicians) and available technology (i.e., SPECT, SPECT/CT). The aim of the study was to assess in vitro and in vivo accuracy of a comprehensive approach for quality assessment (QA) of all steps of the procedure. Methods: Radiochemical purity (RCP), pH, labeling efficiency (LE) were measured in 320 procedures. White Cell Viability Factor (WVF) was determined in consecutive blood samples. Images (490 studies) were scored using a 5-point scale. Training program was evaluated using a Learning Questionnaire and a score system. Results: Pre/post-labelling WVF was 0.99% (max value 1%) in all blood samples. LE (mean value 72%) and RCP (>80% until 55 minutes) yielded considerably high values. The vast majority of images were scored as diagnostic by three independent observer (90% with score ≥4). Conclusions: This method appears highly reproducible and easy to use in clinical routine for leukocyte labeling, especially when standardized training and total QA system are implemented. (www.actabiomedica.it)

Alan Hofmann has been a leader in the field of bile acids for much of his 6- decade career. In his Master's Perspective published in Hepatology in 2009, Alan entitled his journey as "Bile Acids: Trying to Understand Their Chemistry and Biology with the Hope of Helping Patients". He clearly achieved those ambitious goals, driving forward our understanding of these complex molecules with a highly energetic, engaging and encouraging manner that touched nearly every member of the bile acid field.

Introduction: An appropriate use criteria workgroup recently recommended the use of PET imaging utilizing the 16α-18F-fluoro-17β-fluoroestradiol (FES) radiotracer as a measure of disease progression and endocrine treatment response for ER-positive breast cancers. Past studies report limitations of decreased FDG uptake, the most common PET radiotracer, when measuring low Ki-67 scoring tumors; FES-PET may noninvasively address this shortcoming in FDG activity detection. Its benefit of detecting low-grade, ER-positive tumor activity was demonstrated in a patient with breast cancer who exhibited tumor growth only on FES-PET while FDG-PET showed no measurable disease. Clinical Case: A 57-year-old postmenopausal woman presented in December 2017 with de novo metastatic invasive ductal carcinoma that was ER+ (100%), PR+ (100%), and HER2- involving the right breast, bone, lungs, and internal mammary, subcarinal, and right hilar lymph nodes. She received nab-paclitaxel and radiation to the right breast, regional lymph nodes, and T11 bone. In March 2019, she underwent a right mastectomy with pathology that noted residual disease in the breast measuring <5 mm and was placed on exemestane in April 2019. She transferred her care to City of Hope and follow-up FDG-PET restaging showed no evidence of new metabolically active metastatic disease. Her cancer antigen 27.29 levels were also within normal limits. In the absence of measurable disease growth, she continued to be treated with single agent exemestane. Due to persistent back discomfort that she attributed to breast asymmetry, she requested the left breast to be removed. One week prior to surgery, both FDG-PET/CT and bloodwork inclusive of tumor markers were normal. She underwent a left mastectomy in March 2023. Pathology identified an incidental 1.4 cm lymph node in the 2000 g specimen that was ER+ (>95%), PR-, and HER2- with a Ki-67 of 1-3%. Somatic gene testing of the tumor revealed an ESR1 D538G mutation. As her progressive disease was not evident on previous FDG-PET imaging, an FES-PET/CT was performed and demonstrated uptake in the ilium, T10, and T12 bones that was not identified on FDG-PET/CT. With objective evidence of evaluable disease, exemestane was discontinued and fulvestrant and ribociclib were initiated. Clinically, she has evidence of early response to therapy with improvement in back pain. Discussion: This case demonstrates the value of FES-PET/CT in identifying disease that was not appreciated on FDG-PET/CT or by cancer antigen 27.29 monitoring. Additionally, ESR1 status has not been consistently reported in studies of patients undergoing FES-PET imaging that investigate the radiotracer’s value in predicting response to subsequent endocrine therapy. Our patient has a documented ESR1 mutation, her disease was clearly identified only on FES-PET/CT, and FES uptake predicted for response to subsequent endocrine therapy. Incorporating FES-PET in routine staging should be considered in patients with metastatic breast cancer that is low-grade and ER-positive. Further evidence of response prediction in patients with ESR1 mutations will enhance the utility of FES-PET in the clinical management of these patients. Citation Format: Megan Wong, Veronica Jones, Dave Yamauchi, Joanne Mortimer. Value of 16α-18F-fluoro-17β-fluoroestradiol PET imaging in ER-positive breast cancer: a case report [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-20-10.

