Correlations between plasma and PET beta-amyloid levels in individuals with subjective cognitive decline: the Fundació ACE Healthy Brain Initiative (FACEHBI).

BACKGROUND: Peripheral biomarkers that identify individuals at risk of developing Alzheimer's disease (AD) or predicting high amyloid beta (Aß) brain burden would be highly valuable. To facilitate clinical trials of disease-modifying therapies, plasma concentrations of Aß species are good candidates for peripheral AD biomarkers, but studies to date have generated conflicting results. METHODS: The Fundació ACE Healthy Brain Initiative (FACEHBI) study uses a convenience sample of 200 individuals diagnosed with subjective cognitive decline (SCD) at the Fundació ACE (Barcelona, Spain) who underwent amyloid florbetaben(18F) (FBB) positron emission tomography (PET) brain imaging. Baseline plasma samples from FACEHBI subjects (aged 65.9 ± 7.2 years) were analyzed using the ABtest (Araclon Biotech). This test directly determines the free plasma (FP) and total plasma (TP) levels of Aß40 and Aß42 peptides. The association between Aß40 and Aß42 plasma levels and FBB-PET global standardized uptake value ratio (SUVR) was determined using correlations and linear regression-based methods. The effect of the APOE genotype on plasma Aß levels and FBB-PET was also assessed. Finally, various models including different combinations of demographics, genetics, and Aß plasma levels were constructed using logistic regression and area under the receiver operating characteristic curve (AUROC) analyses to evaluate their ability for discriminating which subjects presented brain amyloidosis. RESULTS: FBB-PET global SUVR correlated weakly but significantly with Aß42/40 plasma ratios. For TP42/40, this observation persisted after controlling for age and APOE ε4 allele carrier status (R2 = 0.193, p = 1.01E-09). The ROC curve demonstrated that plasma Aß measurements are not superior to APOE and age in combination in predicting brain amyloidosis. It is noteworthy that using a simple preselection tool (the TP42/40 ratio with an empirical cut-off value of 0.08) optimizes the sensitivity and reduces the number of individuals subjected to Aß FBB-PET scanners to 52.8%. No significant dependency was observed between APOE genotype and plasma Aß measurements (p value for interaction = 0.105). CONCLUSION: Brain and plasma Aß levels are partially correlated in individuals diagnosed with SCD. Aß plasma measurements, particularly the TP42/40 ratio, could generate a new recruitment strategy independent of the APOE genotype that would improve identification of SCD subjects with brain amyloidosis and reduce the rate of screening failures in preclinical AD studies. Independent replication of these findings is warranted.

Correlation of 18F-FDG uptake on PET/CT with Ki67 immunohistochemistry in pre-treatment epithelial ovarian cancer. / Correlación de la captación de 18F-FDG de la PET/TC con el Ki67 de la inmunohistoquímica en el cáncer epitelial de ovario pretratamiento.

OBJECTIVE: Standardised uptake value (SUV) and volumetric parameters such as metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from 18F-FDG PET/CT are useful criteria for disease prognosis in pre-operative and post-treatment epithelial ovarian cancer (EOC). Ki67 is another prognostic biomarker in EOC, associated with tumour aggressiveness. The aim of this study is to evaluate the association between 18F-FDG PET/CT measurements and Ki67 in pre-treatment EOC to determine if PET/CT parameters could non-invasively predict tumour aggressiveness. MATERIAL AND METHODS: A pre-treatment PET/CT was performed on 18 patients with suspected or newly diagnosed EOC. Maximum SUV (SUVmax), mean SUV (SUVmean), whole-body MTV (wbMTV), and whole-body TLG (wbTLG) with a threshold of 30% and 40% of the SUVmax were obtained. Furthermore, Ki67 index (mean and hotspot) was estimated in tumour tissue specimens. Immunohistochemical findings were correlated with PET parameters. RESULTS: The mean age was 57.0 years old (standard deviation 13.6 years). A moderate correlation was observed between mean Ki67 index and SUVmax (r=0.392), SUVmean 30% (r=0.437), and SUVmean 40% (r=0.443), and also between hotspot Ki67 index and SUVmax (r=0.360), SUVmean 30% (r=0.362) and SUVmean 40% (r=0.319). There was a weaker correlation, which was inversely negative, between mean and hotspot Ki67 and volumetric PET parameters. However, no statistical significant differences were found for any correlations. CONCLUSIONS: SUVmax and SUVmean were moderately correlated with Ki67 index, whereas volumetric PET parameters overall, showed a weaker correlation. Thus, SUVmax and SUVmean could be used to assess tumour aggressiveness in pre-treatment EOC.

