Delineation and agreement of FET PET biological volumes in glioblastoma: results of the nuclear medicine credentialing program from the prospective, multi-centre trial evaluating FET PET In Glioblastoma (FIG) study-TROG 18.06.

PURPOSE: The O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation. METHODS: Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (n = 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBRmax), dynamic analysis (time activity curve [TAC] type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBRmax/TBRmean) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient [DSC]) and boundary agreement (Hausdorff distance [HD], mean absolute surface distance [MASD]). RESULTS: Data was accrued from 21 NMPs (10 centres, n ≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBRmax, and TBRmean were 21.53% (12.00-30.10%), 5.89% (5.01-6.68%), and 5.01% (3.37-6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63-0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement. CONCLUSION: The FIG study credentialing program has increased expertise across study sites. TBRmax and TBRmean were robust, with considerable variability in BTV delineation and image interpretation observed.

Quantifying the effects of absorbed dose from radioembolisation on healthy liver function with [99mTc]TcMebrofenin.

PURPOSE: To quantify the effects of absorbed radiation dose on healthy liver parenchyma following radioembolisation (RE) using [99mTc]TcMebrofenin to analyse both global and regional liver function. METHODS: Patients having RE to treat hepatic disease underwent a [99mTc]TcMebrofenin hepatobilliary scintigraphy (HBS) study at both baseline and 8 weeks following treatment. Changes in global liver uptake rate were compared with healthy liver absorbed dose measures derived from the post-treatment 90Y PET/CT, including average dose, minimum dose to 70% of the volume (D70) and volume receiving at least 50 Gy (V50). Changes in functional burden associated with treatment and spared liver volumes in patients receiving lobar RE were also assessed, as were changes experienced by regional volumes corresponding to various dose ranges. Standard liver function pathology tests (LFTs) (bilirubin, albumin, ALP, AST, ALT and GGT) were examined for changes between baseline and post-treatment. RESULTS: Thirty-five patients were included in the study, of which, 9 had lobar treatment. A significant linear correlation was found between both baseline global liver uptake rate (negative) and D70 with change in global liver uptake rate. Patients undergoing lobar treatments demonstrated a shift in functional burden, and a significant difference was seen between the mean dose corresponding to liver volumes that increased their functional burden (9 Gy) and those that decreased their functional burden (35 Gy). No baseline LFTs predicted a decrease in global liver function; however, D70 demonstrated a linear correlation with changes in bilirubin and GGT. CONCLUSIONS: Given the significant negative relationship between baseline and change in global liver uptake rate, baseline HBS studies should not be used alone to disqualify patients considered for RE. In terms of treatment planning and evaluation, D70 may be the most appropriate metric of dose, with values greater than 15 Gy indicative of a likely drop in global liver function. The evidence of increasing functional burden in spared liver volumes suggests that patients at risk of complications could benefit from a lobar approach to treatment.

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.

Is 67gallium dead? A retrospective review of 67gallium imaging in a single tertiary referral centre.

BACKGROUND: [67Ga]Ga-citrate scanning has been used to investigate patients with known or suspected infection for over 50 years, continuing to maintain a clinical niche in many centres. The introduction of single photon emission tomography/computed tomography (SPECT/CT) in addition to planar imaging has improved the specificity of diagnosis. AIM: To examine the experience of modern [67Ga]Ga-citrate scanning in a single tertiary referral centre, considering the diagnostic yield of the study. METHODS: A retrospective audit was undertaken of 100 consecutive [67Ga]Ga-citrate scans at Royal North Shore Hospital, Sydney. Recorded information included patient demographics, clinical information/history, and primary and secondary diagnoses. Subgroup analyses included patients with a confirmed diagnosis of infection or a suspected diagnosis of infection. RESULTS: The median age of patients was 68.5 years. Totally, 39/100 patients undergoing [67Ga]Ga-citrate scanning presented with a confirmed site of infection, with 2/6 patients with infective endocarditis and 5/12 patients with bacteraemia diagnosed with an additional, previously unknown, site of active infection (compared to 1/21 patients without documented bacteraemia). 61/100 patients did not have a confirmed site of infection before [67Ga]Ga-citrate scan (as per clinical history). 34/61 of these patients had a positive scan result for active infection/inflammation. Of 20 patients with a positive blood culture but no suspected site of infection, the source was identified in 9. CONCLUSION: [67Ga]Ga-citrate has diagnostic value in the evaluation of complex patients with high-risk infection. High diagnostic yield is demonstrated in patients with bacteraemia with or without a confirmed site of infection, particularly when combined with SPECT/CT.

