Time Of PET Scan Research Articles

Is there a role for 11C-choline PET/CT in the early detection of metastatic disease in surgically treated prostate cancer patients with a mild PSA increase <1.5 ng/ml?

The aim of this study was to evaluate the potential usefulness of whole-body (11)C-choline PET/CT in the re-staging of prostate cancer (PC) patients previously treated with radical prostatectomy (RP), who presented a mild increase of prostate-specific antigen (PSA) <1.5 ng/ml (early biochemical relapse) during follow-up (FU). We evaluated 102 consecutive patients (mean age = 68 years, range = 54-82 years) previously treated with RP and who presented during FU a mild increase of trigger PSA serum levels <1.5 ng/ml: mean 0.86 ± 0.40 ng/ml (range 0.2-1.5) and median 0.93 ng/ml (range 0.67-1.10). In this patient series (11)C-choline PET/CT was used as the first imaging examination at the time of the detection of a mild serum PSA increase <1.5 ng/ml. (11)C-Choline PET/CT was performed following standard procedures in our centre. At the time of PET/CT, 86 patients were not receiving any pharmacologic treatment, while 16 were under anti-androgenic therapy. Positive PET findings were validated by: (a) transrectal ultrasound (TRUS)-guided biopsy in cases of local recurrence, (b) surgical lymphadenectomy, (c) other imaging procedures or (d) FU lasting for at least 12 months. Univariate and multivariate analyses were used to evaluate the following variables: age, TNM staging, Gleason score, time from RP to the biochemical relapse, anti-androgen therapy at the time of (11)C-choline PET/CT scan, trigger PSA value and PSA kinetics, i.e. PSA doubling time (PSAdt) and PSA velocity (PSAvel), in order to assess the significant predictive factors related to the findings of a positive (11)C-choline PET/CT scan. Overall, (11)C-choline PET/CT showed positive findings in 29 of 102 patients (28% of cases). In detail, (11)C-choline PET/CT detected: local relapse in 7 patients, bone metastases in 13 patients (4 single and 9 multiple) and lymph node metastases in 9 patients (6 single and 3 multiple). Positive PET findings were validated by: (a) TRUS-guided biopsy in 7 patients with local recurrence, (b) surgery and lymphadenectomy in 3 patients, (c) other targeted imaging procedures (MR or bone scan) in 5 patients and (d) clinical FU lasting a minimum of 12 months and including also a contrast-enhanced CT (CECT), an MR, a bone scan and a repeated (11)C-choline PET/CT in 14 patients. Age, time to biochemical relapse (TTR), initial T staging, Gleason score and trigger PSA were not statistically significant in predicting a positive (11)C-choline PET/CT scan both at univariate and multivariate analysis. Instead, PSA kinetics (PSAdt and PSAvel), N status and anti-androgenic therapy at the time of PET scan were statistically significant predictive factors at univariate analysis. Of note, only PSAdt and initial N status were found to be significant and independent predictive factors at multivariate analysis. The mean PSAdt in PET-positive patients was 4.34 months (SD 2.82) while in PET-negative patients it was 13.30 months (SD 9.75) (p = 0.0001). The optimal threshold for PSAdt established by receiver-operating characteristic (ROC) analysis was 7.25 months (AUC 0.85; 95% confidence interval 0.77-0.91) providing 93% sensitivity, 74% specificity, 60% positive predictive value and 96% negative predictive value. In our study, (11)C-choline PET/CT was able to detect recurrent disease in 28% of the patients with mild biochemical relapse characterized by very low trigger PSA levels (PSA <1.5 ng/ml). Very interestingly (11)C-choline PET/CT detected distant unexpected metastases in 21% of the patients. At multivariate statistical analysis only PSAdt and node status were shown to be significant and independent predictive factors for positive (11)C-choline PET/CT. Therefore, (11)C-choline could be suggested to be performed early during initial biochemical relapse in patients presenting with fast PSA kinetics. The early detection of the site of recurrence could lead to a prompt instauration of the most appropriate treatment, i.e. local surgery or radiation treatment vs systemic treatment. In this view, one of the main advantages should be the avoidance of unnecessary local radiotherapy in those patients showing distant metastasis at (11)C-choline PET/CT.

Serum TARC Levels Correspond with Tumor Load and Response to Chemotherapy in Classical Hodgkin Lymphoma Patients.

