Australasian Consensus Statement on the Identification, Prevention, and Management of Hormonal Crises in Patients with Neuroendocrine Neoplasms Undergoing Peptide Receptor Radionuclide Therapy.

Hormonal crises are a rare but increasingly recognized phenomenon following peptide receptor radionuclide therapy (PRRT) in patients with neuroendocrine neoplasms (NENs). Due to the paucity of published studies, approaches to the identification, prevention, and management of risk factors are inconsistent between different institutions. This consensus statement aimed to provide guidance for NEN patients undergoing PRRT. Our statement has been created on the basis of clinical demand and concerns regarding the precipitation of hormonal crises. A formal literature review was conducted to identify available studies. A total of 19 Australian and New Zealand experts in the fields of medical oncology, nuclear medicine, anaesthetics, and endocrinology collaborated on this consensus statement. The main focus is on carcinoid crises. Other hormonal crises seen in patients with functional pancreatic NENs are addressed briefly. These recommendations are relevant to PRRT centres internationally and should be tailored to local experience and available resources.

High Metabolic Tumour Volume on 18-Fluorodeoxyglucose Positron Emission Tomography Predicts Poor Survival from Neuroendocrine Neoplasms.

INTRODUCTION: 18-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) avidity in neuroendocrine neoplasms (NENs) has been associated with higher-grade disease. 18F-FDG avidity and high SUVmax have been demonstrated to predict poor outcome. Quantitative metrics of 18F-FDG PET, specifically metabolic tumour volume (MTV) and total lesion glycolysis (TLG), have been shown to be prognostic factors in other malignancies, but these have not been investigated to date in NENs. METHODS: Patients with NEN undergoing 18F-FDG at Royal North Shore Hospital from 2012 to 2018 were included. Images were analysed with automated segmentation (SUV cut-off of 4) followed by contour verification by a nuclear medicine physician and manual segmentation where required. Variables collected included patient age, histological grade, MTV, TLG, and SUVmax/SUVmean. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Univariate (UV) and multivariate (MV) analyses were performed for OS and PFS for MTV and TLG separately. For UV analysis, the median MTV and TLG were used to dichotomise the cohort. MTV/TLG for NENs of different histological grade were compared using ANOVA. RESULTS: One hundred and ninety patients were included (median age 63.5, 49% female). Primary site: 42% small bowel, 32% pancreas, 15% other gastrointestinal, 6% lung, 6% other. Grade for gastroenteropancreatic NENs and bronchial NEN: G1/typical carcinoid 37%, G2/atypical carcinoid 40%, G3/large-cell/small-cell neuroendocrine carcinoma 16%, unknown 8%. Median MTV was 4.83 mL (range 0-3,161 mL) and median TLG was 29.22. Patients with high MTV had worse median OS compared to those with low MTV (29.7 months vs. not reached, HR 4.1, 95% CI 2.25-7.49, p < 0.00001). Considered as a continuous variable, MTV predicted for poorer OS on UV (p < 0.00001) and MV (p = 0.003) analyses. Whilst histological grade was significant on both UV and MV, SUVmax was significant on UV (p < 0.00001) but not MV (p = 0.76). Tumours of higher grade had higher MTV (mean MTV - G1: 39.6 mL, G2: 107 mL, G3: 337 mL; p = 0.0001 by ANOVA). CONCLUSIONS: Quantitative analysis of 18F-FDG PET in NEN is feasible. High MTV/TLG are predictors of poor prognosis in NEN. Further analyses are underway to investigate a larger cohort of NEN patients.

64Cu Treatment Planning and 67Cu Therapy with Radiolabeled [64Cu/67Cu]MeCOSar-Octreotate in Subjects with Unresectable Multifocal Meningioma: Initial Results for Human Imaging, Safety, Biodistribution, and Radiation Dosimetry.

