Initial experience in staging primary oesophageal/gastro-oesophageal cancer with 18F-FDG PET/MRI.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) may improve cancer staging by combining sensitive cancer detection with high-contrast resolution and detail. We compared the diagnostic performance of 18F-FDG PET/MRI to 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging oesophageal/gastro-oesophageal cancer. Following ethical approval and informed consent, participants with newly diagnosed primary oesophageal/gastro-oesophageal cancer were enrolled. Exclusions included prior/concurrent malignancy. Following 324 ± 28 MBq 18F-FDG administration and 60-min uptake, PET/CT was performed, immediately followed by integrated PET/MRI from skull base to mid-thigh. PET/CT was interpreted by two dual-accredited nuclear medicine physicians and PET/MRI by a dual-accredited nuclear medicine physician/radiologist and cancer radiologist in consensus. Per-participant staging was compared with the tumour board consensus staging using the McNemar test, with statistical significance at 5%. RESULTS: Out of 26 participants, 22 (20 males; mean ± SD age 68.8 ± 8.7 years) completed 18F-FDG PET/CT and PET/MRI. Compared to the tumour board, the primary tumour was staged concordantly in 55% (12/22) with PET/MRI and 36% (8/22) with PET/CT; the nodal stage was concordant in 45% (10/22) with PET/MRI and 50% (11/22) with PET/CT. There was no statistical difference in PET/CT and PET/MRI staging performance (p > 0.05, for T and N staging). The staging of distant metastases was concordant with the tumour board in 95% (21/22) with both PET/MRI and PET/CT. Of participants with distant metastatic disease, PET/MRI detected additional metastases in 30% (3/10). CONCLUSION: In this preliminary study, compared to 18F-FDG PET/CT, 18F-FDG PET/MRI showed non-significant higher concordance with T-staging, but no difference with N or M-staging. Additional metastases detected by 18F-FDG PET/MRI may be of additive clinical value.

Role of intravoxel incoherent motion parameters in gastroesophageal cancer: relationship with 18F-FDG-positron emission tomography, computed tomography perfusion and magnetic resonance perfusion imaging parameters.

BACKGROUND: Identification of pretherapeutic predictive markers in gastro-esophageal cancer is essential for individual-oriented treatment. This study evaluated the relationship of multimodality parameters derived from intravoxel incoherent motion method (IVIM), 18F-FDG-positron emission tomography (PET), computed tomography (CT) perfusion and dynamic contrast enhanced magnetic resonance imaging (MRI) in patients with gastro-esophageal cancer and investigated their histopathological correlation. METHODS: Thirty-one consecutive patients (28 males; median age 63.9 years; range 37-84 years) with gastro-esophageal adenocarcinoma (N.=22) and esophageal squamous cell carcinoma (N.=9) were analyzed. IVIM parameters: pseudodiffusion (D*), perfusion fraction (fp), true diffusion (D) and the threshold b-value (bval); PET-parameters: SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG); CT perfusion parameters: blood flow (BF), blood volume (BV) and mean transit time (MTT); and MR perfusion parameters: time to enhance, positive enhancement integral, time-to-peak (TTP), maximum-slope-of-increase, and maximum-slope-of-decrease were determined, and correlated to each other and to histopathology. RESULTS: IVIM and PET parameters showed significant negative correlations: MTV and bval (rs =-0.643, P=0.002), TLG and bval (rs=-0.699, P<0.01) and TLG and fp (rs=-0.577, P=0.006). Positive correlation was found for TLG and D (rs=0.705, P=0.000). Negative correlation was found for bval and staging (rs=0.590, P=0.005). Positive correlation was found for positive enhancement interval and BV (rs=0.547, P=0.007), BF and regression index (rs=0.753, P=0.005) and for time-to-peak and staging (rs=0.557, P=0.005). CONCLUSIONS: IVIM parameters (bval, fp, D) provide quantitative information and correlate with PET parameters (MTV, TLG) and staging. IVIM might be a useful tool for additional characterization of gastro-esophageal cancer.