Abstract 3663Poster Board III-599 IntroductionThymus and Activation Related Chemokine (TARC) is produced in high amounts by Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL). It attracts CCR4 positive Th2 and Treg cells, which are typically present in large numbers in the reactive infiltrate in cHL. TARC can be measured in the serum of cHL patients and is usually elevated in the presence of active disease, as compared to healthy controls. Higher levels are observed in advanced stage disease, compared to stage I disease. The goal of the current study was to correlate TARC serum levels to metabolic response to therapy as measured by FDG-PET scanning. Patients and methodsNewly diagnosed cHL patients treated in our hospital were asked to participate. Serum samples were taken before the start of treatment, at the time of the mid treatment PET scan (after 2 cycles of ABVD for stage I and II, or mid BEACOPP or ABVD treatment for stage III and IV disease) and at the time of the PET scan after completion of chemotherapy. TARC serum levels were measured by ELISA and TARC immunohistochemistry was done on primary involved lymph node tissue. ResultsA total of 59 cHL patients, median age 40 (range 16-80) and 49% male participated. Eight patients had stage I, 26 stage II, 14 stage III and 10 stage IV disease. The known association of high pretreatment TARC levels with advanced stage was also significantly present in our data, supporting the hypothesis that serum TARC levels reflect tumor burden. Moreover, in stage I and II patients, bulky disease (27%) was associated with a significant higher TARC level, lending further support to this hypothesis. Compared to pretreatment values, TARC levels had decreased significantly at mid treatment and treatment completion to the range of healthy controls. Only in stage I there was no significant difference between pretreatment and mid or after treatment samples (see figure), probably due to the relatively large number of patients without elevated TARC before the start of therapy. In patients with a positive PET scan at mid treatment (26%), there was a trend for a higher TARC level (P=0.08) compared to PET negative patients. After completion of chemotherapy PET positivity (19%) was significantly associated with a higher TARC level. Three patients had a relapse and at that time TARC levels had clearly increased in comparison to the levels after treatment. Conclusionsserum TARC levels are associated with tumor burden and metabolic response to therapy as measured by FDG-PET scan. Measurement of serum TARC levels is a potential tool to evaluate the response to therapy and to be used in follow up after completion of chemotherapy. Inclusion of more patients is necessary to further assess the clinical value of TARC serum levels and is ongoing. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Computer-assisted quantification of lung tumors in respiratory gated PET/CT images: phantom study

A computer-aided method was developed to automatically localize tumors in lung PET images of discrete bins within the breathing cycle, followed by an algorithm that registers all the information of a complete respiratory cycle into a single reference bin. Four registration/integration algorithms: Centroid Based, Intensity Based, Rigid Body, and Optical Flow registration were compared as well as two registration schemes: Direct scheme and Successive scheme. Validation was demonstrated by conducting experiments with the computerized 4D NCAT phantom and with a dynamic lung-chest phantom imaged using a GE PET/CT System. Iterations were conducted on different size simulated tumors. Static tumors without respiratory motion were used as gold standard; quantitative results were compared with respect to tumor activity concentration, cross-correlation coefficient, relative noise level, and computation time. After motion correction, the best compromise between short PET scan time and reduced image noise can be achieved, while quantification and clinical analysis become faster and more precise.

FDG-PET Guided Consolidative Radiotherapy in Patients with Advanced Stage Hodgkin Lymphoma with Residual Abnormalities on Post Chemotherapy CT Scan.