18F-FDG PET/CT and sentinel lymph node biopsy in the staging of patients with cervical and endometrial cancer. Role of dual-time-point imaging.

OBJECTIVE: Definitive staging for cervical (CC) and endometrial cancer (EC) takes place once surgery is performed. The aim of this study was to evaluate the role of PET/CT in detecting lymphatic metastasis in patients with CC and EC using dual-time-point imaging (DPI), taking the histopathological results of sentinel lymph node (SLN) and lymphadenectomy as the reference. MATERIAL AND METHODS: A prospective study was conducted on 17 patients with early CC, and 13 patients with high-risk EC. The patients had a pre-operative PET/CT, MRI, SLN detection, and lymphadenectomy, when indicated. PET/CT findings were compared with histopathological results. RESULTS: In the pathology study, 4 patients with CC and 4 patients with EC had lymphatic metastasis. PET/CT showed hypermetabolic nodes in 1 patient with CC, and 5 with EC. Four of these had metastasis, one detected in the SLN biopsy. Four patients who had negative PET/CT had micrometastasis in the SLN biopsy, 1 patient with additional lymph nodes involvement. The overall patient-based sensitivity, specificity, positive and negative predictive values, and accuracy of PET/CT to detect lymphatic metastasis was 20.0%, 100.0%, 100.0%, 87.9%, and 88.2%, respectively, in CC, and 57.1%, 88.9%, 66.7%, 84.2% and 80.0%, respectively, in EC. DPI showed higher retention index in malignant than in inflammatory nodes, although no statistically significant differences were found. CONCLUSIONS: PET/CT has low sensitivity in lymph node staging of CC and EC, owing to the lack of detection of micrometastasis. Thus, PET/CT cannot replace SLN biopsy. Although no statistically significant differences were found, DPI may help to differentiate between inflammatory and malignant nodes.

Dual time-point (18)F-FDG PET/CT to assess response to radiofrequency ablation of lung metastases.

AIM: To establish the usefulness of dual time-point PET/CT imaging in determining the response to radiofrequency ablation (RFA) of solitary lung metastases from gastrointestinal cancer. MATERIALS AND METHODS: This prospective study included 18 cases (3 female, 15 male, mean age 71±15 yrs) with solitary lung metastases from malignant digestive tract tumors candidates for RFA. PET/CT images 1h after injection of 4.07MBq/kg of (18)F-FDG (standard images) were performed at baseline, 1 month, and 3 months after RFA. PET/CT images 2h after injection centered in the thorax at 1 month after RFA were also performed (delayed images). A retention index (RI) of dual time-point images was calculated as follows: RI=(SUVmax delayed image-SUVmax standard image/SUVmax standard image)*100. Pathological confirmation of residual tumor by histology of the treated lesion was considered as local recurrence. A negative imaging follow-up was considered as complete response. RESULTS: Local recurrence was found in 6/18 lesions, and complete response in the remaining 12. The mean percentage change in SUVmax at 1 month and at 3 months showed a sensitivity and specificity for PET/CT of 50% and 33%, and 67% and 92%, respectively. The RI at 1 month after RFA showed a sensitivity and specificity of 83% and 92%, respectively. CONCLUSIONS: Dual time point PET/CT can predict the outcome at one month after RFA in lung metastases from digestive tract cancers. The RI can be used to indicate the need for further procedures to rule out persistent tumor due to incomplete RFA.

