Current progress and future perspectives in total‐body PET imaging, part I: Data processing and analysis

Small-animal positron emission tomography as a tool for neuropharmacology

What Is the Role of Positron Emission Tomography in Osteonecrosis of the Jaws?

The Case Against Heavy PETing

Accurate identification of eloquent cortex is important to ensure that resective surgery in the region surrounding the central sulcus is performed with minimum risk of permanent neurological deficit. Functional localization has traditionally been accomplished using intraoperative cortical stimulation (ICS). However, this technique suffers from several disadvantages that make the development and validation of noninvasive methods desirable. Functional localization accomplished by activation studies in which positron emission tomography (PET) scanning and the tracer [15O]H2O have been used has been shown to correlate well with the results of ICS. Another noninvasive method for functional localization is functional magnetic resonance (fMR) imaging. We compared the locations of activation peaks obtained in individual patients using fMR and [15O]H2O PET imaging. Twenty-six combined PET activation-fMR imaging studies were performed in 11 patients who were admitted for evaluation before undergoing surgery in the region surrounding the central sulcus. The PET scans were obtained using bolus injections of the cerebral blood flow tracer [15O]H2O (10 mCi). Multislice T2*-weighted gradient-echo echoplanar images were acquired using a 1.5-tesla MR imaging system. Activation maps were aligned with anatomical MR images and transformed into stereotactic space, after which the locations of activation peaks obtained using both modalities were compared. The average distance between activation peaks obtained using fMR imaging and those obtained using PET imaging was 7.9+/-4.8 mm (p>0.05), with 96% of the peaks being located on either the same or adjacent sulci and gyri. Overlapping of voxels activated by each modality occurred in 92% of the studies. Functional MR imaging failed to activate the primary sensorimotor cortex in one study and produced results that were ambiguous in the clinical setting in three cases. Overall, fMR imaging produced activation that correlated well with that obtained using PET scanning. Discrepancies between the sites of activation identified using these two techniques may reflect differences in their physiological bases.

17113 Background: MPM is a rapidly progressive malignancy with a median survival of 6 to 9 months. Studies in non-small cell lung cancer, gastrointestinal stromal tumours, and breast cancer suggest that Positron Emission Tomography (PET) scanning may predict the clinical outcome of chemotherapy at an early stage of treatment. The role of PET in predicting and monitoring response to treatment in MPM is unclear. In this study we assessed if baseline and early interval PET scanning could be of benefit in MPM, correlating the results with standard Computerised Tomography (CT) assessment using the modified Response Evaluation Criteria In Solid Tumours (RECIST) of Byrne and Nowak. Methods: 10 patients with histologically proven MPM proceeded to baseline PET and CT scanning prior to chemotherapy. In 8 patients a second PET scan was performed within three weeks of commencing treatment. The following PET derived parameters were calculated: Standard Uptake Value (SUV)maximum, SUVaverage, PETvolume, and Total Lesion Glycolysis (TLG). Baseline SUVmaximum and early PET response was compared with CT response and survival. Results: Baseline SUVmaximum predicted subsequent CT response in the 10 patients studied. Four out of 5 patients with baseline SUVmaximum of <15 showed a subsequent partial response on CT, whilst the 5th patient had resolution of a pleural effusion. All 5 patients with baseline SUVmaximum of >15 had stable or progressive disease on CT. In contrast change in early SUVmaximum from baseline to 3 weeks did not predict subsequent CT response (Kappa value 0.07) in the 8 patients evaluated. Change in PET volume and TLG correlated with subsequent CT response (Kappa value= 0.80 for both). Only 1 patient with a partial response on % PETvolume and %TLG has died 14 months after commencing treatment. The other 3 patients are alive at 17+, 19+ and 20+ months. The 4 patients with stable or progressive disease using these parameters were deceased at 5, 6, 10, and 12 months respectively. Conclusion: PET may be useful in predicting and evaluating response to treatment in MPM. Furthermore, the results suggest that PET response may be a useful prognostic tool in this disease. It is important to use the appropriate PET derived parameters. Further study with a larger patient population is warranted. No significant financial relationships to disclose.