Consolidative radiotherapy (RT) is often administered following chemotherapy for advanced stage Hodgkin lymphoma (HL) with bulky disease at diagnosis or for residual abnormalities on post-chemotherapy CT imaging. It is unknown whether RT is necessary for such patients if the residual mass is FDG-PET-negative (PET-neg) following chemotherapy (CHT). Further, it has been previously shown that a post-therapy PET-positive (PET-pos) scan is highly predictive of future relapse; however, it is unclear whether consolidative RT can be used to salvage these cases.Methods Since July 2005, adult (> 16 y) patients in British Columbia (BC) with advanced stage HL (stage III /IV and/or the presence B symptoms and/or bulky disease (> 10cm)) have been treated with 6 cycles with ABVD followed by a PET scan for further treatment planning if residual abnormalities ≥2 cm were observed on CT imaging. Prior to this, post-treatment PET scans were obtained in some individuals by self-pay. If the PET scan was positive, RT was administered if feasible, otherwise, patients were observed. There were 68 eligible patients, including 7 self-pay patients, that were identified in the BC Lymphoid Cancer Database. 16 patients were excluded (PET not performed (5); palliative tx or refusal (3); composite lymphoma (1); progressive disease during CHT or at the time of PET scan (4); HIV + (1); PET mid-therapy (1); death due to unrelated cause prior to PET scan (n=1).), leaving a total of 52 patients who had a PET scan post-chemotherapy for a residual mass and who had adequate follow-up (median 19 m, 10–59 m). Patient characteristics include: M:F 1.1:1, Median age 29 (17–81); 55% stage II, 46% stage III/IV 44%; 49% bulky disease; 69% B symptoms; IPFP Prognostic score 0 8%; 1 39%; 2 26%; >3 26%.Results In total, 40/52 (77%) were PET-neg and 12/52 (23%) were PET-pos (SUV mean 4.4, 2.2–6.8). PET-pos patients had an inferior 2 y PFS compared to PET-neg patients (26% vs 91%, p=.001). In the PET-pos group, 10/12 received the planned RT and 5 have relapsed. In the PET-neg group, there was no difference in the 2 y PFS in patients with bulky (n=17) vs non-bulky disease (n=20) (86% vs 94%, p=.35).Conclusions Advanced stage HL patients who achieve a post-CHT PET-neg status are at a low risk of relapse and do not require additional consolidative RT thus avoiding potential long-term side effects. The majority of patients with bulky disease who have a PET-neg scan following CHT also remain in remission, however, longer follow-up is still needed. Although some patients with a positive PET-scan may be salvaged by consolidative RT, a high proportion ultimately relapse. [Display omitted] [Display omitted]

Correlation of 11C-choline PET and PSA values in patients with prostate cancer and biochemical relapse after primary treatments

5073 Background: 11C-choline PET has demonstrated promising results in the evaluation of suspected recurrence after a primary treatment in prostate cancer (PC) patients (pts). However in pts with asymptomatic biochemical relapse (BR), the timing of PET scan is a subject of controversy. Most authors argue against performing PET scan for rising PSA values &lt;5 ng/ml. Aim of our study was to evaluate if there is a PSA cut-off that significatively correlates to 11C-choline PET positivity. Methods: 68 pts with rising PSA after primary treatment underwent 11C-choline PET. Median age was 68 yrs (range 43–84). Median PSA at the time of PET scan was 2.91 ng/ml (range 0.12- 71.60). Primary treatments were: 27 (40%) radical prostatectomy (RP), 22 (32%) external-beam radiation therapy (EBRT), 13 (19%) RP + adjuvant EBRT, 6 (9%) hormonal therapy. Results: 11C-choline PET was positive in 39/68 pts (57%) and negative in 29/68 (43%). Median PSA values were 1.18 ng/ml (range 0.12–6.47) and 5.14 ng/ml (range 1.33–71.60) in pts with negative and positive PET scan respectively. Median PSA values were statistically different in positive and negative 11C-choline PET (Mann-Whitney U Test. p&lt; 0.001). No positive uptake was seen in pts with PSA &lt;1 ng/ml (12/68); all pts with PSA &gt;6.5 ng/ml had a positive finding; for PSA values between 1 and 6.5 ng/ml (33/68), 11C- choline PET showed a pathological uptake in 18 pts. The Receiver Operative Characteristic (ROC) analysis found that a PSA cut-off of 2.31 ng/ml has a sensitivity of 87% and a specificity of 83% in respect of 11C-choline PET positivity. Conclusions: For PSA values &gt; 2.3 ng/ml the probability to have a positive 11C-choline PET is high in order to recommend to perform the exam in clinical practice, even if further data are needed. On the contrary, we can’t suggest to perform PET scan in pts with PSA &lt;1 ng/ml. No significant financial relationships to disclose.

Relationship between survival and PET measurements of tumour blood flow, in patients with metastatic colorectal cancer