Case Report of 18F-FDG PET/CT Features of Polyacrylamide Hydrogel Mammoplasty.

ABSTRACT: A 57-year-old woman with a history of previous bilateral breast polyacrylamide hydrogel injection presented for 18F-FDG PET/CT imaging to investigate recurrent retroperitoneal liposarcoma. Incidental symmetrical FDG-positive accumulation was noted in the bilateral axillae tracking between the interpectoral planes. The finding is consistent with a chronic inflammatory process secondary to the migration of the polyacrylamide hydrogel injections.

Interim Results of a Prospective Prostate-Specific Membrane Antigen-Directed Focal Stereotactic Reirradiation Trial for Locally Recurrent Prostate Cancer.

PURPOSE: To report the feasibility, toxicity, and preliminary outcomes (metabolic and biochemical) of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-directed focal prostate reirradiation using linear accelerator (LINAC)-based stereotactic body radiation treatment (SBRT). METHODS AND MATERIALS: From March 2016 to March 2019, 25 patients were enrolled in a prospective single institution trial (ACTRN12617000035325). Eligibility criteria included patients with biopsy proven isolated prostate recurrence after definitive irradiation, with concordant multiparametric MRI and 68Ga-PSMA PET/CT findings, and a prostate-specific antigen of less than 15 ng/mL at the time of recurrence. The study included a sequential dose escalation component with the first 18 patients receiving 36 Gy in 6 fractions on alternate days with subsequent patients receiving 38 Gy in 6 fractions assuming acceptable toxicity. RESULTS: Median age was 72 years (range, 62-83) with a median time between first radiation treatment and salvage SBRT of 8.3 years (range, 4.5- 13.6). Median prostate-specific antigen at reirradiation was 4.1 (range, 1.1-16.6). The median follow-up was 25 months (range, 13-46). Acute grade 1 and 2 genitourinary (GU) toxicity occurred in 6 (24%) and 1 (4%) men, respectively. Acute grade 1 gastrointestinal (GI) toxicity occurred in 8% with one acute grade 3 GI toxicity (4%) due to a rectal ulcer overlying the hydrogel. Late grade 1 and 2 GU toxicity occurred in 28% and 4%. Late grade 1 GI toxicity occurred in 8% with no grade 2 or greater toxicity. Twenty-four patients have undergone per-protocol 12-month 68Ga-PSMA PET/CT, of which 23 (92%) demonstrated a complete metabolic response. Biochemical freedom from failure was 80% at 2 years with 3 out of 4 of the biochemical failures exhibiting recurrent local disease. CONCLUSIONS: PSMA-directed salvage focal reirradiation to the prostate using linear accelerator-based SBRT is feasible and safe. Toxicity was low, with very favorable short term local and biochemical control in a carefully selected cohort of patients.

Evaluation of Fluorodeoxyglucose Positron Emission Tomography Scanning in the Neoadjuvant Therapy Paradigm in Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Little data exist on the utility of fluorodeoxyglucose positron emission tomography (FDG-PET) in operable pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant (NA) therapy. METHODS: Consecutively treated patients with potentially operable PDAC were recruited from a quaternary referral center between 2015 and 2018. Data were collated on demographic, clinical, radiological, treatment, and disease-free and overall survival (OS) outcome measures, correlated with FDG-PET findings. RESULTS: Of 115 patients recruited, 61% were deemed upfront operable (n = 70), 33% borderline (n = 38), and 6% (n = 7) locally advanced. Ninety-five (83%) received NA chemotherapy with 23 (24%) sequential radiotherapy. Sixty-nine (73%) treated with NA were resected, 37 (54%) attained an R0 resection, 43 (62%) had N1 disease with median tumor viability of 50%. The median OS in the entire cohort was 30.48 months and in those who received NA chemotherapy followed by resection 37.98 months. Twelve percent (n = 13) were upstaged during NA therapy by PET. Preoperative standardized uptake value maximum of less than 5 versus 5 or greater after NA predicted for improved OS, 42.95 months versus 26.05 months, P = 0.02. CONCLUSIONS: In this real-world cohort study of PDAC, the utility of FDG-PET in informing the patient treatment pathway was meaningfully demonstrated.