The role of PET imaging in the management of patients with central nervous system disorders

Cyclotron production of 44Sc: From bench to bedside

The detection of lymphoma by computed tomography (CT) scanning is known to be improved by positron emission tomography (PET) and/or gallium scanning, although the direct comparative accuracy of these imaging modalities remains a subject of ongoing review. The aim of the present study was to compare PET scanning with conventional imaging (CT and/or gallium scanning) in patients with lymphoma. A retrospective study of 38 patients (25 men; 13 women; median age 39.5 years; range 18.0-81.0 years) who had had PET scans (24 scans at initial staging and 46 scans at restaging, including suspected disease relapse) was carried out. Thirty-one concurrent gallium scans had been performed. Disease was validated with clinical follow up or biopsy. The sensitivities of PET and CT at initial staging were 96 and 71%, respectively. PET identified additional sites of disease compared with CT in 29% of patients. Of the 15 patients who had had all three imaging modalities, the sensitivities of PET, CT and gallium were 93, 67 and 87%, respectively. At treatment completion, the positive predictive values of PET, CT and gallium scans for relapse given a residual mass were 100, 33 and 0%, respectively (P = 0.006 for PET and CT comparison). The negative predictive values of PET, CT and gallium were 76, 0 and 70%, respectively (P-value not significant). In suspected disease relapse, PET results changed management in 50% of patients. Compared with CT and gallium scans, PET has superior accuracy in staging and restaging, and its greatest value lies in its positive predictive value for relapse in patients with residual masses.