20021 Background: There are conflicting reports on the relationship between tumour blood flow and patient survival. Poor flow is associated with tumour hypoxia and has been associated with a poor outcome (Lehtio et al 2004;Int J Radiat Oncol Biol Phys:59, 971–982). However, good flow is associated with angiogenesis which drives tumorigenesis, and has also been linked with a poor prognosis (Hermans 200 Int J Radiat Oncol Biol Phys:57, 1351–6). In this study, we examined the relationship between PET measurements of blood flow in liver metastases, and survival, in patients with colorectal cancer. Methods: Thirty seven patients with metastatic colorectal cancer, with a range of previous treatments, were studied. Regional perfusion was measured in liver metastases using H2[15O] or C[15O]2 PET. Blood flow was correlated with overall survival from the time of PET scan. Relationship between outcome and flow was analysed separately for patients with 1 or &gt;1 metastatic sites; a recent meta-analysis of patient with metastatic colorectal cancer showed number of metastatic sites to be an independent prognostic factor (Kohne et al 2002; Ann Oncol. 13, 308–317). Results: There was no significant relationship between survival and metastasis blood flow when the data were taken as a whole. However, when the data were corrected for number of metastatic sites, there was a trend for high flow to be associated with shorter survival (p = 0.063). Specifically, for patients with multiple metastatic sites, median survival times for patients with high flow (n = 9) was 171 days [95% CI 25–317] compared with 441 days [95% CI 12–870] for patients with low flow (n = 7) (p = 0.026). Conclusions: In patients with multiple sites of metastasis, high tumour blood flow is a poor prognostic factor. This may be due to angiogenesis, which promotes tumorigenesis. No significant financial relationships to disclose.

FDG-PET in immunocompetent patients with primary central nervous system lymphoma: correlation with MRI and clinical follow-up

The role of FDG-PET in primary central nervous system lymphoma (PCNSL) is unclear. It was the aim of this study to investigate the role of FDG-PET in detecting PCNSL and in predicting response to chemotherapy. An FDG-PET scan of the brain was performed in 15 patients with histologically proven PCNSL (16 PET examinations, Siemens ECAT EXACT). PET was planned to investigate patients at the time of primary diagnosis, after chemotherapy and at the time of suspected relapse in seven, five and three cases, respectively. All except two patients simultaneously underwent MRI of the brain. FDG-PET results were correlated with histological results after stereotactic biopsy (primary diagnosis group) and with clinical data and MRI during follow-up. Six of the seven patients in the primary diagnosis group demonstrated a true positive finding (86%). In one of the true positive PET patients, there were two tumour lesions, one of which was only detectable on the FLAIR MRI sequence. In five patients, FDG-PET showed no sign of PCNSL during ongoing chemotherapy. These results were confirmed by the clinical follow-up (mean 26.6 months). MRI demonstrated minimal residual disease which had disappeared on further follow-up MRI in three of these five patients at the time of PET scanning. Recurrence of disease was confirmed concordantly by FDG-PET and MRI in three different patients. The standardised uptake value of all tumours was 10.2 (4.3-13.7). PCNSLs demonstrate high FDG uptake and can be diagnosed by FDG-PET with high sensitivity. It seems that FDG-PET is suitable for early therapeutic monitoring after chemotherapy.

How to optimize staging in early non-small cell lung cancer

The topic was discussed by Dr Johan Vansteenkiste, Leuven Belgium. PET is an exciting new imaging modality that has rapidly acquired a prominent position in evaluation of solitary pulmonary nodules (SPN) and staging of lung cancer. It is based on the principle that cancer cells have a higher rate of glycolysis and an increased cellular uptake of glucose due to increased number of transport proteins than non-neoplastic cells. The PET tracer, 18 fluoro-deoxyglucose (18 FDG) is taken up into cells and metabolically trapped and accumulates. 18 FDG is a positron emitter, and therefore, can be measured. Thus, PET provides evidence of metabolic activity of tumor cells and has opened up the relative new field of ‘molecular imaging’. PET has a sensitivity of approximately 90% and a specificity of 85 /90% for evaluating SPN, but the data available is based on nodules ]/1 cm in size [1]. The resolution limit of PET is thought to be 7 /8 mm. For nodules smaller than 1 cm, the sensitivity and specificity is unknown. The sensitivity and specificity of the CT scan for evaluating mediastinal lymph nodes for metastasis is 60 /70% each [2,3]. This means that 30 /40% of lymph nodes one cm or smaller will have microscopic metastasis (sensitivity) and 30 /40% of lymph nodes /1 cm in size will not contain metastases, but will only be reactive (specificity). In contrast, data presented and a published meta-analysis documents a sensitivity of 89% and specificity of 92% for PET evaluation of mediastinal nodes in patients with NSCLC [4]. A limitation of PET is that it lacks precise anatomic details. Studies have shown that the sensitivity and accuracy of PET is significantly improved when it is correlated with the CT scan. New scanners are just coming on the market that fuse the CT and PET images, thus giving better anatomic detail. It is likely that these new CT/PET scanners may replace the current PET scanners. They decrease the PET scan time from 60 to 30 min. False positive PET scans can occur in patients with tuberculosis, other granulomatous disease, sarcoidosis, and anthrasilicosis. Care must be taken to distinguish a malignancy adjacent to mediastinum from adjacent mediastinal nodal metastasis with the current scanners. False negative PET scans may occur in patients with carcinoid tumors and bronchoalveolar cell carcinoma because of the low metabolic activity. PET will also miss microscopic lymph node metastases (resolution size limitation). Dr Vansteenkiste recommended that PET evaluation of mediastinum be used as follows:

Muscarinic cholinergic receptors in human narcolepsy: a PET study.