Radiation dosimetry of [18F]-PSS232-a PET radioligand for imaging mGlu5 receptors in humans.

PURPOSE: (E)-3-(pyridin-2-ylethynyl)cyclohex-2-enone O-(3-(2-[18F]-fluoroethoxy)propyl) oxime ([18F]-PSS232) is a new PET tracer for imaging of metabotropic glutamate receptor subtype 5 (mGlu5), and has shown promising results in rodents and humans. The aim of this study was to estimate the radiation dosimetry and biodistribution in humans, to assess dose-limiting organs, and to demonstrate safety and tolerability of [18F]-PSS232 in healthy volunteers. METHODS: PET/CT scans of six healthy male volunteers (mean age 23.5 ± 1.7; 21-26 years) were obtained after intravenous administration of 243 ± 3 MBq of [18F]-PSS232. Serial whole-body (vertex to mid-thigh) PET scans were assessed at ten time points, up to 90 min after tracer injection. Calculation of tracer kinetics and cumulated organ activities were performed using PMOD 3.7 software. Dosimetry estimates were calculated using the OLINDA/EXM software. RESULTS: Injection of [18F]-PSS232 was safe and well tolerated. Organs with highest absorbed doses were the gallbladder wall (0.2295 mGy/MBq), liver (0.0547 mGy/MBq), and the small intestine (0.0643 mGy/MBq). Mean effective dose was 3.72 ± 0.12 mSv/volunteer (range 3.61-3.96 mSv; 0.0153 mSv/MBq). CONCLUSION: [18F]-PSS232, a novel [18F]-labeled mGlu5 tracer, showed favorable dosimetry values. Additionally, the tracer was safe and well tolerated.

Exploratory radiomic features from integrated 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging are associated with contemporaneous metastases in oesophageal/gastroesophageal cancer.

PURPOSE: The purpose of this study was to determine if 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) features are associated with contemporaneous metastases in patients with oesophageal/gastroesophageal cancer. METHODS: Following IRB approval and informed consent, patients underwent a staging PET/MRI following 18F-FDG injection (326 ± 28 MBq) and 156 ± 23 min uptake time. First-order histogram and second-order grey level co-occurrence matrix features were computed for PET standardized uptake value (SUV) and MRI T1-W, T2-W, diffusion weighted (DWI) and apparent diffusion coefficient (ADC) images for the whole tumour volume. K-means clustering assessed the correlation of feature-pairs with metastases. Multivariate analysis of variance (MANOVA) was performed to assess the statistical separability of the groups identified by feature-pairs. Sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy (ACC) were calculated for these features and compared with SUVmax, ADCmean and maximum diameter alone for predicting contemporaneous metastases. RESULTS: Twenty patients (18 males, 2 female; median 67 years, range 52-86) comprised the final study cohort; ten patients had metastases. Lower second-order SUV entropy combined with higher second-order ADC entropy were the best feature-pair for discriminating metastatic patients, MANOVA p value <0.001 (SN = 80%, SP = 80%, PPV = 80%, NPV = 80%, ACC = 80%). SUVmax (SN = 30%, SP = 80%, PPV = 60%, NPV = 53%, ACC = 55%), ADCmean (SN = 20%, SP = 70%, PPV = 40%, NPV = 47%, ACC = 45%) and tumour maximum diameter (SN = 10%, SP = 90%, PPV = 50%, NPV = 50%, ACC = 50%) had poorer sensitivity and accuracy. CONCLUSION: High ADC entropy combined with low SUV entropy is associated with a higher prevalence of metastases and a promising initial signature for future study.

Comparing diagnostic accuracy of 18F-FDG-PET/CT, contrast enhanced CT and combined imaging in patients with suspected vascular graft infections.