Influence of molecular classification in anaplastic glioma for determining outcome and future approach to management.

INTRODUCTION: Assess survival of patients with anaplastic glioma (AG) and the relationship to molecular subtype. METHODS: Patients with AG managed with IMRT between 2008 and 2014 were entered into a prospective database assessing relapse-free survival (RFS) and overall survival (OS). Isocitrate dehydrogenase (IDH) mutations were assessed prospectively from 2011, and subsequent testing of historical patients allowing categorisation under WHO 2016 classification as anaplastic astrocytoma IDH wild type (AAwt), anaplastic astrocytoma IDH mutated (AAmut), anaplastic oligodendroglioma (AOD) or other glial tumour (OTH). Kaplan-Meier estimates of survival distribution were calculated for the primary endpoint of overall survival and Log-rank test used to determine associated factors. RESULTS: One hundred and fifty-six patients were included with median follow-up for survivors of 4.7 years. Fifty-six per cent were managed after initial diagnosis, whilst 18% received IMRT at second or later relapse. Seventy-three per cent had temozolomide as part of initial therapy. A total of 118 or 75% of patients had IDH mutated glioma, of which 61 were AOD and 57 AAmut. There were 68 relapses and 52 deaths for a 6yrRFS of 51.2% and 6yrOS of 62.5%. AAwt was associated with worse survival (P < 0.001); and delay of RT until second or later relapse (P = 0.03). Within the 118 patients with IDH mutated tumours, 6yrOS for AOD and AAmut were 90.0% and 62.5%, respectively (P = 0.003). Also two or more craniotomies (P < 0.001), delayed RT (P = 0.006) and age <40 years (P = 0.022) were associated with worse survival on univariate analysis but only AAmut subtype and number of craniotomies on multivariate analysis. CONCLUSION: Within AG, molecular classification predicts for survival, and should influence current decision-making.

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.

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.

Dual Somatostatin Receptor/FDG PET/CT Imaging in Metastatic Neuroendocrine Tumours: Proposal for a Novel Grading Scheme with Prognostic Significance.

Background: PET scans using FDG and somatostatin receptor imaging agents have both been used to study neuroendocrine tumours. Most reports have documented the sensitivity and specificity of each radiopharmaceutical independently, and even suggested the superiority of one over the other for different grades of disease. Aim: The aim of this work was to develop a grading scheme that describes the joint results of both the FDG and somatostatin receptor imaging PET scans in staging subjects with neuroendocrine tumours in a single combined parameter. The grading scheme that has been developed is referred to as the NETPET grade. Methods: This is a retrospective study which assessed subjects who had both FDG and somatostatin receptor PET imaging at our institution within 31 days of each other. The NETPET grade was assigned by experienced nuclear medicine physicians and compared with other clinical data such as WHO grade and overall survival. Results: In the period 2011-2015 we were able to recruit 62 subjects with histologically proven metastatic neuroendocrine tumour for review. The NETPET grade incorporating both the FDG and somatostatin receptor imaging results was significantly correlated with overall survival by univariate analysis (p=0.0018), whereas in this cohort the WHO grade at the time of diagnosis did not correlate with survival. Conclusions: The NETPET grade has promise as a prognostic imaging biomarker in neuroendocrine tumours. It permits the capturing of the complexity of dual radiotracer imaging in a single parameter which describes the subjects' disease and is readily amenable to use in patient management and further research.

SPECT/CT imaging using a spiral CT scanner for anatomical localization: Impact on diagnostic accuracy and reporter confidence in clinical practice.

