Role of 3'-Deoxy-3'-[18F] Fluorothymidine Positron Emission Tomography-Computed Tomography as a Predictive Biomarker in Argininosuccinate Synthetase 1-Deficient Thoracic Cancers Treated With Pegargiminase.

Introduction: Pegargiminase (ADI-PEG 20I) degrades arginine in patients with argininosuccinate synthetase 1-deficient malignant pleural mesothelioma (MPM) and NSCLC. Imaging with proliferation biomarker 3'-deoxy-3'-[18F] fluorothymidine (18F-FLT) positron emission tomography (PET)-computed tomography (CT) was performed in a phase 1 study of pegargiminase with pemetrexed and cisplatin (ADIPemCis). The aim was to determine whether FLT PET-CT predicts treatment response earlier than CT. Methods: A total of 18 patients with thoracic malignancies (10 MPM; eight NSCLC) underwent imaging. FLT PET-CT was performed at baseline (PET1), 24 hours post-pegargiminase monotherapy (PET2), post one cycle of ADIPemCis (PET3), and at end of treatment (EOT, PET4). CT was performed at baseline (CT1) and EOT (CT4). CT4 (modified) Response Evaluation Criteria in Solid Tumors (RECIST) response was compared with treatment response on PET (changes in maximum standardized uptake value [SUVmax] on European Organisation for Research and Treatment of Cancer-based criteria). Categorical responses (progression, partial response, and stable disease) for PET2, PET3, and PET4 were compared against CT using Cohen's kappa. Results: ADIPemCis treatment response resulted in 22% mean decrease in size between CT1 and CT4 and 37% mean decrease in SUVmax between PET1 and PET4. PET2 agreed with CT4 response in 62% (8 of 13) of patients (p = 0.043), although decrease in proliferation (SUVmax) did not precede decrease in size (RECIST). Partial responses on FLT PET-CT were detected in 20% (3 of 15) of participants at PET2 and 69% (9 of 13) at PET4 with good agreement between modalities in MPM at EOT. Conclusions: Early FLT imaging (PET2) agrees with EOT CT results in nearly two-thirds of patients. Both early and late FLT PET-CT provide evidence of response to ADIPemCis therapy in MPM and NSCLC. We provide first-in-human FLT PET-CT data in MPM, indicating it is comparable with modified RECIST.

The role of new PET tracers for lung cancer.

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) is established for characterising indeterminate pulmonary nodules and staging lung cancer where there is curative intent. Whilst a sensitive technique, specificity for characterising lung cancer is limited. There is recognition that evaluation of other aspects of abnormal cancer biology in addition to glucose metabolism may be more helpful in characterising tumours and predicting response to novel targeted cancer therapeutics. Therefore, efforts have been made to develop and evaluate new radiopharmaceuticals in order to improve the sensitivity and specificity of PET imaging in lung cancer with regards to characterisation, treatment stratification and therapeutic monitoring. 18F-fluorothymidine (18F-FLT) is a marker of cellular proliferation. It shows a lower accumulation in tumours than 18F-FDG as it only accumulates in the cells that are in the S phase of growth and demonstrates a low sensitivity for nodal staging. Its main role is in evaluating treatment response. Methionine is an essential amino acid. 11C-methionine is more specific and sensitive than 18F-FDG in differentiating benign and malignant thoracic nodules. 18Ffluoromisonidazole (18F-FMISO) is used for imaging tumour hypoxia. Tumour response to treatment is significantly related to the level of tumour oxygenation. Angiogenesis is the process by which new blood vessels are formed in tumours and is involved in tumour growth and metastatic tumour spread and is a therapeutic target. Most clinical studies have focused on targeted integrin PET imaging of which αvß3 integrin is the most extensively investigated. It is upregulated on activated endothelial cells in association with tumour angiogenesis. Neuroendocrine tumour tracers, particularly 68Ga-DOTA-peptides, have an established role in imaging of carcinoid tumours. Whilst most of these tracers have predominantly been used in the research environment, they offer exciting opportunities for improving staging, characterisation, stratification and response assessment in an era of increased personalised therapy in lung cancer.