BACKGROUND: To evaluate the diagnostic accuracy of positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (PET/CT), contrast-enhanced CT (CE-CT), and a combined imaging approach (CE-PET/CT) in patients with suspected vascular graft infection (VGI). METHODS: PET/CT and CE-CT were performed prospectively in 23 patients with suspected VGI. Diagnostic accuracy for PET/CT was assessed by using previously suggested cut-off points for maximum standardized uptake values (SUVmax) measured in the vicinity of the graft. Using a new 4-point scale for visual grading, two readers independently assessed the diagnostic accuracy for CE-CT and combined CE-PET/CT. Microbiological culture, obtained after open biopsy or graft explantation, and clinical follow-up of the patients served as the standard of reference. RESULTS: Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of PET/CT for the diagnosis of VGI was 100%, 50%, 100%, 72.2%, and 78.3%, using the most favorable SUVmax cut-off ≥ 4.9. Respective values for CE-CT were 100%, 50%, 100%, 72.2%, and 78.3% for reader 1, and 92.3%, 80%, 88.9%, 85.7%, and 86.9% for reader 2; while respective values for combined CE-PET/CT were 100%, 70%, 100%, 81.3%, and 86.9% for reader 1, and 100%, 80%, 100%, 86.7%, and 91.3% for reader 2. Additionally, imaging provided a conclusive clinical diagnosis in patients without graft infection (i.e., other sites of infection): five of ten patients with CE-CT, six of ten patients with PET/CT, and seven of ten patients with combined CE-PET/CT. CONCLUSION: The diagnostic accuracy of combined CE-PET/CT in patients with suspected VGI is very high. The combination of the high sensitivity of PET/CT in detecting metabolically active foci in infection, and the high specificity of CE-CT in detecting anatomic alterations, appears to be the reason why combined imaging outperforms stand-alone imaging in diagnosing VGI and may be supportive in future decision-making of difficult cases of suspected VGI. Clinical Trials.gov Identifier: NCT01821664.

Radiomics in esophageal and gastric cancer.

Esophageal, esophago-gastric, and gastric cancers are major causes of cancer morbidity and cancer death. For patients with potentially resectable disease, multi-modality treatment is recommended as it provides the best chance of survival. However, quality of life may be adversely affected by therapy, and with a wide variation in outcome despite multi-modality therapy, there is a clear need to improve patient stratification. Radiomic approaches provide an opportunity to improve tumor phenotyping. In this review we assess the evidence to date and discuss how these approaches could improve outcome in esophageal, esophago-gastric, and gastric cancer.

Feasibility of 18F-FDG Dose Reductions in Breast Cancer PET/MRI.

The goal of this study was to determine the level of clinically acceptable 18F-FDG dose reduction in time-of-flight PET/MRI in patients with breast cancer. Methods: Twenty-six consecutive women with histologically proven breast cancer were analyzed (median age, 51 y; range, 34-83 y). Simulated dose-reduced PET images were generated by unlisting the list-mode data on PET/MRI. The acquired 20-min PET frame was reconstructed in 5 ways: a reconstruction of the first 2 min with 3 iterations and 28 subsets for reference, and reconstructions simulating 100%, 20%, 10%, and 5% of the original dose. General image quality and artifacts, image sharpness, image noise, and lesion detectability were analyzed using a 4-point scale. Qualitative parameters were compared using the nonparametric Friedman test for multiple samples and the Wilcoxon signed-rank test for paired samples. Different groups of independent samples were compared using the Mann-Whitney U test. Results: Overall, 355 lesions (71 lesions with 5 different reconstructions each) were evaluated. The 20-min reconstruction with 100% injected dose showed the best results in all categories. For general image quality and artifacts, image sharpness, and noise, the reconstructions with a simulated dose of 20% and 10% were significantly better than the 2-min reconstructions (P ≤ 0.001). Furthermore, 20%, 10%, and 5% reconstructions did not yield results different from those of the 2-min reconstruction for detectability of the primary lesion. For 10% of the injected dose, a calculated mean dose of 22.6 ± 5.5 MBq (range, 17.9-36.9 MBq) would have been applied, resulting in an estimated whole-body radiation burden of 0.5 ± 0.1 mSv (range, 0.4-0.7 mSv). Conclusion: Ten percent of the standard dose of 18F-FDG (reduction of ≤90%) results in clinically acceptable PET image quality in time-of-flight PET/MRI. The calculated radiation exposure would be comparable to the effective dose of a single digital mammogram. A reduction of radiation burden to this level might justify partial-body examinations with PET/MRI for dedicated indications.