Background and Purpose: Glioblastomas are the most aggressive of all gliomas. The prognosis of these gliomas, which are classified as grade IV tumors by the World Health Organization (WHO), is poor. Combination therapy, including surgery, radiotherapy, and chemotherapy has variable outcomes and is expensive. In light of rising healthcare costs, there are societal demands for the justification of medical expenses. Therefore, we calculated the cost-effectiveness of follow-up [18F] fluoroethyl-L-tyrosine ([18F] FET) positron emission tomography (PET) scans performed on patients with glioblastoma after surgery and before commencing temozolomide maintenance treatment.Materials and Methods: To determine the cost-effectiveness of follow-up [18F] FET PET procedures, we examined published clinical data and calculated the associated costs in the context of Belgian healthcare. We subsequently performed one-way deterministic sensitivity analysis and Monte Carlo analysis on the calculated ratios.Results: The decision tree based on overall survival rates showed that the number of non-responders identified using PET was 57.14% higher than the number of non-responders identified using conventional MRI. Further, the decision tree based on progression-free survival rates revealed a comparable increase of 57.50% non-responders identified. The calculated cost of two required PET scans per patient during the follow-up treatment phase was 780.50 euros. Two cost-effectiveness ratios were determined for overall survival and progression-free survival rates. Both of these calculations yielded very similar results: incremental cost-effectiveness ratios of 1,365.86 and 1,357.38 euros, respectively, for each identified non-responder. The findings of the sensitivity analysis supported the calculated results, confirming that the obtained data were robust.Conclusion: Our comparative study of conventional MRI and [18F] FET PET revealed that the latter is a valuable tool for predicting the treatment responses of patients with glioblastomas to follow-up temozolomide maintenance treatment while considering its cost-effectiveness. Thus, [18F] FET PET scans enable clinical outcomes to be predicted accurately and at a low cost. Moreover, given the robustness of the data in the sensitivity analyses, the level of certainty of this outcome is acceptable.

ABSTRACTObjective: Physiologic uptake of 18F-fluorodeoxyglucose (FDG) in brown adipose tissue (adipose tissue) of cancer patients may confound interpretation of positron emission tomography (PET) scans. Uptake in adipose tissue occurs in up to half of pediatric oncology patients undergoing PET scans, and is especially common in adolescents. adipose tissue is innervated by the sympathetic nervous system, and beta blockers such as propranolol have shown efficacy in reducing adipose tissue uptake on PET scans done in older adult oncology patients. Participants: Because propranolol may cause hypoglycemia or other side effects in fasting patients, we prospectively assessed the safety of a single dose of 20 mg propranolol in adolescent and young adult oncology patients undergoing FDG-PET imaging. Methods: Ten patients (median age 18 years, range 14–24) received propranolol premedication prior to FDG-PET. Results: No adverse effects or clinically significant changes in serum glucose, heart rate, or blood pressure were observed. Five of the 10 patients had adipose tissue identified on previous PET scans. However, following propranolol administration only, one patient had persistent uptake in adipose tissue. Conclusions: Propranolol was convenient and safe in fasting adolescent and young adult oncology patients undergoing PET scans. Larger studies are warranted to better define the effectiveness of this approach.

End-of-treatment but not interim PET scan predicts outcome in nonbulky limited-stage Hodgkin’s lymphoma

A wide array of positron emission tomography (PET) ligands have been developed that provide information relevant to multiple aspects of addiction (1-3).Locations of targets are approximated on this diagram, which is color-coded by functional roles.On the presynaptic side (pink), targets include neurotransmitter precursors (orange, example [ 18 F]-fluorodopa, FDOPA), modulatory receptors (yellow, examples [ 11 C] GR103545, [ 11 C] LY27950509 and [ 18 F] LY2459989 for kappa opioid receptors, KOR; [ 18 F]FMPEP for cannabinoid 1 receptors, CB1), and neurotransmitter reuptake transporters (light green, examples [ 11 C] PE2I and [ 18 F] FE-PE2I for the dopamine transporter, DAT).On the postsynaptic side (purple), targets include neurotransmitter receptors (blue, examples [ 11 C] raclopride and [ 11 C]-(1)-PHNO for dopamine D 2 and D 3 receptors, D 2 R; [ 11 C] carfentanil for mu opioid receptors, MOR; [ 18 F] LY2459989 for both mu and kappa opioid receptors; 2-[ 18 F]fluoro-3-(2(S)-azetidinylmethoxy) pyridine for nicotinic acetylcholine receptors, nAChR).Some PET ligands target more generic functions.[ 18 F]-fluoro-deoxy-glucose (FDG) PET provides a measure of cerebral metabolic rate.

