Bone SPECT/CT in the Evaluation of Painful Total Ankle Replacement: Validation of Localization Scheme and Preliminary Evaluation of Diagnostic Patterns.

PURPOSE: Third-generation total ankle replacement (TAR) is an increasingly popular and effective treatment for end-stage osteoarthritis, yet identifying causes of failure remains challenging. We evaluated integrated bone SPECT/CT in recurrent pain after TAR by validating a standardized reporting scheme, identifying uptake patterns, and assessing diagnostic performance and impact on clinical management. PATIENTS AND METHODS: A total of 24 TARs in 16 patients with persistent or recurrent pain received integrated bone SPECT/CT using diagnostic CT settings. Images were retrospectively reviewed, and a novel localization scheme was validated by assessing interrater agreement. Distinct uptake patterns were identified, and diagnostic test characteristics were estimated. Reference standard consisted of clinical follow-up, laboratory findings, and subsequent procedures, including revision surgery. RESULTS: Standardized scoring of bone SPECT/CT uptake was highly reproducible (intraclass correlation coefficient, 0.79; 95% confidence interval [CI], 0.75-0.82). The final diagnoses were gutter impingement (n = 12), periprosthetic (stress) fracture (n = 5), loosening (n = 5), tarsal arthritis (n = 1), and erysipelas (n = 1). Overall, the diagnostic test characteristics of bone SPECT/CT were as follows: sensitivity of 100% (95% CI, 82%-100%), specificity of 80% (95% CI, 28%-99%), and accuracy of 96% (95% CI, 79%-100%). Gutter impingement, periprosthetic fracture, and loosening were correctly identified in all cases revealing distinct uptake patterns. Importantly, persistent diffuse uptake was frequently observed, warranting cautious interpretation. Bone SPECT/CT impacted clinical management in 86%, with symptomatic improvement in 83% of patients. CONCLUSIONS: Integrated bone SPECT/CT of painful TARs may benefit from standardized localization to reveal distinct uptake patterns representing common complications after TAR. Initial results show highly promising diagnostic value with potentially important impact on clinical management.

Standardized added metabolic activity (SAM) IN ¹8F-FDG PET assessment of treatment response in colorectal liver metastases.

PURPOSE: Standardized added metabolic activity (SAM) is a PET parameter for assessing the total metabolic load of malignant processes, avoiding partial volume effects and lesion segmentation. The potential role of this parameter in the assessment of response to chemotherapy and bevacizumab was tested in patients with metastatic colorectal cancer with potentially resectable liver metastases (mCRC). METHODS: (18)F-FDG PET/CT was performed in 18 mCRC patients with liver metastases before treatment and after five cycles of FOLFOX/FOLFIRI and bevacizumab. Of the 18 patients, 16 subsequently underwent resection of liver metastases. Baseline and follow-up SUVmax, and SAM as well as reduction in SUVmax (∆SUVmax) and SAM (∆SAM) of all liver metastases were correlated with morphological response, and progression-free and overall survival (PFS and OS). RESULTS: A significant reduction in metabolic activity of the liver metastases was seen after chemotherapy with a median ∆SUVmax of 25.3% and ∆SAM of 94.5% (p = 0.033 and 0.003). Median baseline SUVmax and SAM values were significantly different between morphological responders and nonresponders (3.8 vs. 7.2, p = 0.021; and 34 vs. 211, p = 0.002, respectively), but neither baseline PET parameters nor morphological response was correlated with PFS or OS. Follow-up SUVmax and SAM as well as ∆SAM were found to be prognostic factors. The median PFS and OS in the patient group with a high follow-up SUVmax were 10.4 months and 32 months, compared to a median PFS of 14.7 months and a median OS which had not been reached in the group with a low follow-up SUVmax (p = 0.01 and 0.003, respectively). The patient group with a high follow-up SAM and a low ∆SAM had a median PFS and OS of 9.4 months and 32 months, whereas the other group had a median PFS of 14.7 months and a median OS which had not been reached (p = 0.002 for both PFS and OS). CONCLUSION: (18)F-FDG PET imaging is a useful tool to assess treatment response and predict clinical outcome in patients with mCRC who undergo chemotherapy before liver metastasectomy. Follow-up SUVmax, follow-up SAM and ∆SAM were found to be significant prognostic factors for PFS and OS.

Standardized added metabolic activity (SAM): a partial volume independent marker of total lesion glycolysis in liver metastases.

