Role of 18F-choline and 18F-fluorodeoxyglucose positron emission tomography in combination with magnetic resonance imaging in brachytherapy planning for locally advanced cervical cancer: A pilot study.

Background and purpose: This pilot study aims to describe the advantages of combining metabolic and anatomic imaging modalities in brachytherapy (BT) planning for locally advanced cervical cancer (LACC) and to evaluate the supplementary value of Fluoro(F)-Choline positron emission tomography/computed tomography (PET/CT) in comparison to 18F-fluorodeoxyglucose (FDG) in this setting. Materials and methods: A prospective cohort of six patients with LACC was included in this study. Each patient underwent BT planning CT scan, magnetic resonance imaging (MRI), and both FDG and F-Choline PET/CT scans on the same day, with BT applicators in place. Patients were treated according to the standard of care. Metabolic target volumes (TV) were generated retrospectively and compared with the anatomic volumes using Dice coefficients and absolute volume comparison. Results: The threshold at which the metabolic and anatomic volumes were the most concordant was found to be 35% maximum standardized uptake value (SUV max) for both PET/CT scans. Amongst the six patients in this cohort, three in the FDG cohort and four in the F-Choline cohort were found to have more than ten percent ratio of excess (increase) in their MRI gross tumor volumes (GTV) when incorporating the metabolic information from the PET/CT scans. However, no significant changes were needed in the high risk-clinical target volumes (CTVHR) for both PET tracers. Conclusions: FDG and F-Choline PET/CT scans can substantially modify the BT GTV on MRI, without affecting the CTVHR. F-Choline is potentially more informative than FDG in assessing residual TV, particularly in cases with significant post-radiation inflammatory changes.

Adaptive Fluorodeoxyglucose-Positron Emission Tomography Based Chemotherapy Selection for Metastatic Non-small Cell Lung Cancer.

Objectives The change in tumor fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) scan after one cycle of platinum-based chemotherapy has been shown to predict progression-free and overall survival (PFS and OS) among advanced non-small cell lung cancer (NSCLC) patients. Using early FDG-PET response to determine subsequent chemotherapy, we aim to evaluate the role that adaptive chemotherapy regimens have on later CT response, PFS, and OS in patients with advanced NSCLC. Materials and Methods Chemotherapy-naïve patients with metastatic NSCLC received carboplatin and paclitaxel (CP) on day one and repeated FDG-PET on day 18. PET-responding patients continued CP chemotherapy for a total of four cycles. PET non-responders were switched to alternate docetaxel and gemcitabine (DG) for three additional cycles. The primary outcome was the CT Response Evaluation Criteria in Solid Tumors (RECIST 1.0) response. Secondary endpoints included PFS and OS. Results  Forty-six patients initiated treatment with chemotherapy on trial and were evaluable by PET/CT. Of these, 19 (41%) met the FDG-PET criteria for the response after a single cycle of CP. Only one non-responding patient had a CT response. Despite the lack of CT response in the DG arm, no trend for worse PFS or OS was seen between the two arms. Conclusions This work demonstrates that changing chemotherapy in the event of non-response by PET did not lead to improved CT RECIST response. However, non-responding patients who switched chemotherapy had similar PFS and OS to those who responded by PET and continued the same regimen.