Role of ¹8F-FDG PET imaging in paediatric primary dystonia and dystonia arising from neurodegeneration with brain iron accumulation.

PURPOSE: No current neuroimaging modality offers mechanistic or prognostic information to guide management in paediatric dystonia. We assessed F-fluorodeoxyglucose (¹8F-FDG) PET/computed tomography (CT) brain imaging in childhood primary dystonia (PDS) and neurodegeneration with brain iron accumulation (NBIA) to determine whether it would identify altered metabolism and hence constitute a potentially useful 'biomarker' indicating functional disturbances associated with dystonia and severity of the disease. MATERIALS AND METHODS: A total of 27 children (15 PDS and 12 NBIA) underwent brain ¹8F-FDG PET/CT imaging under anaesthesia during acquisition. The images were assessed visually and the two groups were compared quantitatively with statistical parametric mapping. PET/CT images were spatially transformed to Montreal Neurological Institute standard space. Voxelwise ¹8F-FDG uptake was normalized to whole-brain uptake. Data of both groups were correlated separately with duration and severity of dystonia as assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). RESULTS: Visual inspection did not identify any abnormalities in ¹8F-FDG uptake within the cerebral cortex, basal ganglia, or thalami in either group. Quantitative analysis identified higher uptake in the posterior cingulate and bilateral posterior putamina but decreased uptake in the occipital cortex and cerebellum in NBIA compared with PDS. The NBIA group had more severe dystonia scores compared with the PDS group. BFMDRS was negatively correlated with age but not with duration of dystonia. CONCLUSION: Compared with PDS, NBIA is dominated by relative overactivity in the putamen and by cerebellar underactivity, patterns that may reflect the increased severity of dystonia in NBIA cases. Hence, there is a potential role for ¹8F-FDG PET/CT imaging in paediatric dystonia, particularly in the NBIA group.

The value of semiquantitative analysis in identifying diffuse bone marrow involvement in follicular lymphoma.

AIM: The aim of the study was to investigate the value of fluorine-18-fluorodeoxyglucose ((18)F-FDG)-PET/computed tomography (CT) in identifying diffuse bone marrow (BM) involvement in follicular lymphoma using semiquantitative assessment. METHODS: This is a retrospective analysis of 41 patients with grade 1-3a follicular lymphoma who underwent (18)F-FDG-PET/CT, contrast-enhanced CT and bone marrow trephine biopsy (BMB) as part of staging. BM involvement on PET/CT was assessed by visual and semiquantitative analysis. Standardized uptake values (SUVmax) were measured at the sternum, at both iliac blades and at the T12 vertebra. An average of these four measurements was recorded as SUVav. The single highest overall SUVmax for the four bone sites, the SUVav and the ratios SUVav/mediastinal blood pool (MBP) and SUVav/liver were compared with the BMB result. RESULTS: Focal bone uptake was identified on (18)F-FDG-PET/CT by visual analysis in six patients, including two cases in which the BMB was negative. Assessment of diffuse BM involvement on (18)F-FDG-PET/CT by visual analysis had a sensitivity and specificity of 31 and 92%, respectively. Semiquantitative analysis resulted in an improved sensitivity and specificity of 58 and 96%, respectively, when using SUVav greater than or equal to 2 as the cutoff. Using the ratio SUVav/MBP greater than or equal to 1 the sensitivity of (18)F-FDG-PET/CT to detect BM involvement improved to 83%. CONCLUSION: Visual analysis is useful in determining focal bone involvement, whereas semiquantitative analysis using SUVav/MBP has a high sensitivity and specificity for predicting BM involvement in patients lacking focal bone lesions.

Acrometastasis to the foot: an unusual presentation of transitional cell carcinoma of the bladder.

Metastases from bladder cancer to the bones of the hands or feet are rare and usually present after the diagnosis of the primary lesion has been made. This case report describes a 76-year-old man presenting with initial signs of infection of the right foot. Subsequent bone scan revealed multiple bony metastases and hydronephrosis raising the possibility of a primary bladder tumour that was later confirmed by urine cytology and fine needle aspiration of the foot.