NCCN Task Force Report: Bone Health In Cancer Care.

Bone health and maintenance of bone integrity are important components of comprehensive cancer care. Many patients with cancer are at risk for therapy-induced bone loss, with resultant osteoporotic fractures, or skeletal metastases, which may result in pathologic fractures, hypercalcemia, bone pain, and decline in motility and performance status. Effective screening and timely interventions are essential for reducing bone-related morbidity. Management of long-term bone health requires a broad knowledge base. A multidisciplinary health care team may be needed for optimal assessment and treatment of bone-related issues in patients with cancer. Since publication of the previous NCCN Task Force Report: Bone Health in Cancer Care in 2009, new data have emerged on bone health and treatment, prompting NCCN to convene this multidisciplinary task force to discuss the progress made in optimizing bone health in patients with cancer. In December 2012, the panel members provided didactic presentations on various topics, integrating expert judgment with a review of the key literature. This report summarizes issues surrounding bone health in cancer care presented and discussed during this NCCN Bone Health in Cancer Care Task Force meeting.

Multimodality therapy: bone-targeted radioisotope therapy of prostate cancer.

Accumulating data suggest that bone-seeking radiopharmaceuticals can be used to treat prostate cancer bone metastasis and improve the clinical outcome of patients with advanced prostate cancer. It remains to be elucidated whether radiopharmaceuticals enhance the disruption of the onco-niche or the eradication of micrometastatic cells in the bone marrow. The purpose of this review is to investigate the role of bone-targeted radioisotope therapy in the setting of multimodality therapy for advanced prostate cancer. We examine available data and evaluate whether dose escalation, newer generations, or repeated dosing of radiopharmaceuticals enhance their antitumor effects and whether their combination with hormone ablative therapy, chemotherapy, or novel targeted therapy can improve clinical efficacy.

Radiation dosimetry and biodistribution of (99m)Tc-ethylene dicysteine-deoxyglucose in patients with non-small-cell lung cancer.

PURPOSE: To assess the radiation dosimetry and biodistribution of (99m)Tc-labeled ethylene dicysteine deoxyglucose ((99m)Tc-EC-DG) in patients with non-small-cell lung cancer (NSCLC). METHODS: Serial whole-body scans were acquired 0, 2, 4, 6 and 24 h after injection of (99m)Tc-EC-DG (925 MBq) in seven NSCLC patients. Radiation dosimetry, blood clearance and SPECT imaging of the primary tumor were assessed. RESULTS: The critical organ was the bladder wall, with average radiation absorbed dose over all seven patients of 2.47x10(-2) mGy/MBq. The average effective dose equivalent and effective dose were 6.20x10(-3) mSv/MBq (6.89 mSv/1,110 MBq) and 5.90x10(-3) mSv/MBq (6.54 mSv/1,110 MBq), respectively. The primary tumor was visualized with SPECT in six patients. On final pathology, one patient had a granuloma, which did not enhance with (99m)Tc-EC-DG. CONCLUSION: (99m)Tc-EC-DG has acceptable dosimetric and biodistribution properties as a diagnostic tumor-imaging agent. Future studies are planned to evaluate its diagnostic potential.

PET and PET/CT in management of the lymphomas.

Within recent years, F-18 fluorodeoxyglucose (FDG) PET has become the most important nuclear medicine and radiology imaging modality in the management of lymphoma. FDG-PET detects more disease sites and involved organs than conventional staging procedures, including CT, and has a large influence on staging. FDG-PET performed during and after therapy seems to provide considerable prognostic information. The impact on patient outcome is not clear, however, because no controlled trials have yet been conducted and follow-up periods are generally short.

Therapy tolerance in selected patients with androgen-independent prostate cancer following strontium-89 combined with chemotherapy.

PURPOSE: Clinicians may have reservations about using strontium-89 for the treatment of bone metastases because of concerns that it may limit future use of chemotherapy. We assessed the rate of bone marrow failure in patients with prostate cancer who had received a dose of strontium-89. PATIENTS AND METHODS: This subgroup analysis involved 34 patients with androgen-independent prostate cancer who had been given a dose of strontium-89 and six weekly doses of doxorubicin after response to induction chemotherapy. We assessed subsequent hematotoxicity in terms of bone marrow failure and the ability to tolerate additional treatments during a median of 25 months (range, 7 to 76 months) after the strontium-89 was administered. RESULTS: No patients developed bone marrow failure within 6 months of receiving strontium-89. Five (15%) of 34 patients developed bone marrow failure at a median 23 months (range, 6 to 53 months) after the strontium-89 treatment. Bone marrow biopsy performed in two of these five patients showed complete replacement of the marrow by tumor. Thirty-one patients (91%) received subsequent cytotoxic treatments at a median 11 months (range, 1 to 33 months) after the strontium-89 treatment. CONCLUSION: This analysis demonstrated that a single dose of strontium-89 combined with chemotherapy did not affect the delivery of subsequent courses of chemotherapy in a select group of patients. However, a majority of these therapies were given off protocol and were administered at a dose schedule that might be considered inappropriate or inadequate. The clinical role and safety profile of radiopharmaceuticals combined with chemotherapy in prostate cancer therapy deserve further exploration.