Physiologic colonic uptake of 18F-FDG on PET/CT is associated with clinical response and gut microbiome composition in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICI) represent the backbone treatment for advanced non-small cell lung cancer (NSCLC). Emerging data suggest that increased gut microbiome diversity is associated with favorable response to ICI and that antibiotic-induced dysbiosis is associated with deleterious outcomes. 18F-FDG physiologic colonic uptake on PET/CT increases following treatment with antibiotics (ATB) and could act as a surrogate marker for microbiome composition and predict prognosis. The aim of this study was to determine if 18F-FDG physiologic colonic uptake prior to ICI initiation correlates with gut microbiome profiling and clinical outcomes in patients with advanced NSCLC. METHODS: Seventy-one patients with advanced NSCLC who underwent a PET/CT prior to ICI were identified. Blinded colonic contouring was performed for each colon segment and patients were stratified according to the median of the average colon SUVmax as well as for each segment in low vs. high SUVmax groups. Response rate, progression-free survival (PFS), and overall survival (OS) were compared in the low vs. high SUVmax groups. Gut microbiome composition was analyzed for 23 patients using metagenomics sequencing. RESULTS: The high colon SUVmax group had a higher proportion of non-responders (p = 0.033) and significantly shorter PFS (4.1 vs. 11.3 months, HR 1.94, 95% CI 1.11-3.41, p = 0.005). High caecum SUVmax correlated with numerically shorter OS (10.8 vs. 27.6 months, HR 1.85, 95% CI 0.97-3.53, p = 0.058). Metagenomics sequencing revealed distinctive microbiome populations in each group. Patients with low caecum SUVmax had higher microbiome diversity (p = 0.046) and were enriched with Bifidobacteriaceae, Lachnospiraceae, and Bacteroidaceae. CONCLUSIONS: Lower colon physiologic 18F-FDG uptake on PET/CT prior to ICI initiation was associated with better clinical outcomes and higher gut microbiome diversity in patients with advanced NSCLC. Here, we propose that 18F-FDG physiologic colonic uptake on PET/CT could serve as a potential novel marker of gut microbiome composition and may predict clinical outcomes in this population.

The Peritoneum: What Nuclear Radiologists Need to Know.

The peritoneum is the largest and most complex serous membrane in the human body. The peritoneal membrane is composed of a layer of mesothelium supported by a thin layer of connective tissue. The peritoneum is one continuous sheet, forming two layers and a potential space between them - the peritoneal cavity- which is subdivided into multiple communicating spaces containing small amount of serous fluid that facilitates frictionless movement of mobile intraabdominal viscera. Peritoneum also contributes to fluid exchange mechanism and plays a role in immune response. The peritoneum is subject to many neoplastic and non-neoplastic processes including infections, trauma, developmental and inflammatory processes. Different Nuclear Medicine imaging techniques can be used to diagnose peritoneal diseases, most of these techniques can be customized depending on the clinical scenario and expected findings. Peritoneal scintigraphy can detect abnormal peritoneal communication or compartmentalization. Several nuclear medicine techniques can help characterize intraperitoneal fluid collections and differentiate sterile from infected fluid. PET imaging plays an important role in imaging of different neoplastic and non-neoplastic peritoneal pathologies. Nuclear radiologists need to be familiar with peritoneal anatomy and pathology to interpret peritoneal findings in dedicated peritoneal nuclear medicine imaging studies, as part of more general nuclear medicine scans, or on CT or MRI component of hybrid imaging studies. The purpose of this article is to review the normal peritoneal anatomy, various pathologic processes involving the peritoneum, and different nuclear medicine and hybrid imaging techniques that can help detect, characterize, and follow up peritoneal pathology.

Practical considerations for establishing dead-time corrections in quantitative SPECT imaging.

Quantitative SPECT studies require specific information about the equipment being used. Particularly in the context of therapeutic studies, the effect of dead-time can be significant and must be quantified. We explored different techniques for measuring the dead-time constant and applying dead-time corrections to the data. METHOD: The dead-time constant was measured on four similar SPECT/CT systems by following the response of the system to a uniform phantom initially containing 17 GBq of Lu-177 over a period of 23 days. It was then calculated using the two-source method with 1 332 MBq of Tc-99 m. The dead-time constant found was used to correct SPECT/CT phantom images either applying the correction by projection or globally on the image. RESULTS: Both methods of calculating the dead-time constant produced equivalent results. However, the dead-time constant varied by as much as 8% between machines of the same model and manufacturer. Correcting for dead-time by projection rather than globally produced slightly more precise results (0.94% error rather than 2.59% error). The benefit of this correction technique will be dependent on the level of asymmetry in the patient as well as the magnitude of the dead-time correction effect. CONCLUSION: quantification of the dead-time of a system can be performed quickly using the two-source method and any radioisotope. However, it is important to perform this measurement on every system being used. In vastly asymmetric images with high dead-time correction, correcting for dead-time by projection can be pertinent, increasing the precision of dosimetry calculations by several percent. However this additional gain may be within the error of SUV measurements for many clinical acquisitions.

