Perspectives on joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards for [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors.

Response assessment in the context of immunomodulatory treatments represents a major challenge for the medical imaging community and requires a multidisciplinary approach with involvement of oncologists, radiologists, and nuclear medicine specialists. There is evolving evidence that [18F]FDG PET/CT is a useful diagnostic modality for this purpose. The clinical indications for, and the principal aspects of its standardization in this context have been detailed in the recently published "Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0". These recommendations arose from a fruitful collaboration between international nuclear medicine societies and experts in cancer treatment. In this perspective, the key elements of the initiative are reported, summarizing the core aspects of the guidelines for radiologists and nuclear medicine physicians. Beyond the previous guidelines, this perspective adds further commentary on how this technology can advance development of novel therapeutic approaches and guide management of individual patients.

Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0.

PURPOSE: The goal of this guideline/procedure standard is to assist nuclear medicine physicians, other nuclear medicine professionals, oncologists or other medical specialists for recommended use of [18F]FDG PET/CT in oncological patients undergoing immunotherapy, with special focus on response assessment in solid tumors. METHODS: In a cooperative effort between the EANM, the SNMMI and the ANZSNM, clinical indications, recommended imaging procedures and reporting standards have been agreed upon and summarized in this joint guideline/procedure standard. CONCLUSIONS: The field of immuno-oncology is rapidly evolving, and this guideline/procedure standard should not be seen as definitive, but rather as a guidance document standardizing the use and interpretation of [18F]FDG PET/CT during immunotherapy. Local variations to this guideline should be taken into consideration. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association founded in 1985 to facilitate worldwide communication among individuals pursuing clinical and academic excellence in nuclear medicine. The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote science, technology and practical application of nuclear medicine. The Australian and New Zealand Society of Nuclear Medicine (ANZSNM), founded in 1969, represents the major professional society fostering the technical and professional development of nuclear medicine practice across Australia and New Zealand. It promotes excellence in the nuclear medicine profession through education, research and a commitment to the highest professional standards. EANM, SNMMI and ANZSNM members are physicians, technologists, physicists and scientists specialized in the research and clinical practice of nuclear medicine. All three societies will periodically put forth new standards/guidelines for nuclear medicine practice to help advance the science of nuclear medicine and improve service to patients. Existing standards/guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each standard/guideline, representing a policy statement by the EANM/SNMMI/ANZSNM, has undergone a thorough consensus process, entailing extensive review. These societies recognize that the safe and effective use of diagnostic nuclear medicine imaging requires particular training and skills, as described in each document. These standards/guidelines are educational tools designed to assist practitioners in providing appropriate and effective nuclear medicine care for patients. These guidelines are consensus documents based on current knowledge. They are not intended to be inflexible rules or requirements of practice, nor should they be used to establish a legal standard of care. For these reasons and those set forth below, the EANM, SNMMI and ANZSNM caution against the use of these standards/guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals considering the unique circumstances of each case. Thus, there is no implication that an action differing from what is laid out in the guidelines/procedure standards, standing alone, is below standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the standards/guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines/procedure standards. The practice of medicine involves not only the science, but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible for general guidelines to consistently allow for an accurate diagnosis to be reached or a particular treatment response to be predicted. Therefore, it should be recognized that adherence to these standards/ guidelines will not ensure a successful outcome. All that should be expected is that practitioners follow a reasonable course of action, based on their level of training, current knowledge, clinical practice guidelines, available resources and the needs/context of the patient being treated. The sole purpose of these guidelines is to assist practitioners in achieving this objective. The present guideline/procedure standard was developed collaboratively by the EANM, the SNMMI and the ANZSNM, with the support of international experts in the field. They summarize also the views of the Oncology and Theranostics and the Inflammation and Infection Committees of the EANM, as well as the procedure standards committee of the SNMMI, and reflect recommendations for which the EANM and SNMMI cannot be held responsible. The recommendations should be taken into the context of good practice of nuclear medicine and do not substitute for national and international legal or regulatory provisions.

Factors affecting the repeatability of gamma camera calibration for quantitative imaging applications using a sealed source.

