Nuclear Medicine

Distribution of bone tracer uptake in symptomatic knees after ACL reconstruction compared to asymptomatic non-operated knees: a method for better differentiating patient-specific from disease-specific bone tracer uptake in SPECT/CT Abstract Objective To evaluate the differences of bone tracer uptake (BTU) in symptomatic and asymptomatic contralateral knees in patients after reconstruction of the anterior cruciate ligament (ACL-R) and to identify typical BTU patterns and threshold values to differentiate pathological from physiological BTU. Methods 53 patients after unilateral ACL-R were retrospectively included in the study. The population was subdivided into a group of symptomatic operated knees and a group of contralateral asymptomatic non-operated knees. BTU was measured in SPECT/CT using a validated anatomical localization-scheme and normalized mean BTU values were calculated in both knees. Wilcoxon signed rank-test and Pearson's rank-correlation coefficient were used (p < 0.05). Results Symptomatic knees after ACL-R showed significantly more BTU than asymptomatic ones (p < 0.01).Based on the measured BTU activity in SPECT/CT in symptomatic operated and asymptomatic non-operated knees, intensity thresholds of pathological BTU were established. A BTU threshold of greater than the Median + 1 SD of the asymptomatic non-operated knee was defined as pathological. In both groups the highest mean BTU was found on the femoral, tibial and patellar articular surfaces, the lowest BTU in femoral and tibial regions far from the joint. Conclusions The established BTU thresholds for SPECT/CT in knees after ACL-R help to differentiate disease-specific from patient-specific BTU. It could be speculated that BTU in asymptomatic knees equates to the preoperative condition of the knee joint before ACL-R. Therefore, the results of this study help to understand in-vivo loading of the knee and ultimately lead to prediction of development of osteoarthritis in an early stage.

18 F-DOPA uptake does not correlate with IDH mutation status and 1p/19q co-deletion in glioma Abstract Objective The role of amino acid positron emission tomography (PET) in glioma grading and outcome prognostication has not yet been well established. This is particularly true in the context of the new WHO 2016 classification, which introduced a definition of glioma subtypes primarily based on molecular fingerprints. The aim of the present study was to correlate 3,4‑dihydroxy‑6‑[18F]‑fluoro-l‑phenylalanine (F-DOPA) uptake parameters with IDHmutation, 1p/19q status, and survival outcomes in patients with glioma. Methods The study population consisted of 33 patients (17 M/16 F, mean age: 46 ± 13 years) who underwent F-DOPA PET/CT for the evaluation of tumor extent before the start of chemo or radiotherapy. The presence of IDHmutation and 1p/19q status was assessed in all the cases. Tumor volume and semiquantitative uptake parameters, namely SUVmax, tumor-to-normal brain ratio and tumor-to-normal striatum ratio, were calculated for each tumor. Imaging-derived parameters were compared between patients stratified according to molecular fingerprints, using parametric or non-parametric tests, where appropriate. The Kaplan–Meier method was used to assess differences of overall survival (OS) and progression-free survival (PFS) between groups. PET parameters were also tested as prognostic factors in univariate Cox survival regression models. Results There were 12 IDH-wild-type and 21 IDH-mutant patients. Stratification according to 1p/19q co-deletion resulted in 20 non-co-deleted and 13 co-deleted patients. Median follow-up time from PET/CT exam was 30.5 months (range 3.5–74 months). Semiquantitative uptake parameters did correlate neither with IDH mutation nor with 1p/19q status. Uptake was similar in low-grade and high-grade tumors, respectively. In addition, F-DOPA uptake parameters, macroscopic tumor volume, or tumor grade did not stratify OS, while a correlation between SUVmax and PFS was shown in the subgroup of astrocytomas. On the other hand, IDH mutation status and presence of 1p/19q co-deletion had a significant impact on survival outcomes. The prognostic value of IDH mutation status was also confirmed in the subgroup of patients with astrocytic tumors. Conclusions F-DOPA uptake parameters do not correlate with tumor molecular and histological characteristics. The predictive value of PET-derived parameters on outcomes of survival is limited.