WITHDRAWN: Evaluation of multifunctional imaging parameters in gastro-oesophageal cancer using F-18-FDG-PET/CT with integrated perfusion CT.

Ahead of Print article withdrawn by publisher.

[18F]Fluorocholine Uptake of Parathyroid Adenoma Is Correlated with Parathyroid Hormone Level.

PURPOSE: The aim of the study was to investigate the relationship between [18F]fluoromethyl-dimethyl-2-hydroxyethylammonium ([18F]FCh) positron emission tomography (PET) parameters, laboratory parameters, and postoperative histopathological results in patients with primary hyperparathyroidism (pHPT) due to parathyroid adenomas. PROCEDURES: This retrospective study was conducted in 52 patients with biochemically proven pHPT. [18F]FCh-PET parameters (maximum standardized uptake value: SUVmax) in early phase (after 2 min) and late phase (after 50 min), metabolic volume, and adenoma-to-background ratio (ABR), preoperative laboratory results (PTH and serum calcium concentration), and postoperative histopathology (location, size, volume, and weight of adenoma) were assessed. Relationship of PET parameters, laboratory parameters, and histopathological parameters was assessed using the Mann-Whitney U test and Spearman correlation coefficient. MRI characteristics of parathyroid adenomas were also analyzed. RESULTS: The majority of patients underwent a PET/MR scan, 42 patients (80.7 %); 10 patients (19.3 %) underwent PET/CT. We found a strong positive correlation between late-phase SUVmax and preoperative PTH level (r = 0.768, p < 0.001) and between late-phase ABR and preoperative PTH level (r = 0.680, p < 0.001). The surgical specimen volume was positively correlated with the PET/MR lesion volume (r = 0.659, p < 0.001). No significant association was observed between other [18F]FCh-PET parameters, laboratory parameters, and histopathological findings. Cystic adenomas were larger than non-cystic adenomas (p = 0.048). CONCLUSIONS: [18F]FCh uptake of parathyroid adenomas is strongly correlated with preoperative PTH serum concentration. Therefore, the preoperative PTH level might potentially be able to predict success of [18F]FCh-PET imaging in hyperparathyroidism, with higher lesion-to-background ratios being expected in patients with high PTH. PET/MR is accurate in estimating the volume of parathyroid adenomas.

PET/MR Outperforms PET/CT in Suspected Occult Tumors.

BACKGROUND: To compare the diagnostic accuracy of PET/MR and PET/CT in patients with suspected occult primary tumors. METHODS: This prospective study was approved by the institutional review board. Sequential PET/CT-MR was performed in 43 patients (22 male subjects; median age, 58 years; range, 20-86 years) referred for suspected occult primary tumors. Patients were assessed with PET/CT and PET/MR for the presence of a primary tumor, lymph node metastases, and distant metastases. Wilcoxon signed-rank test was performed to compare the diagnostic accuracy of PET/CT and PET/MR. RESULT: According to the standard of reference, a primary lesion was found in 14 patients. In 16 patients, the primary lesion remained occult. In the remaining 13 patients, lesions proved to be benign. PET/MR was superior to PET/CT for primary tumor detection (sensitivity/specificity, 0.85/0.97 vs 0.69/0.73; P = 0.020) and comparable to PET/CT for the detection of lymph node metastases (sensitivity/specificity, 0.93/1.00 vs 0.93/0.93; P = 0.157) and distant metastases (sensitivity/specificity, 1.00/0.97 vs 0.82/1.00; P = 0.564). PET/CT tended to misclassify physiologic FDG uptake as malignancy compared with PET/MR (8 patients vs 1 patient). CONCLUSIONS: PET/MR outperforms PET/CT in the workup of suspected occult malignancies. PET/MR may replace PET/CT to improve clinical workflow.

Clinical evaluation of a block sequential regularized expectation maximization reconstruction algorithm in 18F-FDG PET/CT studies.