Several applications in nuclear medicine require absolute activity quantification of single photon emission computed tomography images. Obtaining a repeatable calibration factor that converts voxel values to activity units is essential for these applications. Because source preparation and measurement of the source activity using a radionuclide activity meter are potential sources of variability, this work investigated instrumentation and acquisition factors affecting repeatability using planar acquisition of sealed sources. The calibration factor was calculated for different acquisition and geometry conditions to evaluate the effect of the source size, lateral position of the source in the camera field-of-view (FOV), source-to-camera distance (SCD), and variability over time using sealed Ba-133 sources. A small region of interest (ROI) based on the source dimensions and collimator resolution was investigated to decrease the background effect. A statistical analysis with a mixed-effects model was used to evaluate quantitatively the effect of each variable on the global calibration factor variability. A variation of 1 cm in the measurement of the SCD from the assumed distance of 17 cm led to a variation of 1-2% in the calibration factor measurement using a small disc source (0.4 cm diameter) and less than 1% with a larger rod source (2.9 cm diameter). The lateral position of the source in the FOV and the variability over time had small impacts on calibration factor variability. The residual error component was well estimated by Poisson noise. Repeatability of better than 1% in a calibration factor measurement using a planar acquisition of a sealed source can be reasonably achieved. The best reproducibility was obtained with the largest source with a count rate much higher than the average background in the ROI, and when the SCD was positioned within 5 mm of the desired position. In this case, calibration source variability was limited by the quantum noise.

EQPlanar: a maximum-likelihood method for accurate organ activity estimation from whole body planar projections.

Optimizing targeted radionuclide therapy requires patient-specific estimation of organ doses. The organ doses are estimated from quantitative nuclear medicine imaging studies, many of which involve planar whole body scans. We have previously developed the quantitative planar (QPlanar) processing method and demonstrated its ability to provide more accurate activity estimates than conventional geometric-mean-based planar (CPlanar) processing methods using physical phantom and simulation studies. The QPlanar method uses the maximum likelihood-expectation maximization algorithm, 3D organ volume of interests (VOIs), and rigorous models of physical image degrading factors to estimate organ activities. However, the QPlanar method requires alignment between the 3D organ VOIs and the 2D planar projections and assumes uniform activity distribution in each VOI. This makes application to patients challenging. As a result, in this paper we propose an extended QPlanar (EQPlanar) method that provides independent-organ rigid registration and includes multiple background regions. We have validated this method using both Monte Carlo simulation and patient data. In the simulation study, we evaluated the precision and accuracy of the method in comparison to the original QPlanar method. For the patient studies, we compared organ activity estimates at 24 h after injection with those from conventional geometric mean-based planar quantification using a 24 h post-injection quantitative SPECT reconstruction as the gold standard. We also compared the goodness of fit of the measured and estimated projections obtained from the EQPlanar method to those from the original method at four other time points where gold standard data were not available. In the simulation study, more accurate activity estimates were provided by the EQPlanar method for all the organs at all the time points compared with the QPlanar method. Based on the patient data, we concluded that the EQPlanar method provided a substantial increase in accuracy of organ activity estimates from 24 h planar images compared to the CPlanar using 24 h SPECT as the golden standard. For other time points, where no golden standard is available, better agreement between estimated and measured projections was observed by using the EQPlanar method compared to the QPlanar method. This phenomenon is consistent with the improvement in goodness of fit seen in both simulation data and 24 h patient data. Therefore, this indicates the improved reliability of organ activity estimates obtained though the EQPlanar method.

Molecular imaging in thyroid cancer.

Molecular imaging plays an important role in the evaluation and management of thyroid cancer. The routine use of thyroid scanning in all thyroid nodules is no longer recommended by many authorities. In the initial work-up of a thyroid nodule, radioiodine imaging can be particularly helpful when the thyroid stimulating hormone level is low and an autonomously functioning nodule is suspected. Radioiodine imaging can also be helpful in the 10-15% of cases for which fine-needle aspiration biopsy is indeterminate. Therapy of confirmed thyroid cancer frequently involves administration of iodine-131 after surgery to ablate remnant tissue. In the follow-up of thyroid cancer patients, increased thyroglobulin levels will often prompt the empiric administration of 131I followed by whole body radioiodine imaging in the search for recurrent or metastatic disease. 131I imaging of the whole body and blood pharmacokinetics can be used to determine if higher doses of 131I can be given in thyroid cancer. The utility of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is steadily increasing. FDG is primarily taken up by dedifferentiated thyroid cancer cells, which are poorly iodine avid. Thus, it is particularly helpful in the patient with an increased thyroglobulin but negative radioiodine scan. FDG PET is also useful in the patient with a neck mass but unknown primary, in patients with aggressive (dedifferentiated) thyroid cancer, and in patients with differentiated cancer where histologic transformation to dedifferentiation is suspected. In rarer types of thyroid cancer, such as medullary thyroid cancer, FDG and other tracers such as 99mTc sestamibi, [11C]methionine, [111In]octreotide, and [68Ga]somatostatin receptor binding reagents have been utilized. 124I is not widely available, but has been used for PET imaging of thyroid cancer and will likely see broader applicability due to the advantages of PET methodology.