Simplified and robust one-step radiosynthesis of [18 F]DCFPyL via direct radiofluorination and cartridge-based purification.

[18 F]DCFPyL is a clinical-stage PET radiotracer used to image prostate cancer. This report details the efficient production of [18 F]DCFPyL using single-step direct radiofluorination, without the use of carboxylic acid-protecting groups. Radiolabeling reaction optimization studies revealed an inverse correlation between the amount of precursor used and the radiochemical yield. This simplified approach enabled automated preparation of [18 F]DCFPyL within 28 minutes using HPLC purification (26% ± 6%, at EOS, n = 4), which was then scaled up for large-batch production to generate 1.46 ± 0.23 Ci of [18 F]DCFPyL at EOS (n = 7) in high molar activity (37 933 ± 4158 mCi/µmol, 1403 ± 153 GBq/µmol, at EOS, n = 7). Further, this work enabled the development of [18 F]DCFPyL production in 21 minutes using an easy cartridge-based purification (25% ± 9% radiochemical yield, at EOS, n = 3).

Reproducibility of Lobar Perfusion and Ventilation Quantification Using SPECT/CT Segmentation Software in Lung Cancer Patients.

Planar perfusion scintigraphy with 99mTc-labeled macroaggregated albumin is often used for pretherapy quantification of regional lung perfusion in lung cancer patients, particularly those with poor respiratory function. However, subdividing lung parenchyma into rectangular regions of interest, as done on planar images, is a poor reflection of true lobar anatomy. New tridimensional methods using SPECT and SPECT/CT have been introduced, including semiautomatic lung segmentation software. The present study evaluated inter- and intraobserver agreement on quantification using SPECT/CT software and compared the results for regional lung contribution obtained with SPECT/CT and planar scintigraphy. Methods: Thirty lung cancer patients underwent ventilation-perfusion scintigraphy with 99mTc-macroaggregated albumin and 99mTc-Technegas. The regional lung contribution to perfusion and ventilation was measured on both planar scintigraphy and SPECT/CT using semiautomatic lung segmentation software by 2 observers. Interobserver and intraobserver agreement for the SPECT/CT software was assessed using the intraclass correlation coefficient, Bland-Altman plots, and absolute differences in measurements. Measurements from planar and tridimensional methods were compared using the paired-sample t test and mean absolute differences. Results: Intraclass correlation coefficients were in the excellent range (above 0.9) for both interobserver and intraobserver agreement using the SPECT/CT software. Bland-Altman analyses showed very narrow limits of agreement. Absolute differences were below 2.0% in 96% of both interobserver and intraobserver measurements. There was a statistically significant difference between planar and SPECT/CT methods (P < 0.001) for quantification of perfusion and ventilation for all right lung lobes, with a maximal mean absolute difference of 20.7% for the right middle lobe. There was no statistically significant difference in quantification of perfusion and ventilation for the left lung lobes using either method; however, absolute differences reached 12.0%. The total right and left lung contributions were similar for the two methods, with a mean difference of 1.2% for perfusion and 2.0% for ventilation. Conclusion: Quantification of regional lung perfusion and ventilation using SPECT/CT-based lung segmentation software is highly reproducible. This tridimensional method yields statistically significant differences in measurements for right lung lobes when compared with planar scintigraphy. We recommend that SPECT/CT-based quantification be used for all lung cancer patients undergoing pretherapy evaluation of regional lung function.

The relative value of 18F-FDG PET interpretation criteria in generating a probabilistic approach for characterization of pulmonary nodules.

