Misty Long

An Assessment of the Impact of Incorporating Time-of-Flight Information into Clinical PET/CT Imaging

The introduction of fast scintillators with good stopping power for 511-keV photons has renewed interest in time-of-flight (TOF) PET. The ability to measure the difference between the arrival times of a pair of photons originating from positron annihilation improves the image signal-to-noise ratio (SNR). The level of improvement depends upon the extent and distribution of the positron activity and the time resolution of the PET scanner. While specific estimates can be made for phantom imaging, the impact of TOF PET is more difficult to quantify in clinical situations. The results presented here quantify the benefit of TOF in a challenging phantom experiment and then assess both qualitatively and quantitatively the impact of incorporating TOF information into the reconstruction of clinical studies. A clear correlation between patient body mass index and gain in SNR was observed in this study involving 100 oncology patient studies, with a gain due to TOF ranging from 1.1 to 1.8, which is consistent with the 590-ps time resolution of the TOF PET scanner. The visual comparison of TOF and non-TOF images performed by two nuclear medicine physicians confirmed the advantages of incorporating TOF into the reconstruction, advantages that include better definition of small lesions and image details, improved uniformity, and noise reduction.

Time Course of Early Response to Chemotherapy in Non–Small Cell Lung Cancer Patients with 18F-FDG PET/CT

PET and 18F-FDG have the potential to follow the early metabolic response to chemotherapy in patients with non–small cell lung cancer and to predict success or failure of the therapy. Methods: We studied 16 patients with non–small cell lung cancer as they followed 2 courses of docetaxel and carboplatin. Each patient was studied weekly for 7 wk, and tissue activity was assessed by the amount of radioactivity retained 90 min after the intravenous injection of 18F-FDG. In a prospective analysis, the linear least-squares method was used to evaluate the time course of metabolic activity in tumor and liver, bone marrow, and unaffected lung tissues; a metabolic response was defined as a response in which the slope of the regression was negative and significantly different from zero. Our hypothesis was that patients who exhibited a tumor metabolic response would survive longer than those who did not. In a retrospective examination of our data, we grouped our patients into those who survived <6 mo and those who survived longer and calculated the difference in the standardized uptake value (SUV) between day 7 and subsequent time points to determine the most appropriate timing of 2 PET studies in predicting response to therapy. Results: Fifteen of 16 patients completed the study. In the prospective study, 8 patients were classified as nonresponders as the slope of the regression of tumor SUV versus time was not different from zero; they all died within 35 wk of the end of their study. Seven patients were classified as responders; 5 survived and 2 died, one at 25 wk and the other at 76 wk. In the retrospective study, a decrease of 0.5 SUV between studies performed at 1 and 3 wk after the initiation of chemotherapy was predictive of those patients who survived >6 mo and in whom chemotherapy was presumably successful. Conclusion: Patients with non–small cell lung cancer who had a positive outcome, as exhibited by prolonged survival, were those who showed a tumor metabolic response assessed using weekly 18F-FDG PET studies. 18F-FDG PET studies performed at 1 and 3 wk after the initiation of chemotherapy allowed prediction of the response to therapy.

Radioimmunodetection of amyloid deposits in patients with AL amyloidosis

Care of patients with AL amyloidosis currently is limited by the lack of objective means to document disease extent, as well as therapeutic options that expedite removal of pathologic deposits. To address these issues, we have initiated a Phase I Exploratory IND study to determine the biodistribution of the fibril-reactive, amyloidolytic murine IgG1 mAb 11-1F4 labeled with I-124. Patients were infused with less than 1 mg (∼ 74 MBq) of GMP-grade antibody and imaged by PET/CT scan 48 and 120 hours later. Among 9 of 18 subjects, there was striking uptake of the reagent in liver, lymph nodes, bone marrow, intestine, or, unexpectedly, spleen (but not kidneys or heart). Generally, positive or negative results correlated with those obtained immunohistochemically using diagnostic tissue biopsy specimens. Based on these findings, we posit that (124)I-mAb m11-1F4 can be used to identify AL candidates for passive immunotherapy using the chimeric form of the antibody.

Does reducing CT artifacts from dental implants influence the PET interpretation in PET/CT studies of oral cancer and head and neck cancer?

In patients with oral head and neck cancer, the presence of metallic dental implants produces streak artifacts in the CT images. These artifacts negate the utility of CT for the spatial localization of PET findings and may propagate through the CT-based attenuation correction into the PET images. In this study, we evaluated the efficacy of an algorithm that reduces metallic artifacts in CT images and the impact of this approach on the quantification of PET images. Methods: Fifty-one patients with and 9 without dental implants underwent a PET/CT study. CT images through the patients dental implants were reconstructed using both standard CT reconstruction and an algorithm that reduces metallic artifacts. Attenuation correction factors were calculated from both sets of CT images and applied to the PET data. The CT images were evaluated for any reduction of the artifacts. The PET images were assessed for any quantitative change introduced by metallic artifact reduction. Results: For each reconstruction, 2 regions of interest were defined in areas where the standard CT reconstruction overestimated the Hounsfield units (HU), 2 were defined in underestimated areas, and 1 was defined in a region unaffected by the artifacts. The 5 regions of interest were transferred to the other 3 reconstructions. Mean HU or mean Bq/cm3 were obtained for all regions. In the CT reconstructions, metallic artifact reduction decreased the overestimated HUs by approximately 60% and increased the underestimated HUs by approximately 90%. There was no change in quantification in the PET images between the 2 algorithms (Spearman coefficient of rank correlation, 0.99). Although the distribution of attenuation (HU) changed considerably in the CT images, the distribution of activity did not change in the PET images. Conclusion: Our study demonstrated that the algorithm can enhance the structural and spatial content of CT images in the presence of metallic artifacts. The CT artifacts do not propagate through the CT-based attenuation correction into the PET images, confirming the robustness of CT-based attenuation correction in the presence of metallic artifacts. The study also demonstrated that considerable changes in CT images do not change the PET images.