Our aim was to report the use of 64Cu and 67Cu as a theranostic pair of radionuclides in human subjects. An additional aim was to measure whole-organ dosimetry of 64Cu and 67Cu attached to the somatostatin analog octreotate using the sarcophagine MeCOSar chelator (SARTATE) in subjects with somatostatin receptor-expressing lesions confined to the cranium, thereby permitting normal-organ dosimetry for the remainder of the body. Methods: Pretreatment PET imaging studies were performed up to 24 h after injection of [64Cu]Cu-SARTATE, and normal-organ dosimetry was estimated using OLINDA/EXM. Subsequently, the trial subjects with multifocal meningiomas were given therapeutic doses of [67Cu]Cu-SARTATE and imaged over several days using SPECT/CT. Results: Five subjects were initially recruited and imaged using PET/CT before treatment. Three of the subjects were subsequently administered 4 cycles each of [67Cu]Cu-SARTATE followed by multiple SPECT/CT imaging time points. No serious adverse events were observed, and no adverse events led to withdrawal from the study or discontinuation from treatment. The estimated mean effective dose was 3.95 × 10-2 mSv/MBq for [64Cu]Cu-SARTATE and 7.62 × 10-2 mSv/MBq for [67Cu]Cu-SARTATE. The highest estimated organ dose was in spleen, followed by kidneys, liver, adrenals, and small intestine. The matched pairing was shown by PET and SPECT intrasubject imaging to have nearly identical targeting to tumors for guiding therapy, demonstrating a potentially accurate and precise theranostic product. Conclusion: 64Cu and 67Cu show great promise as a theranostic pair of radionuclides. Further clinical studies will be required to examine the therapeutic dose required for [67Cu]Cu-SARTATE for various indications. In addition, the ability to use predictive 64Cu-based dosimetry for treatment planning with 67Cu should be further explored.

Computed tomography (CT)-defined sarcopenia and myosteatosis are prevalent in patients with neuroendocrine neoplasms (NENs) treated with peptide receptor radionuclide therapy (PRRT).

BACKGROUND/OBJECTIVES: Neuroendocrine neoplasms (NEN) may predispose patients to malnutrition. CT-defined sarcopenia and myosteatosis are common in other tumour types and recognized adverse prognostic factors. However, the prevalence and prognostic impact of sarcopenia and myosteatosis remain undetermined in NEN patients to date. METHODS: A retrospective study of NEN patients treated with peptide receptor radionuclide therapy (PRRT) at a tertiary institution from 2012 to 2017. Patients with PET/CT imaging at baseline and follow-up were included. The L3 slice of the co-localizing CT was analysed using the Alberta Protocol. Skeletal muscle cross-sectional area and muscle attenuation were measured and compared with pre-defined cut-offs. The primary endpoint was the prevalence of sarcopenia and myosteatosis according to previously published cut-offs. RESULTS: Fourty-nine patients (median age 64 (range 26-80) years) were included. The most common primary sites of tumour were the small bowel (51%) and pancreas (26%). Baseline sarcopenia was prevalent in 67% of patients and myosteatosis in 71%. Forty-five percent of patients gained weight over the course of PRRT. The presence of baseline sarcopenia was not associated with progression-free survival (20.8 mo vs. 20.7 mo, HR 0.86, p = 0.70) nor overall survival. Similarly, baseline myosteatosis (PFS 19.5 mo vs. 20.8 mo, HR 0.77, p = 0.47) was not significantly associated with survival outcomes. The mean (SD) age of those with myosteatosis was 60.8 ± 11.6 years compared to 49.7 ± 12.7 years for those without (p = 0.003). CONCLUSIONS: Body composition analysis is feasible using routinely acquired PET/CT data for patients with NEN. CT-defined sarcopenia and myosteatosis are prevalent in NEN patients, although myosteatosis is more common with increasing age. These findings were not associated with worsened overall or progression-free survival in the current study.

Pulmonary emboli imaging with (99m)Tc-labelled anti-D-dimer (DI-80B3) Fab' followed by SPECT.