PURPOSE: To investigate the clinical performance of a block sequential regularized expectation maximization (BSREM) penalized likelihood reconstruction algorithm in oncologic PET/computed tomography (CT) studies. METHODS: A total of 410 reconstructions of 41 fluorine-18 fluorodeoxyglucose-PET/CT studies of 41 patients with a total of 2010 lesions were analyzed by two experienced nuclear medicine physicians. Images were reconstructed with BSREM (with four different ß values) or ordered subset expectation maximization (OSEM) algorithm with/without time-of-flight (TOF/non-TOF) corrections. OSEM reconstruction postfiltering was 4.0 mm full-width at half-maximum; BSREM did not use postfiltering. Evaluation of general image quality was performed with a five-point scale using maximum intensity projections. Artifacts (category 1), image sharpness (category 2), noise (category 3), and lesion detectability (category 4) were analyzed using a four-point scale. Size and maximum standardized uptake value (SUVmax) of lesions were measured by a third reader not involved in the image evaluation. RESULTS: BSREM-TOF reconstructions showed the best results in all categories, independent of different body compartments. In all categories, BSREM non-TOF reconstructions were significantly better than OSEM non-TOF reconstructions (P<0.001). In almost all categories, BSREM non-TOF reconstruction was comparable to or better than the OSEM-TOF algorithm (P<0.001 for general image quality, image sharpness, noise, and P=1.0 for artifact). Only in lesion detectability was OSEM-TOF significantly better than BSREM non-TOF (P<0.001). Both BSREM-TOF and BSREM non-TOF showed a decreasing SUVmax with increasing ß values (P<0.001) and TOF reconstructions showed a significantly higher SUVmax than non-TOF reconstructions (P<0.001). CONCLUSION: The BSREM reconstruction algorithm showed a relevant improvement compared with OSEM reconstruction in PET/CT studies in all evaluated categories. BSREM might be used in clinical routine in conjunction with TOF to achieve better/higher image quality and lesion detectability or in PET/CT-systems without TOF-capability for enhancement of overall image quality as well.

Visualization of Parathyroid Hyperplasia Using 18F-Fluorocholine PET/MR in a Patient With Secondary Hyperparathyroidism.

Several imaging modalities exist for the detection of parathyroid adenomas in patients with primary hyperparathyroidism. Unlike solitary parathyroid adenoma, parathyroid hyperplasia in patients with secondary hyperparathyroidism hitherto is difficult to assess with any imaging modality. Our case of a young patient with chronic kidney failure illustrates that F-fluorocholine PET/MR might be an imaging tool suitable for the diagnosis and presurgical assessment of parathyroid hyperplasia.

Determinants of diagnostic performance of 18F-FDG PET/CT in patients with fever of unknown origin.

OBJECTIVES: There is uncertainty about patient selection and the adequate timing at which fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) is indicated in the diagnostic work-up of fever of unknown origin (FUO). The aim of this study was to determine the diagnostic performance of F-FDG PET/CT in patients with FUO. METHODS: All consecutive patients who underwent F-FDG PET/CT at the University Hospital Zurich because of FUO between 2006 and 2012 were included in this retrospective, observational study. RESULTS: A total of 76 patients [70% men, median (interquartile range) age 60 (47-67) years] were included. F-FDG PET/CT showed characteristically increased F-FDG activity in 56 patients (74%), leading to confirmation of or change in the suspected cause of FUO in 57 and 17%, respectively. The final diagnosis after F-FDG PET/CT included infection (21%), malignancy (22%), noninfectious inflammatory disease (12%), others (5%), or an unknown cause (40%). The success rate, sensitivity, and specificity of F-FDG PET/CT were 60, 77, and 31%, respectively. Sensitivity was highest in patients with suspected malignancy (100%, 95% confidence interval 79-100%). Diagnostic performance was independent of the investigated variables other than suspected infection as a cause of FUO (odds ratio 0.1, 95% confidence interval 0.01-0.8, P=0.033). CONCLUSION: The diagnostic performance of F-FDG PET/CT was significantly higher in patients with suspected malignancy causing a FUO compared with suspected infection or noninfectious inflammatory disease. However, it was independent of the baseline characteristics and duration of fever. This supports the recommendation to perform F-FDG PET/CT early in the diagnostic work-up of FUO, which may shorten disease duration and lower health costs, particularly when infection or malignancy is suspected.