The significance of metastasis is well addressed by a truism in the cancer field asserting that patients succumb to metastasis, not their primary tumor. Upon diagnosis and treatment, tumor cells may have already disseminated to distant sites, surviving in the form of occult minimal residual disease (micrometastasis) that can remain ‘clinically dormant’ for years. Once these cells break dormancy, they can evolve into clinically significant lesions, the macrometastases. The transition to macrometastasis is considered a hallmark of cancer progression, ultimately responsible for the majority of cancer-related deaths. After surgical removal of tumors, adjuvant therapies are often initiated to prevent metastatic colonization. For melanoma, the situation is particularly grave, as metastatic melanoma is notoriously resistant to therapies and is regarded as virtually incurable. For preclinical studies, the complex metastatic process, consisting of dissemination, dormancy, outbreak, and regrowth, needs to be carefully monitored in a noninvasive manner. Two major types of imaging technologies have been developed for in vivo tracking of disseminated malignant cells in animal models. Optical imaging detects visualized wavelengths generated from a luminescent reaction (e.g. luciferase) or an excited fluorescent chromophore [e.g. green fluorescent protein (GFP)]. It is real time, cost-effective, and time efficient, but is limited by the tissue absorption of the emitted light and lower resolution. The other type is tomography – imaging by sectioning using penetrating waves, including X-ray [computer-aided tomography (CAT)], magnetic field [magnetic resonance imaging (MRI)], and other ionizing radiation [positron emission tomography (PET) and single-photon emission computed tomography (SPECT)]. Tomography gives high-resolution, 3-D images; however, the scanning and image reconstruction are relatively time-consuming processes using expensive instruments. PET and SPECT are especially useful for cancer research, because they can detect radiotracers preferentially retained in cancer cells, giving the highest specificity in tumor diagnosis. Among these methods, optical imaging and SPECT require cell labeling with marker genes to produce optical signals and metabolizing radiotracers, respectively. Although cell labeling greatly enhances in vivo tracking in preclinical studies, it is often discouraged because of tedious labeling and selection procedures, low labeling efficiency and specificity, and inconsistent expression of biomarker genes. Given these many issues, it is not surprising that surface-transplanted primary tumor models still dominate the preclinical landscape of cancer therapeutics. Recently, advances in the identification of promoters capable of driving persistent gene expression and efficient lentiviral vector designs have greatly improved the efficiency and consistency of tumor labeling (Day et al., 2009), making it feasible to devise mouse models of metastasis for testing anticancer drug efficacy. However, there remains no ubiquitous, routine method for tumor labeling and in vivo tracking. It would be highly advantageous to treat metastatic disease with a systemic therapy specifically targeting cancer cells; cancer gene therapy has been regarded to possess such potential. Historically, gene therapy was designed to ‘rescue’ a genetic disease by delivering a particular gene to the cells deficient of its function. This purpose requires permanent expression of the delivered genes; thus, retroviral vectors are usually used to achieve genomic integration. In contrast, cancer gene therapy attempts to deliver into cancer cells an inhibitory or cytotoxic gene to cripple or kill them. Therefore, the therapeutic gene could be expressed transiently, permitting the use of non-integration delivery vehicles such as adenovirus, polymer or liposome, which provide a safety advantage in clinical studies. In recent years, improvements in cancer gene therapy have focused on specificity, either by using a control sequence in the DNA vector, such as a cancer-specific promoter, or by adding a tumor-targeting receptor/ligand into the delivery vehicle. These modifications have greatly enhanced the potential for therapeutic versatility. Several cancer gene therapies have advanced to clinical trials, and tumor responses have been observed (Rau et al., 2006). However, rare but possible gene integration events and more complicated and costly components have limited the clinical development of cancer gene therapy. Nevertheless, it is still regarded as one of the best platforms to test and validate therapeutic targets. In a recent issue of Nature Medicine, Bhang et al. have reported a novel use of a cancer gene therapy approach to overcome some of these problems. Previously, the authors identified that the promoter of a DNA damage-responsive gene, protein phosphatase 1 regulatory (inhibitor) subunit 15A (Ppp1r15a, also known as PEG-3), exhibited selective activity in transformed cells and a panel of human cancer cells, prompting the authors to suggest its use in cancer-targeted gene therapy (Su et al., 2005). PEG-3 is a truncated and mutated form of GADD34/Myd116, which is not present in the human genome. Its promoter has been used to selectively drive adenovirus replication and expression of a therapeutic cytokine, melanoma differentiation–associated gene-7/interleukin-24 (mda-7/IL-24), in metastatic human melanoma cells resulting in profound antitumor activity in human melanoma nude mouse xenograft models (Sarkar et al., 2008). In the current report, they in fact employed this promoter in a gene therapy setting; however, instead of using it for cancer treatment, they designed an improved smart diagnostic probe. The PEG-3 promoter was employed to drive luciferase gene expression, and the construct was bound by linear polyethylenimine (l-PEI), one of the most widely used cationic polymers for gene delivery. Unlike other gene delivery vehicles that tend to be trapped in specific organs (e.g. lung or liver) such as cationic liposome or adenovirus, the l-PEI/DNA complex can more uniformly distribute throughout the body upon intravenous injection. The authors demonstrated the capacity of their gene therapy approach to monitor the emergence of mouse metastasis with bioluminescence imaging and then confirmed that the cancer specificity was achieved through the PEG-3 promoter, rather than tissue-preferred distribution. Uniform distribution is a critical preclinical feature of their model, ensuring that small metastatic lesions arising in various locations will be detected. However, whether the transient and heterogeneous nature of luciferase expression by systemic gene delivery allows a linear correlation between imaging signal and tumor burden was not determined in this study. Moreover, the tissue-associated scattering of bioluminescence prevented the identification of the precise location of each metastatic nodule. In the second part of this study, the authors therefore modified the setting from a monitoring tool to a sensitive diagnostic probe. They decided to deliver the PEG-3 promoter-driven herpes simplex virus thymidine kinase (HSV-tk) gene into the mouse metastasis model. As expected, the individual metastatic nodules were identified by SPECT following the administration of the radiolabeled nucleoside analog, 2′-fluoro-2′-deoxy-β-d-5-125I-iodouracil-arabinofuranoside (125I-FIAU). Unlike the use of 18F-fluorodeoxyglucose (FDG)-PET, where false-positive signals can result from radiotracer uptake in actively metabolizing organs (e.g. heart, brown fat, and brain), the specific expression of HSV-tk provides much higher cancer specificity for 125I-FIAU-SPECT imaging. Compared to the high resolution of SPECT, bioluminescence imaging readouts are mostly limited to overall tumor burden; however, bioluminescence imaging can be performed relatively rapidly, allowing the analysis of a larger number of mice within a feasible time frame. Therefore, these two methods provide complementary tools that address different purposes for the preclinical analysis of metastasis. Bhang et al. have thus successfully employed a previously defined cancer-specific gene therapy approach to generate a versatile and effective diagnostic method. Because the utility of viral thymidine kinase gene/radiotracer for SPECT tumor detection is currently under clinical investigation, this report provides a potentially clinically relevant method of tumor diagnosis as well. There are a few issues that will require further investigation. Labeling cancer cells via reporter gene delivery results in transient expression of the labeling marker; whether this feature will allow quantitative tracking of the onset time and growth of metastatic disease remains to be established. Also, it will be critical to determine whether in this gene therapy setting delivering a xenobiotic gene with a cationic polymer distorts tumor responses to therapeutic treatment. As PEG-3 promoter activity may vary depending on histological type (Su et al., 2005) and only a small number of melanoma and breast cancer cell lines have been examined, for either clinical or preclinical studies of melanoma, it will also be important to examine the activity of the PEG-3 promoter in additional human and mouse melanoma cell lines. Moreover, to evaluate the accessibility of the PEG-3 promoter-driven luciferase vector and the influence of various microenvironments on promoter activity, this gene therapy approach should be tested in mouse models of metastasis generated using different routes of tumor inoculation (e.g. subcutaneous, intraperitoneal, and intracardiac injection). Nevertheless, the authors’ design effectively bypasses the prerequisite of cancer cell labeling, effectively relaxing a stringent bottleneck to establishing a traceable metastasis model. This report marks significant progress in cell-tracking bioimaging technologies, which will ultimately facilitate the development of both preclinical models of metastatic disease and the drugs to effectively treat it. Hopefully, the work by Bhang et al. will help refocus preclinical efforts toward targeting this most lethal stage of melanoma.