Fundamental study of radiogallium-labeled aspartic acid peptides introducing octreotate derivatives Abstract Objective Somatostatin receptors are highly expressed in neuroendocrine tumors, and many radiolabeled somatostatin analogs for diagnosis and treatment have been developed. To simultaneously detect not only primary cancer but also bone metastases, this study aimed to develop a positron emission tomography probe using generator-produced nuclide Gallium-68 (T1/2 = 68 min), in which a carrier for primary cancer, a carrier for bone metastases lesions, and a stable gallium complex are introduced into the one molecule. Based on this strategy, the somatostatin receptor-targeted peptide, [Tyr3]-octreotate (TATE), aspartic acid peptide (Dn) with high binding affinity for hydroxyapatite, and Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as a stable gallium complex were selected. The novel complexes, Ga-DOTA-Dn-TATE (n = 0, 2, 5, 8, or 11), were designed, synthesized, and evaluated. The radiogallium complexes were prepared using the easy-to-handle radioisotope 67Ga due to relatively long half-life. Methods The radiogallium complex precursor DOTA-Dn-TATE was synthesized by the Fmoc-based solid-phase method and by the air oxidation method to form the disulfide bond. [67Ga]Ga-DOTA-Dn-TATE was synthesized by reacting DOTA-Dn-TATE and 67Ga. Hydroxyapatite binding assays, in vitro cellular uptake experiments in AR42J tumor cells, in biodistribution experiments in AR42J tumor-bearing mice, were performed using [67Ga]Ga-DOTA-Dn-TATE. Results The radiochemical purities of [67Ga]Ga-DOTA-Dn-TATE were > 96.0%. In in vitro and in vivo experiments, [67Ga]Ga-DOTA-D11-TATE had a high affinity for hydroxyapatite and highly accumulated in bone. However, the uptake of [67Ga]Ga-DOTA-D11-TATE into somatostatin receptor-positive AR42J cells was lower than that of [67Ga]Ga-DOTA-TATE, and the accumulation of [67Ga]Ga-DOTA-D11-TATE in tumor was significantly low. Conclusion Ga-DOTA-D11-TATE may not be recognized by somatostatin receptor by the introduction of D11, and the charge adjustment may be important for somatostatin receptor-positive cell uptake.

Brain 18 F-FDG distribution: which region is most affected by increased plasma glucose levels?

Clinical feasibility of early scanning after administration of 68 Ga-DOTATOC Abstract Objective Positron emission tomography (PET)/computed tomography (CT) using 68Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-d-Phe1-Tyr3-octreotide (DOTATOC) is usually performed about 1-h post-injection; however, because of rapid blood clearance, the waiting time for scanning could possibly be shortened without affecting diagnostic performance. The purpose of this study was to investigate the feasibility of early scanning at 30 min post-injection. Methods Thirty-eight patients who underwent DOTATOC-PET/CT were analyzed. After administration of 68Ga-DOTATOC, data acquisition was performed twice, at 30-min and 60-min post-injection. The number of known or suspected pathological lesions, and quantitative values of those lesions and physiological uptake were compared. SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion uptake (TLU) were calculated as quantitative values of the pathological lesions. Results A total of 125 known or suspected pathological lesions were found at both timepoints, with no differences between the two datasets. The SUVmax, SUVpeak, MTV, and TLU were highly reproducible, with Spearman's ρ of 0.983, 0.986, 0.918, and 0.981, respectively. The average percent differences (%DIFFave) defined as the differences of the values divided by the value at 1-h post-injection were 11.1% for SUVmax, 8.5% for SUVpeak, 15.1% for MTV, and 20.6% for TLU. Physiological uptake in the two datasets was closely comparable in the pituitary gland (Spearman's ρ = 0.954, %DIFFave = 11.0%), liver (0.989, 3.9%), spleen (0.970, 6.3%), adrenal glands (0.879, 13.0%), and pancreatic uncus (0.946, 12.7%). Conclusion The diagnostic performance of visual interpretation should be comparable between DOTATOC-PET/CT images obtained at 30-min and 60-min post-injection. Some differences between quantitative values may exist; however, they appear to be minimal.