Intra-individual comparison of PET/CT with different body weight-adapted FDG dosage regimens.

BACKGROUND: 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/ computed tomography (CT) imaging demands guidelines to safeguard sufficient image quality at low radiation exposure. Various FDG dose regimes have been investigated; however, body weight-adapted dose regimens and related image quality (IQ) have not yet been compared in the same patient. PURPOSE: To investigate the relationship between FDG dosage and image quality in PET/CT in the same patient and determine prerequisites for low dosage scanning. MATERIAL AND METHODS: This study included 61 patients undergoing a clinically indicated PET/CT imaging study and follow-up with a normal (NDS, 5 MBq/kg body weight [BW]) and low dosage scanning protocol (LDS, 4 MBq/kg BW), respectively, using a Discovery VCT64 scanner. Two blinded and independent readers randomly assessed IQ of PET using a 5-point Likert scale and signal-to-noise ratio (SNR) of the liver. RESULTS: Body mass index (BMI) was significantly lower at LDS (P = 0.021) and represented a significant predictor of SNR at both NDS (P < 0.001) and LDS (P = 0.005). NDS with a mean administered activity of 340 MBq resulted in significantly higher IQ (P < 0.001) and SNR as compared with LDS with a mean of 264 MBq (F-value = 23.5, P < 0.001, mixed model ANOVA adjusted for covariate BMI). Non-diagnostic IQ at LDS was associated with a BMI > 22 kg/m(2). CONCLUSION: FDG dosage significantly predicts IQ and SNR in PET/CT imaging as demonstrated in the same patient with optimal IQ achieved at 5 MBq/kg BM. PET/CT imaging at 4 MBq/kg BW may only be recommended in patients with a BMI ≤ 22 kg/m(2) to maintain diagnostic IQ.

Dosimetry and first clinical evaluation of the new 18F-radiolabeled bombesin analogue BAY 864367 in patients with prostate cancer.

UNLABELLED: The aim of this first-in-man study was to demonstrate the feasibility, safety, and tolerability, as well as provide dosimetric data and evaluate the imaging properties, of the bombesin analogue BAY 864367 for PET/CT in a small group of patients with primary and recurrent prostate cancer (PCa). METHODS: Ten patients with biopsy-proven PCa (5 with primary PCa and 5 with prostate-specific antigen recurrence after radical prostatectomy) were prospectively selected for this exploratory clinical trial with BAY 864367, a new (18)F-labeled bombesin analogue. PET scans were assessed at 6 time points, up to 110 min after intravenous administration of 302 ± 11 MBq of BAY 864367. Imaging results were compared with (18)F-fluorocholine PET/CT scans. Dosimetry was calculated using the OLINDA/EXM software. RESULTS: Three of 5 patients with primary disease showed positive tumor delineation in the prostate, and 2 of 5 patients with biochemical relapse showed a lesion suggestive of recurrence on the BAY 864367 scan. Tumor-to-background ratio averaged 12.9 ± 7.0. The ratio of malignant prostate tissue to normal prostate tissue was 4.4 ± 0.6 in 3 patients with tracer uptake in the primary PCa. Mean effective dose was 4.3 ± 0.3 mSv/patient (range, 3.7-4.9 mSv). CONCLUSION: BAY 864367, a novel (18)F-labeled bombesin tracer, was successfully investigated in a first-in-man clinical trial of PCa and showed favorable dosimetric values. Additionally, the application was safe and well tolerated. The tracer delineated tumors in a subset of patients, demonstrating the potential of gastrin-releasing-peptide receptor imaging.

Perfusion CT best predicts outcome after radioembolization of liver metastases: a comparison of radionuclide and CT imaging techniques.