Prognostic value of (18)F-FDG PET/CT volumetric parameters in recurrent epithelial ovarian cancer.

OBJECTIVE: Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in various solid neoplasms. These volumetric parameters and the SUVmax have shown to be useful criteria for disease prognostication in preoperative and post-treatment epithelial ovarian cancer (EOC) patients. The purpose of this study was to evaluate the utility of (18)F-FDG PET/CT measurements to predict survival in patients with recurrent EOC. MATERIAL AND METHODS: Twenty-six patients with EOC who underwent a total of 31 (18)F-FDG PET/CT studies for suspected recurrence were retrospectively included. SUVmax and volumetric parameters whole-body MTV (wbMTV) and whole-body TLG (wbTLG) with a threshold of 40% and 50% of the SUVmax were obtained. Correlation between PET parameters and progression-free survival (PFS) and the survival analysis of prognostic factors were calculated. RESULTS: Serous cancer was the most common histological subtype (76.9%). The median PFS was 12.5 months (range 10.7-20.6 months). Volumetric parameters showed moderate inverse correlation with PFS but there was no significant correlation in the case of SUVmax. The correlation was stronger for first recurrences. By Kaplan-Meier analysis and log-rank test, wbMTV 40%, wbMTV 50% and wbTLG 50% correlated with PFS. However, SUVmax and wbTLG 40% were not statistically significant predictors for PFS. CONCLUSION: Volumetric parameters wbMTV and wbTLG 50% measured by (18)F-FDG PET/CT appear to be useful prognostic predictors of outcome and may provide valuable information to individualize treatment strategies in patients with recurrent EOC.

11C-Choline PET/CT in the primary diagnosis of prostate cancer: impact on treatment planning.

AIM: Aim of the present study was to evaluate the usefulness of 11C-choline PET/CT for detecting lymphatic or haematogenous spread and for planning radiotherapy in patients with medium-to-high risk prostate cancer. METHODS: We have included 61 consecutive patients recently diagnosed with cancer prostate by biopsy. All patients were classified as medium-to-high risk: Gleason: 7-9; PSA: 6.3-30.4 ng/mL; stage T2c (N.=20) or stage T3 (N.=41). Image acquisition began 5 min after intravenous injection of 11C-choline (656+119 MBq), starting at the pelvis and continuing craniocaudally. Images were interpreted visually to evaluate uptake by the prostate gland. Lymph nodes with 11C-choline uptake were considered invaded, regardless of their size. Bone lesions were considered positive when they showed greater focal uptake than the surrounding bone. In patients with evidence of lymph-node invasion or bone metastases (15 patients), disease was classified as locoregional, oligometastatic, or multimetastatic. RESULTS: All patients had prostate gland uptake (20 focal, 8 bifocal, and 33 multifocal). Extraprostatic disease was present in 15 patients (24.6%), as follows: 9 (60%) in a single location: in an infradiaphragmatic lymph node (N.=6), in a supradiaphragmatic lymph node (N.=1), and in bone (M1) (N.=2). Six (40%) as multifocal invasion: with both infra- and supradiaphragmatic lymph node involvement (N.=2); with infradiaphragmatic lymph node involvement and M1 bone metastases (N.=3); and infra- and supradiaphragmatic lymph node involvement plus M1 bone metastases (N.=1). Disease was classified as locoregional (N.=6), oligometastatic (N.=5), and multimetastatic (N.=4). The 11 (73.3%) patients with locoregional and oligometastatic disease were selected to undergo intensity-modulated radiation therapy with dose escalation based on the PET findings. CONCLUSION: Our results suggest that 11C-choline PET/CT is a useful one-stop diagnostic procedure for evaluating patients with medium/high risk prostate cancer scheduled for radical treatment. 11C-choline PET/CT can reliably rule out lymph node involvement and remote metastases, allowing to select candidates for radiotherapy and to plan their treatment.