OBJECTIVES: Pre-clinical experiments demonstrated that intravenous (99m)Tc labelled DI-DD-3B6/22-80B3 humanised anti-fibrin-D-dimer Fab' fragments ((99m)Tc-DI-80B3) allowed scintigraphic imaging of acute pulmonary emboli (PE). The aims of this clinical study were to determine the safety of (99m)Tc-DI-80B3 in patients with PE and evaluate the resulting scintigraphic images for the localisation of acute PE. MATERIALS/PATIENTS AND METHODS: (99m)Tc-DI-80B3 (0.5mg, 710-850MBq) was administered intravenously to subjects (n=14) with segmental or larger PE on recent contrast-enhanced helical CT scans. Thoracic SPECT scans were acquired 15 minutes, 2 hours and 4 hours afterwards. Subjects were followed for 90 days subsequently. RESULTS: There were no serious adverse events or antibody responses associated with (99m)Tc-DI-80B3 administration. Focal accumulations of (99m)Tc-DI-80B3 on the SPECT images of the thorax acquired at four hours corresponded to pulmonary emboli detected by CT. Two independent "blinded" SPECT readers identified 79% and 71% (respectively) of the right lung and 79% and 64% (respectively) of the left lung in which CT scans disclosed PE. CONCLUSIONS: (99m)Tc-DI-80B3 is well-tolerated in patients with acute PE and does not induce an immune response. (99m)Tc-DI-80B3 may offer a novel approach to imaging PE in a clinically acceptable timeframe without exposure to potentially nephrotoxic radiographic contrast agents.

Dual PET Imaging in Bronchial Neuroendocrine Neoplasms: The NETPET Score as a Prognostic Biomarker.

PET scans using 18F-FDG and somatostatin receptor imaging agents are both used in imaging of neuroendocrine neoplasms (NENs). We have suggested the "NETPET score," using uptake of both PET tracers, as a prognostic biomarker in NENs. The name NETPET score was suggested previously to capture the score's intent to summarize information from dual PET imaging in neuroendocrine tumors. We previously demonstrated the effectiveness of the NETPET score in gastroenteropancreatic NENs (GEPNENs). Its prognostic relevance in bronchial NENs remains undetermined. Methods: This is a retrospective multicenter study (2011-2018) assessing patients who had advanced bronchial NEN and who underwent both 18F-FDG and 68Ga-DOTATATE PET within 60 d of each other. The NETPET score was assigned by experienced nuclear medicine physicians and compared with other clinical data such as World Health Organization grade. The primary outcome was overall survival; NETPET score and other prognostic variables were analyzed using univariate and multivariate analyses by the Cox proportional-hazards model. Results: Thirty-eight patients were included for review. The NETPET score and histology were significantly correlated with overall survival in univariate analyses (P = 0.003, P = 0.01). On multivariate analysis, only the NETPET score remained significant (P = 0.03). The NETPET score was significantly associated with histologic grade (P = 0.006, χ2 test). Conclusion: The NETPET score is a prognostic biomarker in bronchial NENs as well as GEPNENs. Although it needs to be validated in prospective studies, it holds significant promise as a biomarker for a wide range of NENs.

Safety and tolerability of Miltuximab® - a first in human study in patients with advanced solid cancers.