Techniques for generating attenuation map using cardiac SPECT emission data only: a systematic review Abstract To reliably interpret and perform quantitative analysis, attenuation correction for cardiac single-photon emission computed tomography (SPECT) is fundamental. Thus, knowledge of the patient-specific attenuation map for accurate correction is required in SPECT quantitative imaging. The aim of this systematic review is to present general principles of attenuation correction and provide a structured summary of the approaches that have been proposed for generating the attenuation map for cardiac SPECT. We identified relevant articles published in English pertaining to the attenuation map (AM) determination using SPECT emission data only by searching PubMed, EMBASE, Scopus, and Web of Science databases. Moreover, other articles were hand searched. The protocol of this systematic review was registered in PROSPERO and the code given is CRD42017060512. Transmissionless techniques of determining attenuation map including calculated methods, statistical modeling for simultaneous estimation of attenuation and emission, consistency conditions criteria, using scattered data and other methods were reviewed. Methods for performing attenuation map for cardiac SPECT are developing and the progresses made are promising. However, much work is needed to assess the efficacy of the correction schemes in the clinical routine.

The significant value of predicting prognosis in patients with colorectal cancer using 18 F-FDG PET metabolic parameters of primary tumors and hematological parameters Abstract Objects The purpose was to evaluate the correlation of the pre-treatment hematological parameters with metabolic parameters of primary tumor in baseline 18F-FDG PET/CT in patients with colorectal cancer (CRC) and estimate the prognostic value of both. Methods We retrospectively investigated 231 patients with CRC who underwent baseline 18F-FDG PET/CT. Routine blood sampling was tested in the same term. PET parameters in term of hematological parameters and pathological characteristics of primary tumor were compared. Kaplan–Meier survival analysis was performed in the patients without distant metastasis. The differences of disease-free survival between groups were compared by log-rank tests. Results Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were significantly correlated with all the metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG). The patients with NLR > 3 had higher MTV (24.82 ± 18.16 vs 19.06 ± 13.30, P = 0.039) and TLG (219.04 ± 186.94 vs 166.45 ± 146.39, P = 0.047) than those whose NLR ≤ 3. NLR in those patients with distant metastasis was significantly higher than those without distant metastasis (P = 0.018) while LMR in those patients with distant metastasis was significantly lower than those without distant metastasis (P = 0.032). Survival analysis showed that those patients with low MTV (P = 0.015), low NLR (P = 0.008) and high LMR (P = 0.027) revealed significant survival benefit. Conclusions There was a significant association between the pre-treatment hematological parameters and metabolic parameters of baseline 18F-FDG PET/CT in the patients with CRC. It might be helpful in those patients with high NLR and low LMR to undergo 18F-FDG PET/CT to detect distant metastasis and predict prognosis.

Comparison of 18 F-Choline PET/CT and MRI functional parameters in prostate cancer Abstract Aim 18F-Choline (FCH) uptake parameters are strong indicators of aggressive disease in prostate cancer. Functional parameters derived by magnetic resonance imaging (MRI) are also correlated to aggressive disease. The aim of this work was to evaluate the relationship between metabolic parameters derived by FCH PET/CT and functional parameters derived by MRI. Materials and methods Fourteen patients with proven prostate cancer who underwent FCH PET/CT and multiparametric MRI were enrolled. FCH PET/CT consisted in a dual phase: early pelvic list-mode acquisition and late whole-body acquisition. FCH PET/CT and multiparametric MRI examinations were registered and tumoral volume-of-interest were drawn on the largest lesion visualized on the apparent diffusion coefficient (ADC) map and projected onto the different multiparametric MR images and FCH PET/CT images. Concerning the FCH uptake, kinetic parameters were extracted with the best model selected using the Akaike information criterion between the one- and two-tissue compartment models with an imaging-derived plasma input function. Other FCH uptake parameters (early SUVmean and late SUVmean) were extracted. Concerning functional parameters derived by MRI scan, cell density (ADC from diffusion weighting imaging) and vessel permeability (Ktrans and Ve using the Tofts pharmakinetic model from dynamic contrast-enhanced imaging) parameters were extracted. Spearman's correlation coefficients were calculated to compare parameters. Results The one-tissue compartment model for kinetic analysis of PET images was selected. Concerning correlation analysis between PET parameters, K1 was highly correlated with early SUVmean (r = 0.83, p < 0.001) and moderately correlated with late SUVmean (r = 0.66, p = 0.010) and early SUVmean was highly correlated with late SUVmean (r = 0.90, p < 0.001). No significant correlation was found between functional MRI parameters. Concerning correlation analysis between PET and functional MRI parameters, K1 (from FCH PET/CT imaging) was moderately correlated with Ktrans (from perfusion MR imaging) (r = 0.55, p = 0.041). Conclusions No significant correlation was found between FCH PET/CT and multiparametric MRI metrics except FCH influx which is moderately linked to the vessel permeability in prostate cancer.