[PET and SPECT in epilepsy]. / PET y SPECT en la epilepsia.

Epilepsy is one of the most frequent chronic neurological disorders, affecting 1-2% of the population. Patients with complex partial drug resistant episodes may benefit from a surgical treatment consisting in the excision of the epileptogenic area. Localization of the epileptogenic area was classically performed with video-EEG and magnetic resonance (MR). Recently, functional neuroimaging studies of Nuclear Medicine, positron emission tomography (PET) and single photon emission tomography (SPECT) have demonstrated their utility in the localization of the epileptogenic area prior to surgery. Ictal SPECT with brain perfusion tracers show an increase in blood flow in the initial ictal focus, while PET with (18)FDG demonstrates a decrease of glucose metabolism in the interictal functional deficit zone. In this review, the basic principles and methodological characteristics of the SPECT and PET in epilepsy are described. The ictal SPECT injection mechanism, different patterns of perfusion based on the time of ictal, postictal or interictal injection are detailed and the different diagnostic sensitivities of each one of these SPECT are reviewed. Different methods of analysis of the images with substraction and fusion systems with the MR are described. Similarly, the injection methodology, quantification and evaluation of the images of the PET in epilepsy are described. Finally, the main clinical indications of SPECT and PET in temporal and extratemporal epilepsy are detailed.

[Metabolic and osteogenic pattern of prostate cancer bone metastases]. / Perfil metabólico y osteogénico de las metástasis óseas por cáncer de próstata.

The current protocols include the bone scintigraphy and choline PET/CT to localize recurrence in patients having elevated serum PSA after treatment for prostate cancer. Both methods show good agreement in the diagnosis of bone metastases, however conflicting results can be found. We present three cases in which a PET/CT was performed with (18)F-Fluoride due to disagreement between the bone scintigraphy and (11)C-Choline PET/CT. The (18)F-Fluoride PET/CT was capable of confirming the existence of bone metastasis in all of them, so it may be an alternative to the MRI as a tracer of second bone imaging modality, although its use is limited by cost and availability.

PET/CT with [18F] fluorodeoxyglucose in the assessment of metabolic response to neoadjuvant chemotherapy in locally advanced breast cancer.

AIM: The aim of this paper was to prospectively evaluate FDG PET/CT in the assessment of metabolic response to neoadjuvant chemotherapy and correlation with tumor cellularity in locally advanced breast cancer. METHODS: Images were acquired with a PET/CT scanner in 50 patients at baseline and after completion of treatment, just before surgery. All findings were confirmed by histopathological analysis. PET/CT quantification (SUVmax) at baseline and after finishing neoadjuvant chemotherapy (4 cycles of epirubicin + cyclophosphamide +/- taxanes) were compared using RECIST criteria and Miller & Payne (M&P) scale. RESULTS: Baseline mean tumor size was 4.4±1.6 cm. Thirty eight patients were considered responders and 12 nonresponders. According to M&P scale, 10 patients had good prognosis (grades 4-5) and 40 patients had bad prognosis (grades 1-3). All patients with grade 5 M&P had no significant postchemotherapy FDG uptake. Patients with bad prognosis had lower SUVmax variation (∆SUVmax) than patients with good prognosis (60.7% vs. 80.5%, P=0.0016). ∆SUVmax was lower in nonresponders than in partial responders according to RECIST criteria (38.9% vs. 67.6%, p<0.001), and was also lower in partial responders than complete responders (67.6% vs. 85.4%, P=0.005). A cut-off ∆SUVmax value of 52% differentiates responders from nonresponders with a sensitivity of 86% and a specificity of 90%. Probability densities of the ∆SUVmax (%) for stable disease (<45), partial (>45 to <82) and complete response (>82) showed an overall accuracy of 78% (Weighted Kappa=0.74). CONCLUSION: PET/CT is useful to monitor response to neoadjuvant chemotherapy in locally advanced breast cancer. ∆SUVmax on PET/CT correlates with tumor cellularity after completion of neoadjuvant chemotherapy.