OBJECTIVE: To determine the best predictor for the response to and survival with transarterial radioembolisation (RE) with (90)yttrium microspheres in patients with liver metastases. METHODS: Forty consecutive patients with liver metastases undergoing RE were evaluated with multiphase CT, perfusion CT and (99m)Tc-MAA SPECT. Arterial perfusion (AP) from perfusion CT, HU values from the arterial (aHU) and portal venous phase (pvHU) CT, and (99m)Tc-MAA uptake ratio of metastases were determined. Morphologic response was evaluated after 4 months and available in 30 patients. One-year survival was calculated with Kaplan-Meier curves. RESULTS: We found significant differences between responders and non-responders for AP (P < 0.001) and aHU (P = 0.001) of metastases, while no differences were found for pvHU (P = 0.07) and the (99m)Tc-MAA uptake ratio (P = 0.40). AP had a significantly higher specificity than aHU (P = 0.003) for determining responders to RE. Patients with an AP >20 ml/100 ml/min had a significantly (P = 0.01) higher 1-year survival, whereas an aHU value >55 HU did not discriminate survival (P = 0.12). The Cox proportional hazard model revealed AP as the only significant (P = 0.02) independent predictor of survival. CONCLUSION: Compared to arterial and portal venous enhancement and the (99m)Tc-MAA uptake ratio of liver metastases, the AP from perfusion CT is the best predictor of morphologic response to and 1-year survival with RE. KEY POINTS: • Perfusion CT allows for calculation of the liver arterial perfusion. • Arterial perfusion of liver metastases differs between responders and non-responders to RE. • Arterial perfusion can be used to select patients responding to RE.

Early treatment response evaluation after yttrium-90 radioembolization of liver malignancy with CT perfusion.

PURPOSE: To evaluate computed tomography (CT) perfusion for assessment of early treatment response after transarterial radioembolization of patients with liver malignancy. MATERIALS AND METHODS: Dynamic contrast-enhanced CT liver perfusion was performed before and 4 weeks after transarterial radioembolization in 40 patients (25 men and 15 women; mean age, 64 y ± 11; range, 35-80 y) with liver metastases (n = 27) or hepatocellular carcinoma (HCC) (n = 13). Arterial perfusion (AP) of tumors derived from CT perfusion and tumor diameters were measured on CT perfusion before and after transarterial radioembolization. Success of transarterial radioembolization was evaluated on morphologic follow-up imaging (median follow-up time, 4 mo) based on Response Evaluation Criteria in Solid Tumors (Version 1.1). CT perfusion parameters before and after transarterial radioembolization for different response groups were compared. Kaplan-Meier curves were plotted to illustrate overall 1-year survival rates. RESULTS: Liver metastases showed significant differences in AP before and after transarterial radioembolization in responders (P < .05) but not in nonresponders (P = .164). In HCC, AP values before and after transarterial radioembolization were not significantly different in responders and nonresponders (P = .180 and P = .052). Tumor diameters were not significantly different on CT perfusion before and after transarterial radioembolization in responders and nonresponders with liver metastases and HCC (P = .654, P = .968, P = .148, P = .164). In patients with significant decrease of AP in liver metastases after transarterial radioembolization, 1-year overall survival was significantly higher than in patients showing no reduction of AP. CONCLUSIONS: CT perfusion showed early reduction of AP in liver metastases responding to transarterial radioembolization; tumor diameter remained unchanged early after treatment. No significant early treatment response to transarterial radioembolization was found in patients with HCC. In patients with liver metastases, a decrease of AP after transarterial radioembolization was associated with a higher 1-year overall survival rate.

Tumor imaging in patients with advanced tumors using a new (99m) Tc-radiolabeled vitamin B12 derivative.