[18F]fluorodeoxyglucose uptake by positron emission tomography predicts outcome of non-small-cell lung cancer.

PURPOSE: To determine whether the standardized uptake value (SUV) of [(18)F]fluorodeoxyglucose uptake by positron emission tomography could be a prognostic factor for non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred sixty-two patients with stage I to IIIb NSCLC were analyzed. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local-regional control (LRC) were calculated by the Kaplan-Meier method and evaluated with the log-rank test. The prognostic significance was assessed by univariate and multivariate analyses. RESULTS: There were 93 patients treated with surgery and 69 patients treated with radiotherapy. A cutoff of 5 for the SUV for the primary tumor showed the best discriminative value. The SUV for the primary tumor was a significant predictor of OS (P = .02) in both groups. Low SUVs ( 5.0; surgery group, P = .02; radiotherapy group, P = .0005). Low SUVs ( 5.0; stage I or II, P = .02; stage IIIa or IIIb, P = .004). However, using the same cutoff point of 5, the SUV for regional lymph nodes was not a significant indicator for DFS (P = .19), LRC (P = .97), or DMFS (P = .17). The multivariate analysis showed that the SUV for the primary tumor was a significant prognostic factor for OS (P = .03) and DFS (P = .001). CONCLUSION: The SUV of the primary tumor was the strongest prognostic factor among the patients treated by curative surgery or radiotherapy.

American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer.

PURPOSE: To develop a guideline for the use of sentinel node biopsy (SNB) in early stage breast cancer. METHODS: An American Society of Clinical Oncology (ASCO) Expert Panel conducted a systematic review of the literature available through February 2004 on the use of SNB in early-stage breast cancer. The panel developed a guideline for clinicians and patients regarding the appropriate use of a sentinel lymph node identification and sampling procedure from hereon referred to as SNB. The guideline was reviewed by selected experts in the field and the ASCO Health Services Committee and was approved by the ASCO Board of Directors. RESULTS: The literature review identified one published prospective randomized controlled trial in which SNB was compared with axillary lymph node dissection (ALND), four limited meta-analyses, and 69 published single-institution and multicenter trials in which the test performance of SNB was evaluated with respect to the results of ALND (completion axillary dissection). There are currently no data on the effect of SLN biopsy on long-term survival of patients with breast cancer. However, a review of the available evidence demonstrates that, when performed by experienced clinicians, SNB appears to be a safe and acceptably accurate method for identifying early-stage breast cancer without involvement of the axillary lymph nodes. CONCLUSION: SNB is an appropriate initial alternative to routine staging ALND for patients with early-stage breast cancer with clinically negative axillary nodes. Completion ALND remains standard treatment for patients with axillary metastases identified on SNB. Appropriately identified patients with negative results of SNB, when done under the direction of an experienced surgeon, need not have completion ALND. Isolated cancer cells detected by pathologic examination of the SLN with use of specialized techniques are currently of unknown clinical significance. Although such specialized techniques are often used, they are not a required part of SLN evaluation for breast cancer at this time. Data suggest that SNB is associated with less morbidity than ALND, but the comparative effects of these two approaches on tumor recurrence or patient survival are unknown.

Incidental findings on integrated PET/CT that do not accumulate 18F-FDG.

OBJECTIVE: The purpose of this study was to report the prevalence of abnormalities that do not show increased 18F-FDG uptake on the CT component of integrated PET/CT in patients with non-small cell lung cancer. MATERIALS AND METHODS: Images from all PET/CT studies performed consecutively between April and October 2003 on patients with non-small cell lung cancer were retrospectively reviewed. All abnormalities present on the CT component of the PET/CT scans that did not show abnormally increased 18F-FDG uptake were documented. RESULTS: Three hundred twenty-one patients with non-small cell lung cancer (179 men, 142 women; mean age, 67 years; age range, 38-91 years) underwent initial staging (198/321 [62%]) or restaging (123/321 [38%]) PET/CT imaging during the study period. In 263 (82%) of the patients, CT showed 1,231 abnormalities that were not 18F-FDG avid. The abnormalities were located in the thorax (n = 650), abdomen and pelvis (n = 444), head and neck (n = 69), and bony skeleton (n = 68). In total, 298 (24%) of the abnormalities that were not 18F-FDG avid were located outside the range of a standard thoracic CT scan. The clinical importance of these abnormalities was classified as major (n = 48 [4%]), moderate (n = 465 [38%]), or minor (n = 718 [58%]). Four (1%) of the patients had findings of major clinical importance that did not show increased 18F-FDG uptake and were previously unsuspected. CONCLUSION: Among patients with non-small cell lung cancer undergoing PET/CT, there is a high prevalence of CT abnormalities that do not show correlative 18F-FDG avidity but that may be clinically important.