PURPOSE: To evaluate the incremental benefit in routine clinical practice of computed tomography (CT) scans acquired for anatomical localization on an integrated SPECT/CT which incorporates a spiral CT scanner, in comparison with conventional planar and SPECT scanning. METHODS: The first 50 studies acquired on the integrated system were evaluated by two experienced nuclear medicine physicians who were aware of the patient's clinical history. These included bone scans, gallium scans, octreotide scans, sestamibi parathyroid scans and MIBG scans. For each patient study, abnormalities were assessed on planar and SPECT images for location and provisional diagnosis and a quantitative scale was used to assess reporter confidence. The fused SPECT/CT images were then reviewed and the location and provisional diagnosis noted and reporter confidence was assessed using the same quantitative scale. RESULTS: There were 129 abnormalities detected in 50 patient studies. For localization of abnormalities, the inclusion of the CT resulted in a minor change in 16% of cases and a significant change in 11% over planar/SPECT imaging alone. The confidence of localization was improved moderately in 19% and improved significantly in 6%. For diagnosis, SPECT/CT resulted in a minor change in 10% and a significant change in 9% over planar/SPECT imaging. The confidence of diagnosis was improved moderately in 10% and improved significantly in a further 10% of cases. For the final scan interpretation, there would have been no change in 44% patients, a minor change in 30% and a significant change in 26% with the use of SPECT/CT. CONCLUSION: Use of integrated SPECT/CT with a high spatial resolution, spiral CT used for anatomical localization improves accuracy and reporter confidence in clinical practice. As a result, final reports were different in 56% of the cases, including being significantly different in 26% patients compared to reporting with planar/SPECT alone.

(68)Ga PET Ventilation and Perfusion Lung Imaging-Current Status and Future Challenges.

Gallium-68 ((68)Ga) is a positron-emitting radionuclide suitable for positron emission tomography (PET) imaging that has a number of convenient features-it has a physical half life of 68 minutes, it is generator produced at the PET facility and needs no local cyclotron, and being a radiometal is able to be chelated to a number of useful molecules for diagnostic imaging with PET. (68)Ga has recently been investigated as a radiotracer for ventilation and perfusion (V/Q) lung imaging. It is relatively easy to produce both V/Q radiopharmaceuticals labeled with (68)Ga for PET studies, it offers higher spatial resolution than equivalent SPECT studies, the short half life allows for multiple (repeated) scans on the same day, and low amounts of radiotracer can be used thus limiting the radiation dose to the subject. In the usual clinical setting requiring a V/Q scan, that of suspected pulmonary embolism, the role of (68)Ga V/Q PET may be limited from a logistical perspective, however, in nonacute applications such as lung function evaluation, radiotherapy treatment planning, and respiratory physiology investigations it would appear to be an ideal modality to employ.

68Ga-DOTATATE Breast Uptake and Expression in Breast Milk.

The excretion of Ga-DOTA-Octreotate (DOTATATE) and related somatostatin analogues in breast milk has not been demonstrated. We report a case of a 34-year-old woman, 7 months postpartum and breastfeeding, who was referred for DOTATATE imaging after the diagnosis of appendiceal carcinoid and subsequent appendectomy. Prominent breast uptake was noted. A breast milk sample from the patient at 90 minutes postinjection was assayed in a gamma counter and shown to have a concentration of 5.6 Bq/g per MBq administered. The excretion of DOTATATE in breast milk is important to consider when providing radiation safety advice to breastfeeding patients.

Artifacts and Anatomical Variants Affecting Ventilation and Perfusion Lung Imaging.

Ventilation and perfusion lung imaging continues to be an important technique in the investigation of lung disease, particularly pulmonary emboli. For the most accurate interpretation, a solid understanding of the agents available, underlying physiology, and normal variants is required. A number of ventilation agents are available ranging from true gases to aqueous aerosols and carbon nanoparticles. The addition in recent years of SPECT imaging, although improving the technique, has added to the range of artifacts and variants to be appreciated. In addition, there are uncommon conditions that can affect the scan appearance. A selection of these variants and artifacts is discussed in this article.

Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System.

OBJECTIVES: Peptide Receptor Radionuclide Therapy (PRRT) with yttrium-90 ((90)Y) and lutetium-177 ((177)Lu)-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system. METHODS: All syntheses were carried out using the Eckert & Ziegler Eurotope's Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany). Sterile, GMP-certified, no-carrier added (NCA) (177)Lu was used with GMP-certified peptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLC-SG and HPLC methods. RESULTS: A total of 17 [(177)Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [(177)Lu]-DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 ± 0.05%) and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 ± 1.5%) for this period. CONCLUSIONS: The automated synthesis of [(177)Lu]-DOTATATE using Eckert & Ziegler Eurotope's Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA (177)Lu and almost negligible radiation exposure of the operators.