OBJECTIVES: Miltuximab® is a chimeric antibody targeting Glypican-1 (GPC-1), a cell surface antigen which is overexpressed in solid cancers. Miltuximab® has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. This first in human study used Miltuximab® radiolabelled with Gallium-67 ([67Ga]Ga-DOTA-Miltuximab®). The primary study endpoint was to establish safety and tolerability of Miltuximab®. Secondary endpoints were biodistribution, tumour targeting and pharmacokinetic analysis. METHODS: Four cohorts of three patients (9 with advanced prostate cancer, 2 with pancreatic and 1 with bladder cancer) were dosed with 1 mg, ~250 MBq of [67Ga]Ga-DOTA-Miltuximab®. Cohort 1 received [67Ga]Ga-DOTA-Miltuximab® alone, while cohorts 2-4 were pre-infused with increasing doses (3.5, 11.5 and 24 mg, respectively) of unlabelled Miltuximab®-DOTA 1 hour prior to [67Ga]Ga-DOTA-Miltuximab®. Safety and tolerability were assessed by clinical and standard laboratory assessments. Patients underwent whole body gamma-camera scans and SPECT/CT scans up to 144 h post-infusion. Total organ radiation exposure was determined by dosimetry of whole-body gamma scans. RESULTS: The dosing regimen was well tolerated, with no drug-related adverse events observed. Liver and spleen uptake of [67Ga]Ga-DOTA-Miltuximab® was observed. Liver uptake was reduced by pre-infusion of unlabelled Miltuximab®-DOTA. Dosimetry analysis showed a favorable exposure profile. [67Ga]Ga-DOTA-Miltuximab® targeting to tumour sites was observed in two prostate cancer patients who had failed enzalutamide treatment. Higher doses of unlabelled antibody achieved lower liver uptake and increased antibody serum half life. CONCLUSIONS: This study is the first in human for Miltuximab® a first in class antibody targeting GPC-1. The trial met its primary endpoint of safety, demonstrating its potential as a safe and tolerable monoclonal antibody. This safety data, together with targeting to tumour lesions and biodistribution information supports the further clinical development of Miltuximab® as a theranostic agent in a planned Phase I human trial.

The utility of metaiodobenzylguanidine single photon emission computed tomography/computed tomography (MIBG SPECT/CT) for the diagnosis of pheochromocytoma.

BACKGROUND: The enhancement of metaiodobenzylguanidine single photon emission computed tomography (MIBG SPECT) imaging through the addition of CT images fused with SPECT data (coregistered MIBG SPECT/CT imaging) is new technology that allows direct correlation of anatomical and functional information. We hypothesized that MIBG SPECT/CT imaging would provide additional information and improve diagnostic confidence for the radiological localization of a pheochromocytoma, in particular for patients at high risk of multifocal or recurrent disease. METHODS: A retrospective study of all patients investigated by MIBG SPECT/CT at our institution from 2006 to 2008 for a suspected pheochromocytoma was performed. Each case was compared with conventional radiological investigations to determine whether MIBG SPECT/CT was able to improve diagnostic confidence and provide additional diagnostic information compared with conventional imaging alone. RESULTS: Twenty-two patients had MIBG SPECT/CT imaging for a suspected pheochromocytoma. Fourteen patients had positive MIBG SPECT/CT imaging results correlating with imaging by CT or magnetic resonance imaging in all cases. In six cases, MIBG SPECT/CT provided additional information that altered the original radiological diagnosis. Five patients with a pheochromocytoma-associated germline mutation had multifocal disease excluded by MIBG SPECT/CT. Patients without a germline mutation that had positive biochemistry and a solitary lesion with conventional imaging had no diagnostic improvement with MIBG SPECT/CT imaging. CONCLUSIONS: MIBG SPECT/CT fusion imaging is a sensitive and specific radiological imaging tool for patients suspected to have pheochromocytoma. The particular strengths of MIBG SPECT/CT are detection of local recurrence, small extra-adrenal pheochromocytomas, multifocal tumors, or the presence of metastatic disease.

Preoperative body composition is influenced by the stage of operable pancreatic adenocarcinoma but does not predict survival after Whipple's procedure.