To investigate the function of the muscarinic cholinergic receptor (mAchR) in narcolepsy and the effects of pharmacotherapy on mAchRs. Muscarinic neural transmission serves as the main executive system in REM sleep. Studies in canine narcolepsy reported an increase in mAchRs in the pons. The mAchRs of 11 drug naive/free patients with narcolepsy and 21 normal controls were investigated using PET with [11C]N-methyl-4-piperidylbenzilate ([11C]NMPB). Measurements were done in the pons, thalamus, striatum, and cerebral cortex. Seven of the 11 patients also underwent additional PET scans after the alleviation of symptoms by pharmacotherapy. There were no differences in [11C]NMPB binding between the control and drug naive/free patients in all areas analyzed. At the time of on-medication PET scan, [11C]NMPB binding in the thalamus was decreased, but only to a small degree compared with that by anticholinergic drugs. The present results do not support the notion that the mAchR is the main site of action of pharmacotherapy in the marked clinical improvement of human cataplexy.

Tactile exploration of shape after subcortical ischaemic infarction studied with PET.

We studied the cerebral activations related to restitution of hand function in five patients with first hemiplegic subcortical stroke due to ischaemic infarction in the area of the basal ganglia or thalamus. In two subjects, involvement of the cortico-spinal tract was demonstrated by magnetic evoked potentials. The subjects were requested to discriminate rectangular parallelepipeda of identical mass with their affected hands. Regional cerebral blood flow (rCBF) was measured with PET after intravenous bolus injection of [15O]butanol, at rest and during task execution. Evaluation of the rCBF changes was based on pixel-by-pixel t statistics of spatially standardized and averaged PET images and on a statistical distribution analysis of regions of interest in the individual subjects. For anatomical localization of the significant rCBF changes, a computerized brain atlas (Greitz et al. J Comput Assist Tomogr 1991; 15: 26-38) and a matching procedure that directly aligns individual PET and high resolution magnetic resonance images were used. The rCBF at rest and the task-induced rCBF changes varied from subject to subject, as did the residual neurological deficits at the time of PET scanning. In all subjects there were large activation areas in the motor and the sensory hand area contralateral to the affected hand. Poor performance of the task was correlated with a low rCBF in the contralateral sensorimotor cortex at rest and a bilateral activation of the primary sensorimotor cortex during task performance. The premotor cortex, ipsilateral and anterior cerebellum, contralateral to the affected hand, were also significantly activated. Further activations were observed in the contralateral premotor cortex, supplementary motor area and bilaterally in the posterior cingulate cortex, but were less consistent among the subjects. Our data suggest that recovery from hemiplegic stroke is associated with a marked reorganization of the cerebral activation patterns, including common and subject-specific activation sites. With respect to task-specific information processing a lower discrimination rate of objects compared with controls was associated with diminished activations in parietal lobe.

Local cerebral glucose abnormalities in mild closed head injured patients with cognitive impairments.

Mild-moderate closed head injury (CHI) can be followed by neuropsychological impairments in recent memory and attention, despite the absence of discernible structural abnormalities in a significant number of patients. To determine whether CHI may result in cerebral glucose metabolic abnormalities, we used fluorodeoxyglucose (FDG) technique with PET imaging to measure local cerebral metabolic rates for glucose (LCMRGlu) in three CHI patients and three matched normal controls. The CHI patients were between 3-12 months post-injury. All had deficits in attention and recent memory shown by neuropsychological testing. CT, MRI, EEG and drug screens were negative at the time of PET scanning. Subjects were engaged in a vigilance task throughout the initial 30 min following FDG administration. Group comparisons were made using t tests. There were no significant group differences found in global glucose metabolic rate. Nevertheless, the CHI group exhibited significantly decreased LCMRGLu in medial temporal, posterior temporal, and posterior frontal cortices, as well as in the left caudate nucleus. LCMRGlu was significantly increased, relative to controls, in anterior temporal and anterior frontal cortices. These results suggest that CHI patients can have regional glucose metabolic abnormalities, indicative of altered neuronal function, despite the absence of discernible anatomic abnormalities.