UNLABELLED: Targeting cancer cells with vitamin B12 (cobalamin) is hampered by unwanted physiologic tissue uptake mediated by transcobalamin. Adhering to good manufacturing practice, we have developed a new (99m)Tc-cobalamin derivative ((99m)Tc(CO)3-[(4-amido-butyl)-pyridin-2-yl-methyl-amino-acetato] cobalamin, (99m)Tc-PAMA-cobalamin). The derivative shows no binding to transcobalamin but is recognized by haptocorrin, a protein present in the circulation and notably expressed in many tumor cells. In this prospective study, we investigated cancer-specific uptake of (99m)Tc-PAMA-cobalamin in 10 patients with various metastatic tumors. METHODS: Ten patients with biopsy-proven metastatic cancer were included. Dynamic imaging was started immediately after injection of 300-500 MBq of (99m)Tc-PAMA-cobalamin, and whole-body scintigrams were obtained at 10, 30, 60, 120, and 240 min and after 24 h. The relative tumor activity using SPECT/CT over the tumor region after 4 h was measured in comparison to disease-free lung parenchyma. Patients 3-10 received between 20 and 1,000 µg of cobalamin intravenously before injection of (99m)Tc-PAMA-cobalamin. The study population comprised 4 patients with adenocarcinomas of the lung, 3 with squamous cell carcinomas of the hypopharyngeal region, 1 with prostate adenocarcinoma, 1 with breast, and 1 with colon adenocarcinoma. RESULTS: The median age of the study group was 61 ± 11 y. Six of 10 patients showed positive tumor uptake on (99m)Tc-PAMA-cobalamin whole-body scintigraphy. The scan was positive in 1 patient with colon adenocarcinoma, in 3 of 4 lung adenocarcinomas, in 1 of 3 hypopharyngeal squamous cell carcinomas, and in 1 breast adenocarcinoma. Renal uptake was between 1% and 3% for the left kidney. Predosing with cobalamin increased the tumor uptake and improved blood-pool clearance. The best image quality was achieved with a predose of 20-100 ug of cold cobalamin. The mean patient dose was 2.7 ± 0.9 mSv/patient. CONCLUSION: To our knowledge, we report for the first time on (99m)Tc-PAMA-cobalamin imaging in patients with metastatic cancer disease and show that tumor targeting is feasible.

Computed tomographic perfusion imaging for the prediction of response and survival to transarterial radioembolization of liver metastases.

PURPOSE: The purpose of this study was to evaluate prospectively, in patients with liver metastases, the ability of computed tomographic (CT) perfusion to predict the morphologic response and survival after transarterial radioembolization (TARE). METHODS: Thirty-eight patients (22 men; mean [SD] age, 63 [12] years) with otherwise therapy-refractory liver metastases underwent dynamic, contrast-enhanced CT perfusion within 1 hour before treatment planning catheter angiography, for calculation of the arterial perfusion (AP) of liver metastases, 20 days before TARE with Yttrium-90 microspheres. Treatment response was evaluated morphologically on follow-up imaging (mean, 114 days) on the basis of the Response Evaluation Criteria in Solid Tumors criteria (version 1.1). Pretreatment CT perfusion was compared between responders and nonresponders. One-year survival was calculated including all 38 patients using the Kaplan-Meier curves; the Cox proportional hazard model was used for calculating predictors of survival. RESULTS: Follow-up imaging was not available in 11 patients because of rapidly deteriorating health or death. From the remaining 27, a total of 9 patients (33%) were classified as responders and 18 patients (67%) were classified as nonresponders. A significant difference in AP was found on pretreatment CT perfusion between the responders and the nonresponders to the TARE (P < 0.001). Change in tumor size on the follow-up imaging correlated significantly and negatively with AP before the TARE (r = -0.60; P = 0.001). Receiver operating characteristics analysis of AP in relation to treatment response revealed an area under the curve of 0.969 (95% confidence interval, 0.911-1.000; P < 0.001). A cutoff AP of 16 mL per 100 mL/min was associated with a sensitivity of 100% (9/9) (95% CI, 70%-100%) and a specificity of 89% (16/18) (95% CI, 62%-96%) for predicting therapy response. A significantly higher 1-year survival after the TARE was found in the patients with a pretreatment AP of 16 mL per 100 mL/min or greater (P = 0.028), being a significant, independent predictor of survival (hazard ratio, 0.101; P = 0.015). CONCLUSIONS: Arterial perfusion of liver metastases, as determined by pretreatment CT perfusion imaging, enables prediction of short-term morphologic response and 1-year survival to TARE.