PURPOSE: The evaluation of pulmonary nodules constitutes a large part of PET-CT studies. In this study, we aimed to evaluate the different interpretation criteria in F-fluorodeoxyglucose PET attenuation-corrected and non-attenuation-corrected studies as individual predictors of malignancy in order to propose a useful combination of criteria that can be used in daily practice to classify nodules appropriately. PATIENTS AND METHODS: We performed a historical prospective survey of all consecutive patients referred to our service for the initial assessment of pulmonary nodules and sought the final characterization of these nodules either from tissue sampling or from radiological and clinical follow-up. RESULTS: A total of 104 nodules from 82 patients were included, with a prevalence of malignancy of 53%. Absence of uptake on non-attenuation-corrected studies was found to be the best predictive criterion for benignancy, with a negative predictive value of 97%, and the highest relative risk for malignancy, with a value of 20.9. Uptake higher than that of the mediastinum on attenuation-corrected images was found to be the best criterion for predicting malignancy, with a positive predictive value of 89% and a sensitivity of 73%, which is slightly better than the use of a maximal standardized uptake value cutoff of 3.0. By combining our best negative and positive criteria, we were able to classify 71% (74/104) of the lung nodules with a high level of confidence. More specifically, these two criteria allowed the correct classification of 72% (40/55) of malignant nodules and 57% (28/49) of benign nodules. The 30 remaining nodules were equally distributed in terms of malignancy and had similar characteristics on both PET and CT images. CONCLUSION: A probabilistic approach to pulmonary nodule characterization may help the reading physician to appropriately classify lung nodules into useful categories for the treating physician, moving away from nonstandardized reporting terms.

Tumor 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) uptake by PET correlates with thymidine kinase 1 expression: static and kinetic analysis of (18)F-FLT PET studies in lung tumors.

UNLABELLED: We report the first, to our knowledge, findings describing the relationships between both static and dynamic analysis parameters of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET and the expression of the proliferation marker Ki-67, and the protein expression and enzymatic activity of thymidine kinase-1 (TK1) in surgically resected lung lesions. METHODS: Static and dynamic analyses (4 rate constants and 2 compartments) of (18)F-FLT PET images were performed in a cohort of 25 prospectively accrued, clinically suspected lung cancer patients before surgical resection (1 lesion was found to be benign after surgery). The maximal and overall averaged expression of Ki-67 and TK1 were determined by semiquantitative analysis of immunohistochemical staining. TK1 enzymatic activity was determined by in vitro assay of extracts prepared from flash-frozen samples of the same tumors. RESULTS: Static (18)F-FLT uptake (partial-volume-corrected maximum-pixel standardized uptake value from 60- to 90-min summed dynamic data) was significantly correlated with the overall (ρ = 0.57, P = 0.006) and maximal (ρ = 0.69, P < 0.001) immunohistochemical expressions of Ki-67 and TK1 (overall expression: ρ = 0.65, P = 0.001; maximal expression: ρ = 0.68, P < 0.001) but not with TK1 enzymatic activity (ρ = 0.34, P = 0.146). TK1 activity was significantly correlated with TK1 protein expression only when immunohistochemistry was scored for maximal expression (ρ = 0.52, P = 0.029). Dynamic analysis of (18)F-FLT PET revealed correlations between the flux constant (K(FLT)) and both overall (ρ = 0.53, P = 0.014) and maximal (ρ = 0.50, P = 0.020) TK1 protein expression. K(FLT) was also associated with both overall (ρ = 0.59, P = 0.005) and maximal (ρ = 0.63, P = 0.002) Ki-67 expression. We observed no significant correlations between TK1 enzyme activity and K(FLT). In addition, no significant relationships were found between TK1 expression, TK1 activity, or Ki-67 expression and any of the compartmental rate constants. CONCLUSION: The absence of observable correlations of the imaging parameters with TK1 activity suggests that (18)F-FLT uptake and retention within cells may be complicated by a variety of still undetermined factors in addition to TK1 enzymatic activity.