Follow-up of low-risk differentiated thyroid cancer patients who underwent radioiodine ablation of postsurgical thyroid remnants after either recombinant human thyrotropin or thyroid hormone withdrawal.

BACKGROUND: We previously demonstrated comparable thyroid remnant ablation rates in postoperative low-risk thyroid cancer patients prepared for administration of 3.7GBq (131)I (100 mCi) after recombinant human (rh) TSH during T(4) (L-T4) therapy vs. withholding L-T4 (euthyroid vs. hypothyroid groups). We now compared the outcomes of these patients 3.7 yr later. PATIENTS AND METHODS: Fifty-one of the 63 original patients (28 euthyroid, 23 hypothyroid) participated. Forty-eight received rhTSH and serum thyroglobulin (Tg) sampling. A (131)I whole-body scan was performed in 43 patients, and successful ablation was defined by criteria from the previous study. Based on the criterion of uptake less than 0.1% in thyroid bed, 100% (43 of 43) remained ablated. When no visible uptake instead was used, five patients (four euthyroid, one hypothyroid) had minimal visible activity. When the TSH-stimulated Tg criterion was used, only two of 45 (one euthyroid, one hypothyroid) had a stimulated Tg level greater than 2 ng/ml. RESULTS: No patient in either group died, and no patient declared disease free had sustained tumor recurrence. Nine (four euthyroid, five hypothyroid) had received additional (131)I between the original and current studies due to detectable Tg or imaging evidence of disease; with follow-up, all now had a negative rhTSH-stimulated whole-body scan and seven (three euthyroid, four hypothyroid) had a stimulated serum Tg less than 2 ng/ml. CONCLUSIONS: In conclusion, after a median 3.7 yr, low-risk thyroid cancer patients prepared for postoperative remnant ablation either with rhTSH or after L-T4 withdrawal were confirmed to have had their thyroid remnants ablated and to have comparable rates of tumor recurrence and persistence.

Assessment of the incremental value of recombinant thyrotropin stimulation before 2-[18F]-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography imaging to localize residual differentiated thyroid cancer.

PURPOSE: The purpose of the study was to assess prospectively the impact of recombinant human TSH (rhTSH) administration on positron emission tomography (PET)/computed tomography (CT) imaging in differentiated thyroid cancer patients who, after primary treatment, had a suppressed or stimulated serum thyroglobulin greater than 10 ng/ml and no radioactive iodine uptake consistent with thyroid cancer on a whole body scan. PATIENTS AND METHODS: PET/CT was performed before (basal PET) and 24-48 h after rhTSH administration (rhTSH-PET) in 63 patients (52 papillary and 11 follicular thyroid cancers). Images were blindly analyzed by two readers. The proposed treatment plan was prospectively assessed before basal PET, after basal PET, and again after rhTSH-PET. RESULTS: A total of 108 lesions were detected in 48 organs in 30 patients. rhTSH-PET was significantly more sensitive than basal PET for the detection of lesions (95 vs. 81%; P = 0.001) and tended to be more sensitive for the detection of involved organs (94 vs. 79%; P = 0.054). However, basal PET and rhTSH-PET did not have significantly different sensitivity for detecting patients with any lesions (49 vs. 54%; P = 0.42). Changes in treatment management plan occurred in 19% of the patients after basal PET. Lesions found only by rhTSH-PET contributed to an altered therapeutic plan in eight patients, among whom only four were true-positive on pathology (6%). CONCLUSION: The use of rhTSH for 2-[18F]-fluoro-2-deoxy-D-glucose-PET/CT significantly increased the number of lesions detected, but the numbers of patients in whom any lesion was detected were no different between basal and rhTSH-stimulated PET/CT scans. Treatment changes due to true positive lesions occurred in 6% of cases.