Count-based method for specific binding ratio calculation in [I-123]FP-CIT SPECT analysis Abstract Objective To calculate the specific binding ratio (SBR) appropriately in dopamine transporter (DAT) imaging, a method for extracting the striatal volume of interest (VOI) was developed. Methods This study included 200 patients (72 ± 10 years) who were suspected of parkinsonian syndromes (PS) or dementia with Lewy body (DLB). The patients were divided into three groups of PS with dopaminergic degeneration, DLB and non-PS after [123I]ioflupane (FP-CIT) SPECT and clinical follow-up. The image data were reconstructed with CT attenuation correction and scatter correction, and with only CT attenuation correction (CTAC). The new method extracted striatal VOI according to the high-level counts and the average striatum volume, and calculated SBR using the reference occipital counts. The SBR values for each patient were obtained using the Tossici-Bolt method (SBRBolt) and our method. Reproducibility of SBR calculation using our method was compared by two operators. Results The mean SBR values for the PS and DLB groups were significantly different from that of the non-PS group with both methods. The coefficients of variation of the SBR were significantly smaller with the proposed method compared with those of SBRBolt (p < 0.001), except for the CTAC images. There were no differences in SBR between the two operators using our method. The diagnostic accuracies with our method for the PS and DLB groups were 98.4 and 96.0%, respectively. Conclusion Our new method for SBR calculation in the FP-CIT SPECT showed less coefficients of variation with high reproducibility, which would be useful for clinical diagnosis and in assessing the severity of diseases in follow-up studies.

The role of 13 N -ammonia in the differential diagnosis of gliomas and brain inflammatory lesions Abstract Objective To investigate the utility of 13N-ammonia PET/CT imaging in the differential diagnosis of gliomas and brain inflammations. Methods 13N-ammonia PET/CT imaging data of 77 patients with gliomas and 34 patients with brain inflammations were retrospectively analyzed. No patients received any treatment before 13N-ammonia imaging. All the patients were diagnosed by stereotactic biopsy or clinical follow-up. Visual and semi-quantitative analysis was performed to analyze the results of 13N-ammonia imaging. Finally, the uptake ratios of each lesion were calculated and its differences among different groups were tested with one-way ANOVA. Results 29.4% inflammations, 51.6% low-grade gliomas and 91.3% high-grade gliomas were positive by visual analysis in 13N-ammonia imaging. The sensitivity, specificity and accuracy for the diagnosis of gliomas were 75.3%, 55.8% and 67.8%, respectively. As for semi-quantitative analysis, the T/G ratios of inflammatory lesions, low-grade gliomas and high-grade gliomas were 0.88 ± 0.24, 1.04 ± 0.43 and 1.43 ± 0.49, respectively. One-way ANOVA revealed that the T/G ratios of high-grade gliomas were significantly higher than those of low-grade gliomas and inflammations (P < 0.05), but there was no statistical difference between low-grade gliomas and inflammations (P = 0.118). Among the inflammatory lesions, T/G ratios were not statistically different between infectious and demyelinating lesions (P > 0.05). ROC curve analysis showed that the optimal cut-off value of T/Gratio in distinguishing gliomas from inflammations was 1.21 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 52.9%, 94.4%, 65.3%, 95.7% and 45.9%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas was 1.06 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 81.5%, 67.7%, 76.5%, 81.5% and 67.7%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas and inflammations was 1.19 with the AUC 0.84. The sensitivity, specificity, accuracy, PPV and NPV were 70.4%, 85.1%, 78.5%, 79.2% and 78.1%, respectively. Conclusions 13N-ammonia imaging is effective in distinguishing high-grade gliomas from low-grade gliomas and inflammations, but its role in the differential diagnosis of low-grade gliomas and brain inflammatory lesions is limited, and the accuracy needs to be improved.