[Dual-time point images of the liver with (18)F-FDG PET/CT in suspected recurrence from colorectal cancer]. / (18)F-FDG PET/TC con imagen hepática en dos tiempos en la sospecha de recidiva del cáncer colorrectal

AIM: To analyze the potential improvement of (18)F-fluorodeoxyglucose (FDG) PET/CT using additional delayed images of the liver in operated colorectal cancer. MATERIAL AND METHODS: The study prospectively included 71 patients (22 women, 49 men) with mean age of 65 ± 11 years with clinical, analytic or radiological suspicion of current disease. A whole body PET/CT scan was performed at 60 min. (standard images) and after 2 hr (delayed images) post-injection of 4.07 MBq/Kg of (18)F-FDG. Visual and quantitative SUV analysis of PET/CT findings was done. All findings were confirmed by histopathology and/or at least 6 months follow-up. RESULTS: Thirty-seven out of 71 patients were diagnosed of liver metastases (79 metastases). In 38/71 cases there was extra-hepatic disease in the form of local recurrence (10), abdominopelvic (3) or mediastinal (3) lymph nodes, bone (1) or lung metastases (16) and carcinomatosis (10). Sensitivity and specificity in the diagnosis of liver metastases in a patient-by-patient basis in standard (81% and 91%) and in delayed images (95% y 97%) was calculated. The number of lesions detected in delayed images was significantly higher (66/79) than in standard images (57/79). Sensitivity and specificity for PET/CT in the diagnosis of extra-hepatic disease was 84% and 70%, contributing to the detection of synchronous tumors in 5 patients. CONCLUSIONS: PET/CT may be useful in the diagnosis of extra-hepatic disease in suspected recurrence of colorectal cancer. Delayed images on PET/CT may increase the sensitivity to identify liver metastases.

[PET/CT-guided salvage surgery protocol. Results with ROLL Technique and PET probe]. / Protocolo de cirugía de rescate guiada por PET/TAC. Resultados con técnica ROLL y sonda PET.

OBJECTIVE: To assess the value of intraoperatory radioguided probe detection to guide surgical resection of malignant lesions previously detected by (18)F-FDG PET-CT. MATERIAL: Twelve consecutive patients with suspected tumor recurrence detected by (18)F-FDG PET-CT considered resectable were enrolled in the study. Ultrasound guided fine needle aspiration (FNA) before surgery was performed in 6 patients and CT guided biopsy was performed in 1 patient. In 5 patients with accessible lesions, a radioguided occult lesion localization (ROLL) technique was performed after injection of (99m)Tc-colloid (1.7-2.4 mCi) inside the lesion under ultrasound or CT guidance, pre-operatively. Radioguided surgical detection was then carried out 19-24 hours afterwards using the gamma probe. In 7 patients with non-accessible needle lesions or multiple lesions, 9.5-10.5 mCi of (18)F-FDG were injected 3-5 hours before radioguided surgery using a PET-dedicated probe (Gamma locator DXI-GF&E). RESULTS: ROLL technique: All lesions injected with nanocolloid were resected (6 lesions in 5 patients, 1 patient with 2 lesions), and recurrence was histologically confirmed. PET probe: Fourteen out of 16 hypermetabolic lesions detected on the PET-CT were resected. One cervical and one mediastinal lymph node in different patients could not be excised. Histological recurrence was confirmed in 12 out of 14 lesions. In one patient, the 2 lymph nodes excised were inflammatory. CONCLUSIONS: (18)F-FDG PET-CT can be key in deciding surgical approach and appropriate radioguided protocol. When lesions are solitary and easily accessible, ROLL technique seems the method of choice. PET probe is more adequate for less accessible lesions.