Comparison of residence time estimation methods for radioimmunotherapy dosimetry and treatment planning--Monte Carlo simulation studies.

Estimating the residence times in tumor and normal organs is an essential part of treatment planning for radioimmunotherapy (RIT). This estimation is usually done using a conjugate view whole body scan time series and planar processing. This method has logistical and cost advantages compared to 3-D imaging methods such as Single photon emission computed tomography (SPECT), but, because it does not provide information about the 3-D distribution of activity, it is difficult to fully compensate for effects such as attenuation and background and overlapping activity. Incomplete compensation for these effects reduces the accuracy of the residence time estimates. In this work we compare residence times estimates obtained using planar methods to those from methods based on quantitative SPECT (QSPECT) reconstructions. We have previously developed QSPECT methods that provide compensation for attenuation, scatter, collimator-detector response, and partial volume effects. In this study we compared the use of residence time estimation methods using QSPECT to planar methods. The evaluation was done using the realistic NCAT phantom with organ time activities that model (111)In ibritumomab tiuxetan. Projection data were obtained using Monte Carlo simulations (MCS) that realistically model the image formation process including penetration and scatter in the collimator-detector system. These projection data were used to evaluate the accuracy of residence time estimation using a time series of QSPECT studies, a single QSPECT study combined with planar scans and the planar scans alone. The errors in the residence time estimates were 3.8%, 15%, and 2%-107% for the QSPECT, hybrid planar/QSPECT, and planar methods, respectively. The quantitative accuracy was worst for pure planar processing and best for pure QSPECT processing. Hybrid planar/QSPECT methods, where a single QSPECT study was combined with a series of planar scans, provided a large and statistically significant improvement in quantitative accuracy for most organs compared to the planar scans alone, even without sophisticated attention to background subtraction or thickness corrections in planar processing. These results indicate that hybrid planar/QSPECT methods are generally superior to pure planar methods and may be an acceptable alternative to performing a time series of QSPECT studies.

Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study.

CONTEXT: After surgery for differentiated thyroid carcinoma, many patients are treated with radioiodine to ablate remnant thyroid tissue. This procedure has been performed with the patient in the hypothyroid state to promote endogenous TSH stimulation and is often associated with hypothyroid symptoms and impaired quality of life. OBJECTIVE AND INTERVENTION: This international, randomized, controlled, multicenter trial aimed to compare the efficacy and safety of recombinant human TSH (rhTSH) to prepare euthyroid patients on L-thyroxine therapy (euthyroid group) to ablate remnant thyroid tissue with 3.7 GBq (100 mCi) 131I, compared with that with conventional remnant ablation performed in the hypothyroid state (hypothyroid group). Quality of life was determined at the time of randomization and ablation. After the administration of the 131-I dose, the rate of radiation clearance from blood, thyroid remnant, and whole body was measured. RESULTS: The predefined primary criterion for successful ablation was "no visible uptake in the thyroid bed, or if visible, fractional uptake less than 0.1%" on neck scans performed 8 months after therapy and was satisfied in 100% of patients in both groups. A secondary criterion for ablation, an rhTSH-stimulated serum thyroglobulin concentration less than 2 ng/ml, was fulfilled by 23 of 24 (96%) euthyroid patients and 18 of 21 (86%) hypothyroid patients (P = 0.2341). Quality of life was well preserved in the euthyroid group, compared with the hypothyroid group, as demonstrated by their lower pretreatment scores on the Billewicz scale for hypothyroid signs and symptoms, 27 +/- 7 vs. 18 +/- 4 (P < 0.0001) and their significantly higher Short Form-36 Health Assessment Scale scores in five of eight categories. Euthyroid patients had a statistically significant one third lower radiation dose to the blood, compared with patients in the hypothyroid group. CONCLUSIONS: This study demonstrates comparable remnant ablation rates in patients prepared for 131I remnant ablation with 3.7 GBq by either administering rhTSH or withholding thyroid hormone. rhTSH-prepared patients maintained a higher quality of life and received less radiation exposure to the blood.

Radionuclide imaging metabolic activity of brown adipose tissue in a patient with pheochromocytoma.

We describe a patient with extra-adrenal pheochromocytoma and high plasma norepinephrine levels. Radionuclide images of this patient obtained using (18)F-fluorodeoxyglucose and (123)I-metaiodobenzylguanidine revealed bilateral tracer accumulation in the shoulder and lower neck. The regions of radiotracer uptake corresponded to the location of human brown adipose tissue (BAT). Excessive sympathetic stimulation by high circulating catecholamine concentrations augmented the metabolic activity and tracer uptake in the BAT. This study showed that radionuclide imaging can noninvasively visualize human BAT in terms of metabolic and functional activity.