OBJECTIVES: Cachexia is common in pancreatic cancer and may have an influence on longterm survival but few studies have investigated this in patients with operable tumours. Therefore, this study was carried out to document body composition status in patients with pancreatic adenocarcinoma (PCa) presenting for a Whipple's procedure (WP) and to relate the findings to histopathology and longterm survival. METHODS: Body composition was measured 1 day before a WP for ductal PCa in 36 patients (15 men, 21 women) aged 41-81 years. Results for total body nitrogen (TBN), nitrogen index (NI), total body water (TBW), fat mass (FM) and total body potassium (TBK) were compared with results in 73 age- and sex-matched controls. Patients' survival and details from histopathology synoptic reports were documented. RESULTS: Patients undergoing WPs had low TBK values (P < 0.001) and females had lower body fat (P = 0.007) compared with controls. Five of 36 presented with significant protein deficiency, but this was not associated with a prolonged length of stay or reduced survival. The 12 patients who had involved surgical margins had larger tumours and reduced weight (P = 0.015), FM (P = 0.001), TBN (P = 0.045), TBK (P = 0.014) and survival (P = 0.036). However, multivariate Cox's regression analysis only included FM along with vascular invasion and margin status as independent predictors of survival. CONCLUSIONS: PCa patients undergoing a WP have reduced body fat and TBK compared with community controls while those with stage III tumours had greater deficits of fat, TBK and protein stores. However, preoperative body composition was a poor predictor of postoperative survival after pathological data were considered.

A Brief History of Lung Ventilation and Perfusion Imaging Over the 50-Year Tenure of the Editors of Seminars in Nuclear Medicine.

The ventilation/perfusion lung scan has been in continuous use for approximately half a century, the same lifetime as Seminars in Nuclear Medicine. Remarkably, the founding Editors-in-Chief have continued to guide the journal over this entire period. In this Feschrift issue celebrating their enormous contribution, we review the history of the lung scan, its highs and lows, the transition from planar to SPECT/CT V/Q scans, and the future that is in store in this age of multimodality functional imaging. We concur with the published view of one of the retiring editors (LMF) that V/Q scintigraphy is indeed alive and well and has a definite future in clinical medicine.

Routine Early 68Ga-DOTATATE Positron Emission Tomography Has Low Yield After Resection of Appendiceal Neuroendocrine Neoplasms.

OBJECTIVES: Appendiceal neuroendocrine neoplasms (appNEN) generally carry a low recurrence risk. Ga-DOTATATE positron emission tomography (DOTA PET) is increasingly used as it is more sensitive than cross-sectional imaging. We hypothesize that early DOTA PET is unlikely to detect recurrent disease in patients with low-risk resected appNEN because of the delayed pattern of recurrence. METHODS: Retrospective study (dual review) of patients undergoing DOTA PET 0 to 18 months after resected appNEN. The primary outcome was the proportion of scans demonstrating residual disease. RESULTS: Forty-one patients were included (median age, 29 years; 63% female), most with small, low-grade appNEN. No scans (0%) showed residual/distant disease. Eight (20%) of 41 scans showed indeterminate findings requiring follow-up. Five (12%) scans were recommended for follow-up with modalities other than DOTA PET (vertebra, 3; thyroid; bone, 1 each). Three (7%) were recommended for follow-up with DOTA PET (all with indeterminate abdominal uptake). These 3 patients had no recurrent disease on follow-up. CONCLUSIONS: The Ga-DOTATATE PET is of no value when performed in the first 18 months after resected appNEN. Although 20% of scans showed indeterminate findings, more than half did not require repeat DOTA PET. Despite advantages over cross-sectional imaging, DOTA PET is not recommended in staging after completely resected appNEN.

A clinical comparison between traditional planar V/Q images and planar images generated from SPECT V/Q scintigraphy.