PRELIMINARY EVALUATION OF SERIAL 18FDG-PET/CT TO ASSESS RESPONSE TO TOCERANIB PHOSPHATE THERAPY IN CANINE CANCER

Palladia(TM) (toceranib phosphate-Pfizer Animal Health) is a novel orally administered receptor tyrosine kinase inhibitor (TKI) approved for treatment of canine mast cell tumors. Receptor tyrosine kinase dysregulation leads to tumor growth, progression, and metastasis. Toceranibs targets include vascular endothelial growth factor receptor (VEGFR-2/Flk-1/KDR), platelet-derived growth factor receptor, and kit. Positron Emission Tomography/Computed Tomography (PET/CT) is used commonly to diagnose, prognosticate, and monitor response to antineoplastic therapy in human patients. In this study, serial PET/CT imaging with (18) F-fluorodeoxyglucose ((18) FDG) was used to assess response to toceranib therapy in dogs with measurable solid malignancies. Six tumor-bearing dogs underwent tumor assessment using both standard RECIST criteria and PET/CT prior to and at a median of 5 weeks postinitiation of toceranib treatment. Toceranib was prescribed initially at a target dose 3.25 mg/kg PO q48 h, with subsequent modifications based on observed toxicity. Treatment was continued in patients achieving stable disease with acceptable drug tolerance. One dog was maintained on drug despite dose modification due to toxicity; measurable clinical and image-based responses were seen after 10 weeks of therapy. All others had stable or progressive disease based on clinical restaging and PET/CT at first recheck. . Due to discordance with anatomic and metabolic imaging, further studies are needed to investigate the role of molecular imaging in assessment of drug response and identify other potential molecular targets of toceranib.

The Use of Multiple Time Point Dynamic Positron Emission Tomography/Computed Tomography in Patients With Oral/Head and Neck Cancer Does Not Predictably Identify Metastatic Cervical Lymph Nodes

PURPOSE To determine whether the time course of 18-fluorine fluorodeoxyglucose (18F-FDG) activity in multiple consecutively obtained 18F-FDG positron emission tomography (PET)/computed tomography (CT) scans predictably identifies metastatic cervical adenopathy in patients with oral/head and neck cancer. It is hypothesized that the activity will increase significantly over time only in those lymph nodes harboring metastatic cancer. PATIENTS AND METHODS A prospective cohort study was performed whereby patients with oral/head and neck cancer underwent consecutive imaging at 9 time points with PET/CT from 60 to 115 minutes after injection with (18)F-FDG. The primary predictor variable was the status of the lymph nodes based on dynamic PET/CT imaging. Metastatic lymph nodes were defined as those that showed an increase greater than or equal to 10% over the baseline standard uptake values. The primary outcome variable was the pathologic status of the lymph node. RESULTS A total of 2,237 lymph nodes were evaluated histopathologically in the 83 neck dissections that were performed in 74 patients. A total of 119 lymph nodes were noted to have hypermetabolic activity on the 90-minute (static) portion of the study and were able to be assessed by time points. When we compared the PET/CT time point (dynamic) data with the histopathologic analysis of the lymph nodes, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 60.3%, 70.5%, 66.0%, 65.2%, and 65.5%, respectively. CONCLUSIONS The use of dynamic PET/CT imaging does not permit the ablative surgeon to depend only on the results of the PET/CT study to determine which patients will benefit from neck dissection. As such, we maintain that surgeons should continue to rely on clinical judgment and maintain a low threshold for executing neck dissection in patients with oral/head and neck cancer, including those patients with N0 neck designations.

Distribution of 2-deoxy-2-fluoro-d-glucose in the coelom of healthy bald eagles (Haliaeetus leucocephalus).

OBJECTIVE To determine 2-deoxy-2-fluoro (fluorine 18)-d-glucose ((18)FDG) biodistribution in the coelom of bald eagles (Haliaeetus leucocephalus). ANIMALS 8 healthy adult bald eagles. PROCEDURES For each eagle, whole-body transmission noncontrast CT, 60-minute dynamic positron emission tomography (PET) of the celomic cavity (immediately after (18)FDG injection), whole-body static PET 60 minutes after (18)FDG injection, and whole-body contrast CT with iohexol were performed. After reconstruction, images were analyzed. Regions of interest were drawn over the ventricular myocardium, liver, spleen, proventriculus, cloaca, kidneys, and lungs on dynamic and static PET images. Standardized uptake values were calculated. RESULTS Kidneys had the most intense (18)FDG uptake, followed by cloaca and intestinal tract; liver activity was mild and slightly more intense than that of the spleen; proventricular activity was always present, whereas little to no activity was identified in the wall of the ventriculus. Activity in the myocardium was present in all birds but varied in intensity among birds. The lungs had no visibly discernible activity. Mean ± SD standardized uptake values calculated with representative regions of interest at 60 minutes were as follows: myocardium, 1. 6 ± 0.2 (transverse plane) and 1.3 ± 0.3 (sagittal plane); liver, 1.1 ± 0.1; spleen, 0.9 ± 0.1; proventriculus, 1.0 ± 0.1; cloaca, 4.4 ± 2.7; right kidney, 17.3 ± 1.0; left kidney, 17.6 ± 0.3; and right and left lungs (each), 0.3 ± 0.02. CONCLUSIONS AND CLINICAL RELEVANCE The study established the biodistribution of (18)FDG in adult eagles, providing a baseline for clinical investigation and future research.