The aim of this study was to evaluate 99Tcm-labelled phenylene imine phenol (99Tcm-Ph(IP)2) as a leukocyte label. The 99Tcm complex exhibits a neutral lipophilic character. The radiochemical purity of the 99Tcm-Ph(IP)2 was high both soon after labelling (94.5 +/- 1.2%, n = 7) and at 24 h (89.7 +/- 1.0%, n = 7). In a comparative study, the labelling efficiency of 99Tcm-Ph(IP)2 and 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) labelled leukocytes was 47.1 +/- 3.5% (n = 7) and 58.5 +/- 7.0% (n = 7) respectively. The viability of labelled leukocytes was greater than 90% for both 99Tcm complexes. The elution ratios of labelled leukocytes with 99Tcm-Ph(IP)2 at 1, 4 and 24 h were 10.1 +/- 3.5%, 17.2 +/- 2.7% and 23.0 +/- 2.4% (n = 7) respectively, while those with 99Tcm-HMPAO were 10.8 +/- 1.2%, 18.3 +/- 2.0% and 37.0 +/- 3.7% (n = 7) respectively. In conclusion, 99Tcm-Ph(IP)2, with good stability and significant leukocyte labelling efficiency, is a potential leukocyte label.

Advances in immunoPET/SPECT imaging: The role of Fab and F(ab′)2 fragments in theranostics