[Incidence of focal myocardial (18)F-FDG uptake and correlation with coronary calcifications by PET/CT]. / Incidencia de focos miocárdicos de captación de (18)F-FDG y su relación con la presencia de calcificaciones coronarias por PET/TC.

OBJECTIVE: To evaluate the incidence of (18)F-FDG focal uptake in the myocardium as well as its correlation with coronary vessel calcifications. MATERIAL AND METHODS: A total of 130 patients who underwent an oncological PET/CT study were reviewed retrospectively. Sixty-five had undergone a myocardial perfusion study because of clinical suspicion of coronary artery disease (group 1). There were no significant differences in age and gender regarding another group of the same series (n=65; group 2). Focal myocardial (18)F-FDG uptake and the presence of coronary vessel calcifications were identified by 2 independent observers. RESULTS: Group 1: in 18 out of 65 patients (28%) focal myocardial (18)F-FDG uptake was identified (5 had 2 foci; total: 23 foci). In 43 out of 65 studies (66%), calcification was identified in the coronary vessels. Group 2: in 6 out of 65 patients (9%) focal myocardial (18)F-FDG uptake was identified (1 had 2 foci; total: 7 foci). In 17 out of 65 studies (26%), calcification was identified in the coronary vessels. Comparative analysis: focal myocardial (18)F-FDG uptake and coronary vessel calcifications were more frequent in the group 1 patients (p<0.01). There was no correlation between the presence of coronary vessel calcifications and focal myocardial (18)F-FDG uptake in individual patients in both groups (group 1: p=0.7; group 2: p=0.163). CONCLUSIONS: PET/CT allows simultaneous assessment of focal myocardial (18)F-FDG uptake and myocardial vessel calcifications. Patients with clinical suspicion of coronary artery disease have a higher incidence of focal myocardial (18)F-FDG uptake and coronary calcifications. However, (18)F-FDG focal uptake is often observed in sites remote from those with calcification.

Value of FDG-PET for monitoring treatment response in patients with advanced GIST refractory to high-dose imatinib. A multicenter GEIS study.

AIM: The aim of this study was to evaluate the utility of positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) in monitoring response in refractory GIST. METHODS: This multicenter study prospectively evaluated 21 patients with locally advanced and/or metastatic GIST refractory to with high-dose imatinib (800 mg/day) treated with doxorubicin 15-20 mg/m2/weekly for 4 cycles, followed by imatinib maintenance (400 mg/day). CT and FDG-PET were performed at baseline and after completion of therapy. RESULTS: Mean baseline tumor size on CT was 5.9 cm. Median progression-free survival (PFS) was 219 days (range 62-1108). Three out of 21 patients (14%) had partial responses (PR) under RECIST criteria, 12 patients (57%) remained stable (SD) and 6 showed progression (PD) of the disease during treatment (29%). Six patients had PR by FDG-PET, 15 showed SD (n=9) or PD (n=6) based on EORTC criteria. Patients with a PFS <6 mo showed a significantly higher ∑SUVmax at baseline (26.04±13.4) than those with PFS≥6 mo (9.82±5.0) (P<0.05). A correlation was found between PET response and PFS: PR 14±6.1 mo, SD 5.5±0.8 mo and PD 3.5±4.1 mo (P<0.05). A residual SUVmax <5 after treatment correlated with improved PFS (314±315 days vs 131±91 days) (P<0.01). Survival curves showed a significant association between PET response and PFS (P<0.05). Patients with wild-type genotype KIT (KIT-WT) showed a significantly lower baseline SUVmax (5.36±1.4) than non-WT KIT (8.40±3.6) (P<0.05). CONCLUSION: FDG-PET is useful in assessing response of GIST refractory to imatinib and correlates with the presence of KIT-WT. Baseline ∑SUVmax can predict response to treatment in this series.