PET-CT detection of abdominal recurrence of ovarian cancer: radiologic-surgical correlation.

The diagnosis of recurrent ovarian cancer can be difficult on cross-sectional imaging, and variable sensitivities and specificities have been reported for positron emission tomography (PET). Combined functional and anatomic imaging with PET plus computed tomography (CT) potentially allows for improved detection of tumor masses. We investigated the sensitivity, specificity, and accuracy of PET-CT for the diagnosis of recurrent ovarian cancer. Sixteen women with previously treated ovarian cancer underwent imaging on a combined PET-CT scanner followed by surgery to assess for possible recurrent disease. The fused PET-CT images were retrospectively reviewed for recurrent disease, and the results of PET-CT were compared with the operative notes. Eleven of the 16 patients had recurrent disease at surgery. The sensitivity, specificity, and accuracy of PET-CT for disease detection on a per-patient basis were 72.7%, 40%, and 62.5%, respectively. For cases of malignant adenopathy (n = 7), 100% were detected on PET-CT. For peritoneal lesions no larger than 1 cm (n = 23), 13% were detected on PET-CT. For peritoneal lesions larger than 1 cm (n = 8), 50% were detected on PET-CT. The sensitivity of PET-CT for recurrent ovarian cancer is moderate in patients with low volume disease. A trial involving a larger number of patients with a spectrum of disease volumes is necessary to determine the impact of PET-CT in clinical practice.

Imaging of neuroendocrine tumors: accuracy of helical CT versus SRS.

BACKGROUND: We retrospectively compared the accuracy of somatostatin receptor scintigraphy (SRS) with that of helical computed tomography (CT) in the detection and localization of primary and metastatic neuroendocrine tumors. METHODS: A medical record search identified 27 patients with known or clinically suspected neuroendocrine tumors who underwent helical CT and SRS within 3 months of one another at our institution. CT images were evaluated retrospectively by two blinded radiologists who used consensus reading. Images were evaluated for the presence or absence of primary tumor and hepatic and extrahepatic metastases. CT results were compared with the SRS report as interpreted by the nuclear medicine physicians. The results of the surgical, clinical follow-up, and pathologic findings were considered as the gold standard. Sensitivity, specificity, and accuracy were calculated for both imaging techniques. In addition, McNemar analysis was performed to determine statistically significant differences between CT and SRS. RESULTS: Helical CT was more sensitive than SRS in the detection of extrahepatic metastases, and the difference between the two imaging modalities was statistically significant (p = 0.0312) as determined by the McNemar chi-square test. However, the difference between CT and SRS in detecting primary neuroendocrine tumors, hepatic metastasis, and combined hepatic and extrahepatic metastasis was not statistically significant (p = 0.625, 1.000, and 1.000, respectively). CONCLUSION: Helical CT and SRS have similar sensitivity, specificity, and accuracy in detecting primary neuroendocrine tumor and hepatic metastasis. However, helical CT appears to be more sensitive in detecting extrahepatic metastasis from primary neuroendocrine tumors.

Incremental value of CT in PET/CT of patients with colorectal carcinoma.

BACKGROUND: We assessed the contribution of dedicated computed tomographic (CT) interpretation to the accuracy of positron emission tomography (PET) plus CT in imaging patients with suspected primary or metastatic colorectal carcinoma. METHODS: One hundred PET/CT scans in 90 consecutive patients were evaluated retrospectively. Imaging was performed on a GE Discovery LS PET/CT scanner. PET images were obtained from the skull base through the midthigh after intravenous administration of 15 to 20 mCi of [(18)F] fluorine-18-fluoro-2-deoxyglucose. Noncontrast axial CT images were obtained at the same anatomic locations, with 140 kV, 80 mA, 0.8 s/CT rotation, a pitch of 6, and a table speed of 22.5 mm/s. The CT component of the PET/CT study was reviewed independently by consensus of two blinded readers. Scans were evaluated for the presence of primary disease, local recurrence, and distant metastases. Results were compared with the PET/CT report. The gold standard was clinical and imaging follow-up for at least 6 months, surgery, or biopsy. RESULTS: The study included 40 males and 50 females, with a mean age of 63 years (range, 31-92 years). The indications for the examination were to evaluate for recurrence of colorectal cancer in 83 cases, determine disease spread in 15 cases, and evaluate for possible primary malignancy in two cases with rising carcinoembryonic antigen. Sensitivity, specificity, and accuracy of the PET/CT report and of the combined PET/CT with dedicated CT interpretation were 0.914, 0.633, and 0.830 and 0.986, 1.000, and 0.980, respectively. The difference between PET/CT and the combined PET/CT with dedicated CT interpretation with respect to accuracy was statistically significant (p < 0.05). CONCLUSION: The CT portion of PET/CT provides valuable anatomic and pathologic information to the functional information provided by PET and helps improve the overall accuracy of the combined study.