PURPOSE: To compare interpretation of traditional planar ventilation-perfusion lung scan images with planar images reformatted from single photon emission computed tomography (SPECT) data using two different techniques. METHODS: Planar and SPECT ventilation-perfusion (V/Q) data were acquired from 50 patients referred with suspected pulmonary embolism. In addition to traditional six-view planar images, six-view planar images were also generated from SPECT data using two methodologies: an angular summing technique (angular summed planar images) and a forward projection technique (reprojected planar images). Three experienced nuclear medicine clinicians reviewed the images in a blinded, randomized fashion. Results were analysed by comparing the two reprojected techniques with the traditional true planar scans, examining for differences in the defects seen (number, type and confidence), and the impact on final clinical interpretation. RESULTS: Compared with true planar scintigraphy, angular summed images demonstrated fewer mismatched defects (P<0.0001), while the reprojected planar images had more matched defects (P=0.013). In addition, there was a significant change in the clinical interpretation of the angular summed planar images resulting in clinicians perceiving a decreased likelihood of pulmonary embolism (P<0.016). No such difference in interpretation was observed for the reprojected planar images. CONCLUSIONS: Angular summed planar images result in a perceived decreased likelihood of pulmonary embolism compared with true planar images. In contrast, while reprojected planar images result in an increased number of matched defects compared to true planar scans, there was no change in the clinical interpretation. Caution should be exercised when interpreting SPECT derived angular summed planar images in isolation.

Comparison of pinhole and SPECT 99mTc-MIBI imaging in primary hyperparathyroidism.

OBJECTIVE: This study aims to compare dual tracer, dual phase pinhole technetium-99m labelled 2-methoxyisobutylisonitrile (Tc-MIBI) imaging (including oblique imaging), with single photon emission computed tomography (SPECT) and dual phase planar Tc-MIBI images, and combined SPECT, dual phase planar Tc-MIBI images and anterior pinhole thyroid images for the localization of parathyroid adenomas in the neck in primary hyperparathyroidism. METHODS: Sixty-two patients underwent Tc-MIBI dual phase, anterior and anterior oblique pinhole images of the neck, anterior planar images of the neck and chest and early phase neck/chest SPECT followed by [Tc] pertechnetate anterior and anterior oblique pinhole thyroid images. Images were reviewed by consensus in three combinations - dual phase anterior and anterior oblique pinhole Tc-MIBI images and pinhole thyroid images; SPECT and dual phase planar Tc-MIBI images and combined SPECT, dual phase planar Tc-MIBI images and anterior pinhole thyroid images. RESULTS: For 52 parathyroid adenomas in 50 patients, the sensitivity of dual phase anterior and anterior oblique pinhole Tc-images and pinhole thyroid images was 81%. Significantly lower sensitivities were observed with SPECT and dual phase planar Tc-MIBI images (54%, P=0.0005) and combined SPECT, dual phase planar Tc-MIBI images and anterior pinhole thyroid images (65%, P=0.0209). The positive predictive value for all imaging combinations was 88-92%. CONCLUSION: Dual phase anterior and anterior oblique pinhole Tc-MIBI images and pinhole thyroid images are significantly more sensitive than imaging combinations that included SPECT and remains the optimal imaging protocol for the localization of parathyroid adenomas in the neck in primary hyperparathyroidism.

Objective analysis of whole lung and lobar ventilation/perfusion relationships in pulmonary embolism.

PURPOSE: Lung scintigraphy using single photon emission computed tomography (SPECT) allows accurate regional measurement of the ventilation/perfusion (V/Q) relationship. Objective V/Q analysis has been shown to be useful in the diagnosis of pulmonary embolism (PE). By using anatomical information provided by co-registered computed tomography, we describe methodology for determining the extent of V/Q heterogeneity at a lobar level. We investigate this methodology using simulated data, and demonstrate its potential application in the clinical setting of PE. METHODS: Data representing an incremental perfusion defect involving the right lung, together with an unaffected ventilation dataset, were modelled using Monte Carlo simulation. For each increase in the size of the perfusion defect, the whole lung V/Q relationship was objectively determined. In addition, using an image mask of the pulmonary lobes, lobar V/Q relationships were also determined. V/Q heterogeneity was characterized using the log(10) standard deviation of the V/Q ratio (log SDVQR), ventilation (log SDV) and perfusion (log SDQ) distributions. Finally, this methodology was explored in clinical cases. RESULTS: As an increasing number of segments were involved by perfusion defects, there was a progressive increase in all objective parameters of V/Q heterogeneity. The relative change was greatest for log SDV. Analysis of both the simulated and clinical studies demonstrated sensitive changes in the lobar V/Q profiles to the presence of PE. CONCLUSIONS: Segmentation and analysis of SPECT ventilation-perfusion scintigraphy at a lobar level can be used to quantify regional V/Q relationships. This objective methodology is sensitive to the presence of PE, and may be useful in a clinical setting.

