Practical Tools for Patient-specific Characterization and Dosimetry of Radiopharmaceutical Extravasation.

ABSTRACT: Extravasation during radiopharmaceutical injection may occur with a frequency of more than 10%. In these cases, radioactivity remains within tissue and deposits unintended radiation dose. Characterization of extravasations is a necessary step in accurate dosimetry, but a lack of free and publicly available tools hampers routine standardized analysis. Our objective was to improve existing extravasation characterization and dosimetry methods and to create and validate tools to facilitate standardized practical dosimetric analysis in clinical settings. Using Monte Carlo simulations, we calculated dosimetric values for sixteen nuclear medicine isotopes: 11 C, 64 Cu, 18 F, 67 Ga, 68 Ga, 123 I, 131 I, 111 In, 177 Lu, 13 N, 15 O, 82 Rb, 153 Sm, 89 Sr, 99m Tc, and 90 Y. We validated our simulation results against five logical alternative dose assessment methods. We then created three new characterization tools: a worksheet, a spreadsheet, and a web application. We assessed each tool by recalculating extravasation dosimetry results found in the literature and used each of the tools for patient cases to show clinical practicality. Average variation between our simulation results and alternative methods was 3.1%. Recalculation of published dosimetry results indicated an average error of 7.9%. Time required to use each characterization tool ranged from 1 to 5 min, and agreement between the three tools was favorable. We improved upon existing methods by creating new tools for characterization and dosimetry of radiopharmaceutical extravasation. These free and publicly available tools will enable standardized routine clinical analysis and benefit patient care, clinical follow-up, documentation, and event reporting.

The continual innovation of commercial PET/CT solutions in nuclear cardiology: Siemens Healthineers.

Cardiac PET/CT is an evolving, non-invasive imaging modality that impacts patient management in many clinical scenarios. Beyond offering the capability to assess myocardial perfusion, inflammatory cardiac pathologies, and myocardial viability, cardiac PET/CT also allows for the non-invasive quantitative assessment of myocardial blood flow (MBF) and myocardial flow reserve (MFR). Recognizing the need for an enhanced comprehension of coronary physiology, Siemens Healthineers implemented a sophisticated solution for the calculation of MBF and MFR in 2009. As a result, each aspect of their innovative scanner and image-processing technology seamlessly integrates into an efficient, easy-to-use workflow for everyday clinical use that maximizes the number of patients who potentially benefit from this imaging modality.

Whole-body biodistribution of 3'-deoxy-3'-[(18) f]fluorothymidine ((18) FLT) in healthy adult cats.

Positron emission tomography/computed tomography (PET/CT) utilizing 3'-deoxy-3'-[(18) F]fluorothymidine ((18) FLT), a proliferation tracer, has been found to be a useful tool for characterizing neoplastic diseases and bone marrow function in humans. As PET and PET/CT imaging become increasingly available in veterinary medicine, knowledge of radiopharmaceutical biodistribution in veterinary species is needed for lesion interpretation in the clinical setting. The purpose of this study was to describe the normal biodistribution of (18) FLT in adult domestic cats. Imaging of six healthy young adult castrated male cats was performed using a commercially available PET/CT scanner consisting of a 64-slice helical CT scanner with an integrated whole-body, high-resolution lutetium oxy-orthosilicate (LSO) PET scanner. Cats were sedated and injected intravenously with 108.60 ± 2.09 (mean ± SD) MBq of (18) FLT (greater than 99% radiochemical purity by high-performance liquid chromatography). Imaging was performed in sternal recumbency under general anesthesia. Static images utilizing multiple bed positions were acquired 80.83 ± 7.52 (mean ± SD) minutes post-injection. Regions of interest were manually drawn over major parenchymal organs and selected areas of bone marrow and increased tracer uptake. Standardized uptake values were calculated. Notable areas of uptake included hematopoietic bone marrow, intestinal tract, and the urinary and hepatobiliary systems. No appreciable uptake was observed within brain, lung, myocardium, spleen, or skeletal muscle. Findings from this study can be used as baseline data for future studies of diseases in cats.

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.

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.

Preliminary evaluation of serial (18) FDG-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. Toceranib's 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.

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.

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.

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

UNLABELLED: 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 patient's 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/cm(3) 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.

Positron emission tomography/computerized tomography (PET/CT) scanning for preoperative staging of patients with oral/head and neck cancer.

PURPOSE: To investigate the role of 18-fluorine-fluorodeoxyglucose positron emission tomography/computerized tomography ((18)F-FDG PET/CT) in the preoperative prediction of the presence and extent of neck disease in patients with oral/head and neck cancer. PATIENTS AND METHODS: Seventy patients were enrolled in the study, 47 of whom had a clinically negative neck (N0), 19 of whom had a clinically positive unilateral neck (N+), and 4 of whom were negative on 1 side of the neck and positive on the other. Each patient underwent a PET/CT study before undergoing selective neck dissection for N0 disease or modified radical neck dissection for N+ disease. Tissues were submitted for histopathologic examination and were oriented for the pathologist as to the oncologic levels so as to permit correlation between histopathologic findings and the imaging results. RESULTS: The sensitivity and specificity of the PET/CT procedure were 79% and 82% for the N0 neck, and 95% and 25% for the N+ neck. One hundred ninety-two (11.4%) of the 1,678 nodes identified at histopathology were positive for metastases. The overall nodal sensitivity and specificity were 48% and 99%, respectively. CONCLUSION: In patients with clinically negative necks, a negative test would not help the surgeon in the management strategy of the patient because of the rate of false-negative results, but a positive test can diagnose metastatic deposits with a high positive predictive value. In patients with clinically positive necks, a positive test will confirm the presence of disease, although false-negative lymph nodes were additionally identified in these clinically positive necks. With respect to nodes, the sensitivity of the imaging procedure is such that the results could not help the surgeon in deciding which level to dissect and which to spare. In the final analysis, the head and neck oncologic surgeon should not depend on the results of the PET/CT scan to determine which patients will benefit from neck dissection. Rather, time-honored principles of neck surgery should be followed, particularly with regard to the liberal execution of prophylactic neck dissections in patients with clinically N0 necks.

Time course of early response to chemotherapy in non-small cell lung cancer patients with 18F-FDG PET/CT.

UNLABELLED: PET and (18)F-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 (18)F-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 (18)F-FDG PET studies. (18)F-FDG PET studies performed at 1 and 3 wk after the initiation of chemotherapy allowed prediction of the response to therapy.