PURPOSE: The standardized added metabolic activity (SAM) is a new marker of total lesion glycolysis that avoids partial volume effect (PVE) and thresholding. SAM is calculated by drawing a volume of interest (VOI(1)) around the tumour and a larger VOI (VOI(2)) around VOI(1). Subtracting the background activity in VOI(2)-VOI(1) from VOI(1) yields SAM. If VOI(1) is set at a reasonable distance from the tumour, PVE are avoided. Phantom and initial clinical validation data are presented. METHODS: Spheres of a Jaszczak phantom were filled with a 5.4, 3.64 and 2.0 times higher concentration relative to background activity and positron emission tomography (PET) data were acquired during 10 min. SAM of all spheres was expressed as a percentage of the expected value (the actual activity ratio minus 1). In 15 patients a 10-min list-mode acquisition PET study centred on their primary squamous cell carcinoma (PSCC) was performed and images of 1-10 min reconstructed. SAM1-9min values of PSCC were expressed as a percentage of SAM10min. Nineteen patients suffering from liver metastases treated with chemotherapy underwent PET/CT prior to (scan 1) and after 3-6 cycles of chemotherapy (scan 2). SAM and maximum standardized uptake values (SUV(max)) of the liver lesions on scan 1 (SAM1 and SUV(max)1) and the percentage reduction between both ΔSAM and ΔSUV(max) were related to Response Evaluation Criteria in Solid Tumors (RECIST) response. RESULTS: For the phantom acquisitions, the mean normalized SAM/sphere volume calculated was 94.9 % (SD 5.9 %) of the expected value. In the PSCC patients, the mean difference between SAM1min and SAM10min was only 4 % (SD 5 %). SUV(max)1min and SUV(max)10min proved to be not significantly different, but the variability was slightly larger than that of SAM (SD 6.4 %). SAM1 and ΔSAM values for responders versus non-responders were, respectively, 57 (SD 119) versus 297 (SD 625) for SAM1 (p = 0.2) and 99 % (SD 3 %) versus 32 % (SD 44 %) for ΔSAM (p = 0.001). SUV(max)1 and ΔSUV(max) values in responders versus non-responders were, respectively, 3.9 (SD 2.4) versus 6.3 (SD 3.1) for SUV(max)1 (p = 0.08) and 94 % (SD 17) versus 7 % (SD 40 %) for ΔSUV(max) (p = 0.0001). The AUC of ΔSAM and ΔSUV(max) were not significantly different on receiver-operating characteristic (ROC) analysis (AUC 1.0 and 0.99, respectively, p = 0.6). CONCLUSION: SAM is a promising parameter for tumour response assessment of liver metastases by means of (18)F-fluorodeoxyglucose PET.

Tumor perfusion using first-pass F-18 FDG PET images.

Many reports in the literature have focused on FDG PET imaging at conventional (60 minutes after injection) or delayed (several hours after injection) intervals, which exploits increased glycolysis in tumors for diagnosis. However, in rapidly growing tumors, accelerated glycolysis is, among other factors, mediated by hypoxia and poor perfusion. Interestingly, first-pass (0-2 minutes after injection) FDG PET images were shown to provide an index of perfusion. Here, we illustrate that tracer uptake by various (parts of) tumors is discrepant between first-pass and conventional PET images, probably reflecting the direct control of glucose transporter overexpression by hypoxia, resulting from poor perfusion (Warburg's hypothesis).

Intra-arterial treatment with 9°Y microspheres for hepatocellular carcinoma: 4 years experience at the Ghent University Hospital.

PURPOSE: We report on our experience in terms of eligibility, safety, response and survival for treatment of hepatocellular carcinoma (HCC) with (90)Y microspheres. Secondly, we investigated the urinary excretion of (90)Y following treatment. METHODS: We retrospectively reviewed all HCC patients referred to our department for (90)Y microsphere treatment. We recorded reasons for not proceeding to actual treatment. In case treatment was performed, we assessed the tolerance (Common Terminology Criteria for Adverse Events v3.0, CTCAE v3.0), the response [modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria] and long-term survival (Kaplan-Meier). The urinary excretion was estimated by 12-h urine collections post-injection for analysis in a gamma counter. RESULTS: Forty-three HCC patients were referred for radioembolization. Fourteen patients were excluded, mainly due to unfavourable (99m)Tc-macroaggregated albumin (MAA) distribution. Twenty-nine patients were treated with (90)Y microspheres (TheraSphere, mean activity 2.17 GBq). In four patients severe clinical adverse events were encountered, however only in one case clearly related to the therapy. Twenty patients were assessable by mRECIST: complete response in 15%, partial response in 35%, stable disease in 30% and progression in 20% were observed. A median survival of 12.3 months (95% confidence interval 9.4-15.2) was estimated. Concerning the substudy on urinary excretion, only 0.0025% of the administered activity was excreted in the urine within the first 12 h following TheraSphere. CONCLUSION: Following a strict workup before admitting patients to radioembolization with TheraSphere, we found good clinical tolerance in the vast majority of patients. Radiological response assessment yielded an overall response rate of 50%, when evaluated early following treatment. Urine analysis showed consistently only low activities of (90)Y excreted in the urine.

99mTc-labelled macroaggregated albumin (MAA) scintigraphy for planning treatment with 90Y microspheres.

PURPOSE: 90Y microspheres are used for intra-arterial treatment of liver tumours. In the patient preparation, a hepatic angiogram is performed and all arteries that could transport microspheres from the targeted liver vasculature to extrahepatic organs are blocked. 99mTc-labelled macroaggregated albumin (MAA) is injected intra-arterially to simulate the treatment and whole-body scintigraphy and single photon emission computed tomography (SPECT) of the abdomen are performed. METHODS: Various aspects of lung shunt fraction (LSF) estimation were studied: interobserver and intrapatient variability, influence of scan quality and underlying disease. Secondly, the interobserver variability in reading the MAA SPECT of the abdomen was investigated. We reviewed 90 whole-body scans and 20 SPECT scans performed at our institution. Readers were blinded to each other's findings. Scoring the scan quality was based on the visualization of tracer degradation. RESULTS: The mean difference in LSF between the readers was 1%. In 1 of 23 patients who underwent repeated MAA injections a marked change in LSF was observed. No significant differences in LSF were recorded for primary versus secondary liver tumours. There was a correlation between scan quality and LSF, suggesting that low scan quality leads to overestimation of the LSF. Concordant results in ruling out the presence of extrahepatic tracer deposition were reached in 17 of 20 scans (85%). CONCLUSION: Interobserver and intrapatient variability in LSF calculation was limited. LSF was clearly dependent on scan quality. The underlying disease had no significant impact on the LSF. Interobserver variability for reading the MAA SPECT scans was acceptable.