Generation of planar images from lung ventilation/perfusion SPECT.

OBJECTIVE: To develop a method of producing lung ventilation and perfusion (V/Q) planar images using forward projection of reconstructed single-photon emission computed tomography (SPECT) images through approximate attenuation (micro) maps generated from the lung emission scans alone, as transmission-based micro maps may not be routinely available. METHODS: Synthetic micro maps are derived from (99m)Tc photopeak and "scatter" windows for the attenuation correction of the SPECT images. The attenuation-corrected SPECT images are forward projected at appropriate angles to give the equivalent of planar images. This method allows high-count planar images, as well as the SPECT images, to be produced from a single SPECT acquisition. In addition, isolated "single lung" views of lateral and medial projections without "shine-through" from the contra-lateral lung, which have not been available previously, can be formed. RESULTS: Comparison of reprojected images produced from CT-derived or synthetic micro maps displayed similar detail and radiopharmaceutical distribution. In a blinded comparison of "true" planar images with those from reprojecting the SPECT data using the synthetic micro maps, no difference in mismatched defect detection was found, and hence it was confirmed that the reprojected planar images could replace true planar images with no loss in planar diagnostic sensitivity. CONCLUSIONS: The reprojected planar images provide high-count, high-quality images, which are comparable with conventional 2D images.

Utilizing 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) to define suspected nonenhancing tumor for radiation therapy planning of glioblastoma.

AIM: The authors sought to evaluate the impact of 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) on radiation therapy planning for patients diagnosed with glioblastoma (GBM) and the presence of suspected nonenhancing tumors compared with standard magnetic resonance imaging (MRI). METHODS AND MATERIALS: Patients with GBM and contrast-enhanced MRI scans showing regions suspicious of nonenhancing tumor underwent postoperative FET-PET before commencing radiation therapy. Two clinical target volumes (CTVs) were created using pre- and postoperative MRI: MRI fluid-attenuated inversion recovery (FLAIR) sequences (CTVFLAIR) and MRI contrast sequences with an expansion on the surgical cavity (CTVSx). FET-PET was used to create biological tumor volumes (BTVs) by encompassing FET-avid regions, forming BTVFLAIR and BTVSx. Volumetric analyses were conducted between CTVs and respective BTVs using Wilcoxon signed-rank tests. The volume increase with addition of FET was analyzed with respect to BTVFLAIR and BTVSx. Presence of focal gadolinium contrast enhancement within previously nonenhancing tumor or within the FET-avid region was noted on MRI scans at 1 and 3 months after radiation therapy. RESULTS: Twenty-six patients were identified retrospectively from our database, of whom 24 had demonstrable FET uptake. The median CTVFLAIR, CTVSx, BTVFLAIR, and BTVSx were 57.1 mL (range, 1.1-217.4), 83.6 mL (range, 27.2-275.8), 62.8 mL (range, 1.1-307.3), and 94.7 mL (range, 27.2-285.5), respectively. When FET-PET was used, there was a mean increase in volume of 26.8% from CTVFLAIR to BTVFLAIR and 20.6% from CTVSx to BTVSx. A statistically significant difference was noted on Wilcoxon signed-rank test when assessing volumetric change between CTVFLAIR and BTVFLAIR (P < .0001) and CTVSx and BTVSx (P < .0001). Six of 24 patients (25%) with FET avidity before radiation therapy showed focal gadolinium enhancement within the radiation therapy portal. CONCLUSIONS: FET-PET may help improve delineation of GBM in cases with a suspected nonenhancing component. This may result in improved radiation therapy target delineation and reduce the risk of potential geographical miss. SUMMARY: We investigated the impact of 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) on radiation therapy planning for patients diagnosed with glioblastoma (GBM) and a suspected nonenhancing tumor compared with standard magnetic resonance imaging. We performed volumetric analyses between clinical target volumes and respective biological target volumes using Wilcoxon signed-rank tests. FET-PET may help improve delineation of GBM in cases with a suspected nonenhancing component and reduce the risk of potential geographical miss.