18F-Fluoro-2-deoxyglucose positron emission tomography in the evaluation of gastrointestinal malignancies.

Positron emission tomography with (18)F-fluoro-2-deoxyglucose is an imaging technology that is demonstrating increasing utility in the evaluation of gastrointestinal malignancies.

Radiology of colorectal cancer.

In the past 20 years, the radiology of colorectal cancer has evolved from the barium enema to advanced imaging modalities like phased array magnetic resonance imaging (MRI), virtual colonoscopy and positron emission tomography (PET). Nowadays, primary rectal cancers are preferably imaged with transrectal ultrasound or MRI, while barium enema is still the most often used technique for imaging of colonic cancers. Virtual colonoscopy is rapidly evolving and might considerably change the imaging of colorectal cancer in the near future. The use of virtual colonoscopy for screening purposes and imaging of the colon in occlusive cancer or incomplete colonoscopies is currently under evaluation. The main role of PET is in detecting tumour recurrences, both locally and distantly. Techniques to fuse cross-sectional anatomical (computer tomography (CT) and MRI) and functional (PET) images are being developed. Apart from diagnostic imaging, the radiologists has added image-guided minimally invasive treatments of colorectal liver metastases to their arsenal. The radio-frequency ablation technique is now widely available, and can be used during laparotomy or percutaneously in selected cases.

Is enteral administration of fluorine-18-fluorodeoxyglucose (F-18 FDG) a palatable alternative to IV injection? Pre-clinical evaluation in normal rodents.

To establish effective methods of enteral 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) administration, the efficiency of FDG absorption in the gastrointestinal tracts following enteral administrations was evaluated using the FDG biodistribution in normal rodents, in combination with various fasting conditions and FDG diluents. The blood FDG curve using hypotonic solution showed a rapid increase, while that in iso- and hypertonic groups showed slow rises. Brain FDG uptake had a close positive correlation with blood AUC (area under curve) and an inverse relationship with the stomach contents.

Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas.

PURPOSE: To evaluate the efficacy and safety of tositumomab and iodine I 131 tositumomab (Bexxar; Corixa Corp, Seattle, WA, and GlaxoSmithKline, Philadelphia, PA) in patients with chemotherapy-refractory low-grade or transformed low-grade non-Hodgkin's lymphoma (NHL) and to compare its efficacy to the patients' last qualifying chemotherapy (LQC) regimens. PATIENTS AND METHODS: Sixty patients who had been treated with at least two protocol-specified qualifying chemotherapy regimens and had not responded or progressed within 6 months after their LQC were treated with a single course of iodine I 131 tositumomab. RESULTS: Patients had received a median of four prior chemotherapy regimens. A partial or complete response (CR) was observed in 39 patients (65%) after iodine I 131 tositumomab, compared with 17 patients (28%) after their LQC (P <.001). The median duration of response (MDR) was 6.5 months after iodine I 131 tositumomab, compared with 3.4 months after the LQC (P <.001). Two patients (3%) had a CR after their LQC, compared with 12 (20%) after iodine I 131 tositumomab (P <.001). The MDR for CR was 6.1 months after the LQC and had not been reached with follow-up of more than 47 months after iodine I 131 tositumomab. An independent review panel verified that 32 (74%) of the 43 patients with nonequivalent durations of response (> 30 days difference) had a longer duration of response after iodine I 131 tositumomab (P <.001). Only one patient was hospitalized for neutropenic fever. Five patients (8%) developed human antimurine antibodies, and one (2%) developed an elevated TSH level after treatment. Myelodysplasia was diagnosed in four patients in follow-up. CONCLUSION: A single course of iodine I 131 tositumomab was significantly more efficacious than the LQC received by extensively pretreated patients with chemotherapy-refractory, low-grade, or transformed low-grade NHL and had an acceptable safety profile.