Pulmonary hypertension leads to a loss of gravity dependent redistribution of regional lung perfusion: a SPECT/CT study.

OBJECTIVE: Pre-capillary pulmonary hypertension (PHT) is characterised by progressive pulmonary vascular obliteration and loss of vascular reserves. In health, regional lung perfusion redistributes under the influence of gravity due to the presence of recruitable vessels. We investigated a combined single photon emission computed tomography/CT (SPECT/CT) method for assessing the pulmonary circulation by quantifying the gravity dependent redistribution of lung perfusion. DESIGN: Characterisation of patients versus healthy controls. PATIENTS: 15 patients with pre-capillary PHT and 11 healthy controls. SETTING: University hospital clinic. INTERVENTION: Regional lung perfusion was measured using SPECT/CT in two different postures (supine vs upright). A perfusion redistribution index (PRI) was used to quantify the cranial-caudal shift in regional lung perfusion resulting from gravitational (postural) change. MAIN OUTCOME MEASURE: PRI was compared between cases and controls, and correlated with markers of disease severity in cases. RESULTS: Patients with pre-capillary PHT had notably reduced PRI compared to controls (0.02±0.06 vs. 0.28±0.15 normalised perfusion/cm, p<0.0001). PRI was significantly associated with prognostic parameters such as 6 min walk distance (r=0.60, p=0.018), functional class (p=0.008), and tricuspid annular plane systolic excursion (r=0.58, p=0.022). The receiver operating characteristic curve showed that PRI differentiated patients with pre-capillary PHT from controls with AUC=0.94 (p<0.001). CONCLUSIONS: With SPECT/CT, gravity dependent redistribution of lung perfusion can be quantified using the PRI derived from supine and upright perfusion analysis. The potential utility of PRI for the non-invasive detection of PHT and assessment of disease severity warrants further study.

Gallium-68 DOTATATE Production with Automated PET Radiopharmaceutical Synthesis System: A Three Year Experience.

OBJECTIVES: Gallium-68 (Ga-68) is an ideal research and hospital-based PET radioisotope. Currently, the main form of Ga-68 radiopharmaceutical that is being synthesised in-house is Ga-68 conjugated with DOTA based derivatives. The development of automated synthesis systems has increased the reliability, reproducibility and safety of radiopharmaceutical productions. Here we report on our three year, 500 syntheses experience with an automated system for Ga-68 DOTATATE. METHODS: The automated synthesis system we use is divided into three parts of a) servomotor modules, b) single use sterile synthesis cassettes and, c) a computerised system that runs the modules. An audit trail is produced by the system as a requirement for GMP production. The required reagents and chemicals are made in-. The Germanium breakthrough is determined on a weekly basis. Production yields for each synthesis are calculated to monitor the performance and efficiency of the synthesis. The quality of the final product is assessed after each synthesis by ITLC-SG and HPLC methods. RESULTS: A total of 500 Ga-68 DOTATATE syntheses (>800 patient doses) were performed between March 2011 and February 2014. The average generator yield was 81.3±0.2% for 2011, 76.7±0.4% for 2012 and 75.0±0.3% for 2013. Ga-68 DOTATATE yields for 2011, 2012, and 2013 were 81.8±0.4%, 82.2±0.4% and 87.9±0.4%, respectively. These exceed the manufacturer's expected value of approximately 70%. Germanium breakthrough averaged 8.6×10(-6)% of total activity which is well below the recommended level of 0.001%. The average ITLC-measured radiochemical purity was above 98.5% and the average HPLC-measured radiochemical purity was above 99.5%. Although there were some system failures during synthesis, there were only eight occasions where the patient scans needed to be rescheduled. CONCLUSION: In our experience the automated synthesis system performs reliably with a relatively low incident of failures. Our system had a consistent and reliable Ga-68 DOTATATE output with high labelling efficiency and purity. There is minimal operator intervention and radiation exposure. The system is GMP-compliant and has low maintenance and acceptable running costs. This system together with the recommended (68)Ge/(68)Ga generator is well suited for use in a hospital-based radiopharmacy.