FET PET in the evaluation of indeterminate brain lesions on MRI: Differentiating glioma from other non-neoplastic causes - A pilot study.

We aimed to determine the utility of FET PET in the management of indeterminate CNS lesions found on MRI. We performed a retrospective analysis of patients with FET PET at a single tertiary institution from 2011 to 2015. FET PET images were processed using usual methods and measurements taken including SUVmax, TBRmax, and analysis of dynamic series where available (Kipeak, Vdpeak, as well as tumor:background ratio for these variables). Correlation studies were performed using ANOVA between cohorts of high-grade histology, low-grade histology, and benign histology/stable on observation. Thirty-five patients were included, of whom 34 were suitable for analysis with median follow-up of 5 months. The positive predictive value of FET PET in this cohort was 83.3%. FET SUVmax differentiated between patients with high-grade (mean SUV 3.38, 95% CI 2.21-4.55), low-grade (1.88, 95% CI 1.33-2.43) and benign/observation (1.42, 95% CI 1.13-1.71) cohorts (p = 0.0003). Similarly, tumour to brain ratio was significant (p < 0.0001). Kipeak distinguished between high grade and observation cohorts (p = 0.036), as did KiTBR (p = 0.025). Vd peak was not significantly different in these two cohorts (p = 0.057) but Vd TBR was (p = 0.041). In conclusion, FET PET demonstrated a high positive predictive value for glioma in patients with indeterminate brain lesions on MRI. The combination of negative FET and negative FDG PET scans may predict an indolent clinical course. Confirmatory trials are needed to establish the potential value of FET PET in guiding surgical management in this cohort.

The Impact of 68Ga-PSMA PET/CT on Management Intent in Prostate Cancer: Results of an Australian Prospective Multicenter Study.

68Ga-PSMA PET/CT scanning has been shown to be more sensitive than conventional imaging techniques in patients with prostate cancer. This prospective Australian multicenter study assessed whether 68Ga-PSMA PET/CT imaging affects management intent in patients with primary or recurrent prostate cancer. Methods: Before undertaking 68Ga-PSMA PET imaging, referring medical specialists completed a questionnaire detailing relevant demographic and clinical data as well as their proposed management plan. A separate follow-up questionnaire was completed after the 68Ga-PSMA PET/CT scan results were available to determine whether the management plan would change. Results: A total of 431 patients with prostate cancer from 4 Australian centers had pre- and post-68Ga-PSMA management plans completed. Scans were obtained for primary staging of intermediate- and high-risk disease in 25% of patients and for restaging/biochemical recurrence in 75% of patients. Overall, 68Ga-PSMA PET/CT scanning led to a change in planned management in 51% of patients. The impact was greater in the group of patients with biochemical failure after definitive surgery or radiation treatment (62% change in management intent) than in patients undergoing primary staging (21% change). Imaging with 68Ga-PSMA PET/CT revealed unsuspected disease in the prostate bed in 27% of patients, locoregional lymph nodes in 39%, and distant metastatic disease in 16%. Conclusion:68Ga-PSMA PET/CT scans detect previously unsuspected disease and may influence planned clinical management in a high proportion of patients with prostate cancer. The impact was greater in patients with biochemical recurrence. These results demonstrate the potential clinical value of 68Ga-PSMA PET/CT in management of prostate cancer.