Sentinel node localization in oral cavity and oropharynx squamous cell cancer.

OBJECTIVE: To evaluate the feasibility and predictive ability of the sentinel node localization technique for patients with squamous cell carcinoma of the oral cavity or oropharynx and clinically negative necks. DESIGN: Prospective, efficacy study comparing the histopathologic status of the sentinel node with that of the remaining neck dissection specimen. SETTING: Tertiary referral center. PATIENTS: Patients with T1 or T2 disease and clinically negative necks were eligible for the study. Nine previously untreated patients with oral cavity or oropharyngeal squamous cell carcinoma were enrolled in the study. INTERVENTIONS: Unfiltered technetium Tc 99m sulfur colloid injections of the primary tumor and lymphoscintigraphy were performed on the day before surgery. Intraoperatively, the sentinel node(s) was localized with a gamma probe and removed after tumor resection and before neck dissection. MAIN OUTCOME MEASURES: The primary outcome was the negative predictive value of the histopathologic status of the sentinel node for predicting cervical metastases. RESULTS: Sentinel nodes were identified in 9 previously untreated patients. In 5 patients, there were no positive nodes. In 4 patients, the sentinel nodes were the only histopathologically positive nodes. In previously untreated patients, the sentinel node technique had a negative predictive value of 100% for cervical metastasis. CONCLUSIONS: Our preliminary investigation shows that sentinel node localization is technically feasible in head and neck surgery and is predictive of cervical metastasis. The sentinel node technique has the potential to decrease the number of neck dissections performed in clinically negative necks, thus reducing the associated morbidity for patients in this group.

Current status of PET in breast cancer imaging, staging, and therapy.

The exact roles of PET in the imaging management of patients with known or suspected breast cancer are still in evolution. For assessing primary lesions, it is sometimes possible with PET to detect cancers occult on standard methods. This could be useful in high-risk patient populations, but in dense breasts, background FDG uptake is often higher than in women with fatty breasts, making identification of lesions < 1 cm in size improbable with current technologies. Distinguishing malignant from benign primary breast disease would seem better addressed by biopsy. With a positive predictive value of FDG PET for cancer over 96%, any FDG-avid breast lesion is highly suspicious and merits biopsy. Although PET in theory should be useful for depicting multifocal disease before surgery, the limitations in detecting small lesions in the breast limit the contribution of PET at present. It is most likely that PET will have a greater role in depicting primary breast lesions as dedicated PET imaging devices for the breast evolve. For axillary and internal mammary nodal staging, results with FDG PET are variable. Small nodal metastases < or = 5 mm will be missed by PET, whereas larger ones are more likely to be detected. PET can depict internal mammary nodes, but the accuracy of the method in this setting is not known, nor is there consensus on how identifying internal mammary node metastases will change treatment. Based on the available data, for pT1 breast lesions, PET, if negative, is not an adequate replacement for sentinel node surgery or axillary dissection. Results from the multicenter trial will be of great interest. Clearly PET can stage metastatic disease well. Bone scans with 18F- are exquisitely sensitive for metastases, and FDG is also very good. However, FDG PET can miss some blastic metastases to bone so at present FDG is not capable of excluding the presence of bone metastases. PET seems very well suited to detecting recurrences in soft tissues and the brachial plexus region in particular. The utility of PET in planning the treatment of individual patients appears promising. Although results must be confirmed in larger studies, it appears safe to conclude that failure of a chemotherapy regimen to decrease FDG uptake promptly in a breast cancer portends poor response. This does not hold true for hormonal therapy. At present, labeled estrogens are not widely available and cannot be recommended for clinical use. Thus, PET has shown considerable promise in breast cancer imaging, but in the author's experience is best applied to solve difficult imaging questions in specific patients and is not recommended for routine evaluation of the breast cancer patient. However, in larger primary tumors, the ability to use PET for staging and to plan treatment response suggest it will be more widely used. Additional studies with newer PET imaging devices and FDG and other tracers will help us better determine the role of PET in routine clinical care of the patient with known or suspected breast cancer. Certainly, this represent a fertile area for translational research studies over the next several years with the potential to significantly alter the way breast cancer is imaged and managed.