9028 Background: AP23573 (AP) is a non-prodrug rapamycin analog, which potently inhibits mTOR, a downstream effector of the PI3K/Akt pathway. AP has demonstrated some anti-tumor efficacy in sarcoma in phase I study. The relationship between mTOR and the glycolytic pathway provides mechanistic rationale for the use of PET as a non-invasive indicator of mTOR activity. Early response evaluation by PET was studied in this phase 2 trial in advanced sarcoma pts. Methods: AP is dosed at 12.5 mg IV daily X 5 days every 2 weeks (1 course). PET scan was done on D1 and D5 of the first course of AP using a CTI Viewer 16 PET/CT scanner with LSO crystals (11 pts) or a Siemens Biograph 2 PET/CT scanner with LSO crystals (14 pts). The five areas with highest FDG accumulation at baseline were selected as target lesions. Percent difference in sum of maximum standard uptake values (SUVmax) were compared for each patient on D1 and D5. These values represent a measure of FDG uptake. Response criteria used were recommended by the EORTC PET Study Group (Eur J Cancer. 1999; 35; 1773–1782). In the targeted lesions D5, SUVmax normalization was considered as complete metabolic response (CMR), while >25% SUVmax reduction was considered partial metabolic response (PMR). Stable metabolic response (SMR) was defined by an SUVmax change less then ±25% and increased metabolic response (IMR) was considered >25% increase in SUVmax. Further evaluation with PET scan is planned after 4 courses of AP. Results: 25 pts (14M/11F) were enrolled (age 18–76 yrs, median 57 yrs). Two pts showed no abnormal 18-FDG accumulation on D1, hence D5 PET was omitted. Of the remaining 23 pts, 9 pts (39%) showed PMR (SUV decreased by 25.3–58.7%). 14 pts (61%) had SMR (9 pts had SUV decrease by 4.7–21.6% and 5 pts had SUV increase by 0.7–5.5%). None of the patients had IMR or CMR. 5/9 pts with PET evidence of PMR showed clinical improvement as demonstrated by reduced symptoms of pain, shortness of breath and cough. Conclusions: This is the first known report of the use of PET to evaluate mTOR inhibition in non-GIST sarcomas. PET appears to be valuable in initial evaluation of patient response to treatment with AP. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ariad Ariad Ariad

In the management of brainstem lesions, the place of stereotactic biopsy sampling remains debatable. The authors compared the results of magnetic resonance (MR) imaging, positron emission tomography (PET) scanning, and histological studies obtained in 30 patients who underwent MR imaging- and PET-guided stereotactic biopsy procedures for a brainstem mass lesion. Between July 1991 and December 1998, 30 patients harboring brainstem mass lesions underwent a stereotactic procedure in which combined MR imaging and PET scanning guidance were used. Positron emission tomography scanning was performed using [18F]fluorodeoxyglucose in 16 patients, methionine in two patients, and both tracers in 12 patients. Definite diagnosis was established on histological examination of the biopsy samples. Interpretation of MR imaging findings only or PET findings only was in agreement with the histological diagnosis in 63% and 73% of cases, respectively. Magnetic resonance imaging and PET findings were concordant in 19 of the 30 cases; in those cases, imaging data correlated with histological findings in 79%. Treatment based on information derived from MR imaging was concordant with therapy based on histological findings in only 17 patients (57%). Combining MR imaging and PET scanning data, the concordance between the neuroimaging-based treatment and treatments based on histological findings increased to 19 patients (63%). In seven patients who underwent biopsy procedures with one PET-defined and one MR imaging-defined trajectory, at histological examination the PET-guided samples were more representative of the tumor's nature and grade than the MR imaging-guided samples in four cases (57%). In 18 patients PET scanning was used to define a biopsy target and provided a diagnostic yield in 100% of the cases. Although the use of combined PET and MR imaging improves radiological interpretation of a mass lesion in the brainstem, it does not accurately replace histological diagnosis that is provided by a stereotactically obtained biopsy sample. Combining information provided by MR imaging and PET scanning in stereotactic conditions improves the accuracy of targeting and the diagnostic yield of the biopsy sample; an MR imaging- and PET-guided stereotactic biopsy procedure is a safe and efficient modality for the management of mass lesions of the brainstem.