PurposeThe aim of this study was to evaluate the clinical value of simultaneous positron emission tomography/computed tomography (PET/CT) and abdominal positron emission tomography/magnet resonance imaging (PET/MRI) in the detection of liver metastases and extrahepatic disease (EHD) in patients with potentially resectable colorectal liver metastases (CLM).MethodsFifty-six patients with CLM underwent conventional imaging (chest and abdomen CT, liver contrast-enhanced CT or MRI) and PET imaging [fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT and subsequent liver PET/MRI] for staging or restaging. Diagnostic ability of PET imaging was compared with conventional imaging. Abnormal findings were correlated with follow-up imaging and/or histology. The influence of the PET imaging findings was categorized for each patient in relation to operability and other significant findings. The clinical management included three modalities (surgery for resectable CLM, unresectable CLM with conversion treatment, and systemic therapy). The clinical impact of the imaging modality was analyzed. The operative histopathological analysis and/or imaging follow-up were performed as the standard of reference.ResultsThis study enrolled a total of 56 patients (median age 60 years, 62.5% were male, 36 with colon cancer and 20 with rectal cancer). For EHD detection, PET/CT detected more EHD than conventional imaging (60.7% vs. 46.4%). PET/CT had different findings in 19 (33.9%) patients, including downstaging in 4 (7.1%) patients and upstaging in 15 (26.8%) patients. For liver lesion detection, PET/MRI showed comparable detection ability with CE-MRI and CE-CT (99.5%, 99.4%, and 86.5%, respectively) based on lesion analysis, much higher than PET/CT (47.5%). PET imaging had a major impact in 10/56 (17.9%) patients (4 from unresectable to resectable, 6 from resectable to unresectable) and a minor impact in 4/56 (7.1%) patients for changing the surgery extent. The therapeutic strategies had been altered in a total of 14/56 patients (25%) after PET/CT and PET/MRI scans.ConclusionThe results of this study indicate that simultaneous 18F-FDG PET/CT and abdominal PET/MRI scans can provide accurate information regarding CLM status and EHD, and can affect the management of 25% of the patients by changing the therapeutic strategies determined by conventional imaging. This new modality may serve as a new one-stop method in patients with potentially resectable CLM.

Prof Salles provided an update on the ongoing first-line follicular lymphoma (FL) studies, demonstrating how analysis of the GALLIUM study data regarding the use of different chemotherapy backbones consistently showed the benefits of obinutuzumab (G) chemotherapy (G-chemo) versus rituximab (R) chemotherapy (R-chemo) in FL patients. An update from the PRIMA study showed that 10-year progression-free survival (PFS) was improved following the use of R maintenance compared with observation following induction. Prof Salles also provided an overview of the RELEVANCE study data, which showed that R plus lenalidomide was not superior to standard R-chemo for the treatment of first-line FL. Prof Seymour presented data showing that two-thirds of premature FL deaths occur in patients experiencing disease progression within 2 years of treatment, highlighting the need to identify patients at early risk of progression. Prof Seymour explored various prognostic and predictive tools that could be used to identify patients at high risk of death, but he noted that until these prognostic tools are available in the clinic, the high-risk population remains unidentifiable. Furthermore, the accuracy of these prognostic indices needs to be improved. Data analysis from the GALLIUM study showed that G-chemo decreased the risk of a disease progression event in the first 2 years by 46% compared to R-chemo. Prof Trotman explored the use of PET imaging and detection of minimal residual disease (MRD) to assess treatment outcomes. Prof Trotman showed that PET status at the end of induction is highly prognostic of the outcome. An exploratory analysis of the GALLIUM data showed that the application of the Lugano 2014 response criteria showed a rapid, deep separation of the PFS curves of patients achieving a complete metabolic response (CMR) versus those who did not. There was almost a 5-fold increase in risk of progression and in risk of death in patients failing to achieve CMR. An exploratory analysis of the MRD status of GALLIUM patients showed that a greater proportion of patients in the G-chemo arm achieved MRD-negative status at the end of induction (EOI). Interestingly, patients achieved similar MRD outcomes with G-chemo, regardless of chemotherapy backbone. Both PET and MRD status after induction were independently predictive of PFS. Dr Pettengell and Mr Bouguet discussed FL from both the clinician’s and the patient’s perspective, with a focus on health-related quality of life (HRQoL). They demonstrated how a marked decrease in HRQoL at progression highlights the importance of extending remission for FL patients. Dr Pettengell presented data from GALLIUM showing comparable quality of life for patients treated with either G-chemo or R-chemo. They also presented patient surveys showing that FL has a substantial physical and psychological impact on patients that both lasts beyond treatment and persists even during long-term remission.