612 Background: Breast Conservation Therapy (BCT) for early breast cancer is an effective option in selected patients with primary breast cancer. Mammographic evaluation of breast abnormalities developing after BCT can be difficult. Positron Emission Tomography (PET) is a valuable imaging tool in oncology. We investigated the efficacy of PET imaging in predicting the nature of suspicious breast changes following BCT. Methods: All patients with prior BCT with suspicious mammographic or breast examination findings necessitating biopsy evaluation were offered participation. After signed informed consent, PET imaging was performed using F-18 FDG General Electric PET scanner. Breast biopsy was obtained following the PET scan. Pathologic findings were correlated with the PET findings. Results: 33 patients were enrolled in the study between 6/1997 and 11/2003 with 31 patients completing both PET imaging and breast biopsy. The population characteristics at the time of the original breast cancer diagnosis were as follows: (1) Race and age: African Americans 21 (68%) (mean age = 46.8), Caucasian 10(32%) (mean age = 52.8). (2) Tumor size: 7 tumors ≤ 10mm, 11 between 11–20mm, 11 between 21–30mm, and 2 between 31–50mm. (3) Nodal Status: 21(68%) node negative, 10(32%) node positive. (4) Hormone receptor status: 51% negative, 49% positive.Biopsy/PET Results: 58% of the surgical biopsies were negative while 42% were positive (recurrent disease). 58% of PET scans were negative while 42% were positive. There was 1 false negative PET scans and 1 false positive scan. Overall the sensitivity of PET was 92.31%;while specificity was 94.44%. Positive predictive value of PET was 92.31%. PET scan was highly consistent with biopsy results (Kappa Co-efficient k=0.92). The single patient with a negative biopsy following a positive PET scan was found to have wide spread metastatic disease. The single patient with negative PET, but positive disease by biopsy had DCIS. Conclusions: PET imaging appears to be a reliable radiographic approach for the initial evaluation of suspicious breast lesions developing after BCT. No significant financial relationships to disclose.

612 Background: Breast Conservation Therapy (BCT) for early breast cancer is an effective option in selected patients with primary breast cancer. Mammographic evaluation of breast abnormalities developing after BCT can be difficult. Positron Emission Tomography (PET) is a valuable imaging tool in oncology. We investigated the efficacy of PET imaging in predicting the nature of suspicious breast changes following BCT. Methods: All patients with prior BCT with suspicious mammographic or breast examination findings necessitating biopsy evaluation were offered participation. After signed informed consent, PET imaging was performed using F-18 FDG General Electric PET scanner. Breast biopsy was obtained following the PET scan. Pathologic findings were correlated with the PET findings. Results: 33 patients were enrolled in the study between 6/1997 and 11/2003 with 31 patients completing both PET imaging and breast biopsy. The population characteristics at the time of the original breast cancer diagnosis were as follows: (1) Race and age: African Americans 21 (68%) (mean age = 46.8), Caucasian 10(32%) (mean age = 52.8). (2) Tumor size: 7 tumors ≤ 10mm, 11 between 11–20mm, 11 between 21–30mm, and 2 between 31–50mm. (3) Nodal Status: 21(68%) node negative, 10(32%) node positive. (4) Hormone receptor status: 51% negative, 49% positive.Biopsy/PET Results: 58% of the surgical biopsies were negative while 42% were positive (recurrent disease). 58% of PET scans were negative while 42% were positive. There was 1 false negative PET scans and 1 false positive scan. Overall the sensitivity of PET was 92.31%;while specificity was 94.44%. Positive predictive value of PET was 92.31%. PET scan was highly consistent with biopsy results (Kappa Co-efficient k=0.92). The single patient with a negative biopsy following a positive PET scan was found to have wide spread metastatic disease. The single patient with negative PET, but positive disease by biopsy had DCIS. Conclusions: PET imaging appears to be a reliable radiographic approach for the initial evaluation of suspicious breast lesions developing after BCT. No significant financial relationships to disclose.

Cost-effectiveness analysis of blood-based biomarker testing in the diagnosis of Alzheimer’s disease pathology

Suggestions for topics suitable for these Point/Counterpoint debates should be addressed to Colin G. Orton, Professor Emeritus, Wayne State University, Detroit: ortonc@comcast.net. Persons participating in Point/Counterpoint discussions are selected for their knowledge and communicative skill. Their positions for or against a proposition may or may not reflect their personal opinions or the positions of their employers.