Truncation artifact on PET/CT: impact on measurements of activity concentration and assessment of a correction algorithm.

OBJECTIVE: Discrepancy between fields of view (FOVs) in a PET/CT scanner causes a truncation artifact when imaging extends beyond the CT FOV. The purposes of this study were to evaluate the impact of this artifact on measurements of 18F-FDG activity concentrations and to assess a truncation correction algorithm. MATERIALS AND METHODS: Two phantoms and five patients were used in this study. In the first phantom, three inserts (water, air, bone equivalent) were placed in a water-filled cylinder containing 18F-FDG. In the second phantom study, a chest phantom and a 2-L bottle fitted with a bone insert were used to simulate a patient's torso and arm. Both phantoms were imaged while positioned centrally (baseline) and at the edge of the CT FOV to induce truncation. PET images were reconstructed using attenuation maps from truncated and truncation-corrected CT images. Regions of interest (ROIs) drawn on the inserts, simulated arm, and background water of the baseline truncated and truncation-corrected PET images were compared. In addition, extremity malignancies of five patients truncated on CT images were reconstructed with and without correction and the maximum standard uptake values (SUVs) of the malignancies were compared. RESULTS: Truncation artifact manifests as a rim of high activity concentration at the edge of the truncated CT image with an adjacent low-concentration region peripherally. The correction algorithm minimizes these effects. Phantom studies showed a maximum variation of -5.4% in the truncation-corrected background water image compared with the baseline image. Activity concentration in the water insert was 6.3% higher while that of air and bone inserts was similar to baseline. Extremity malignancies showed a consistent increase in the maximum SUV after truncation correction. CONCLUSION: Truncation affects measurements of 18F-FDG activity concentrations in PET/CT. A truncation-correction algorithm corrects truncation artifacts with small residual error.

Interobserver and intraobserver variability of standardized uptake value measurements in non-small-cell lung cancer.

OBJECTIVES: To assess interobserver and intraobserver variabilities in measuring the maximal standardized uptake value (SUV) of non-small-cell lung cancer. METHODS: Positron emission tomography-computed tomography examinations of 20 consecutive patients referred for initial evaluation of newly diagnosed non-small-cell lung cancer were retrospectively reviewed by 5 experienced positron emission tomography-computed tomography readers, who independently measured the maximal SUV/body weight of the primary tumors. Interobserver and intraobserver variabilities were assessed by using 4 statistical methods: correlation, regression analysis, Bland-Altman analysis, and analysis of variance. The SUV measurements derived in the study were compared with the SUV measurements documented in the original reports using correlation and regression analysis. The percentages of tumors whose retrospective SUV measurements were more than 20% different and more than 25% different from those in the original report were assessed. RESULTS: Both interobserver and intraobserver SUV measurements were highly reproducible. Pearson correlation coefficients were greater than 0.95 and 0.94, respectively. Good interobserver and intraobserver agreement was shown with regression analysis (F test P value >0.05), the Bland-Altman analysis, and analysis of variance (F test P value >0.95). The mean original SUV was much less than the mean study SUV (P<0.05). The study SUV differed from the SUV of the original report by more than 20% in 50% of the tumors, and by more than 25% in 45% of the tumors. CONCLUSIONS: There was excellent interobserver and intraobserver agreement in SUVs measured in the study environment but poor agreement between study SUVs and those documented in original reports, which can affect treatment decisions substantially.

Bone imaging in metastatic breast cancer.

Bone is the most common site to which breast cancer metastasizes. Imaging-by skeletal scintigraphy, plain radiography, computed tomography, or magnetic resonance imaging-is an essential part, and positron emission tomography or single-photon emission computed tomography have a potential of evaluating bone metastases, but no consensus exists as to the best modality for diagnosing the lesion and for assessing its response to treatment. Imaging bone metastases is problematic because the lesions can be osteolytic, osteoblastic, or mixed, and imaging modalities are based on either direct anatomic visualization of the bone or tumor or indirect measurements of bone or tumor metabolism. Although bone metastases can be treated, their response to treatment is considered "unmeasurable" according to existing response criteria. Therefore, the process by which oncologists and radiologists diagnose and monitor the response of bone metastases needs revision, and the current inability to assess the response of bone metastases excludes patients with breast cancer and bone disease from participating in clinical trials of new treatments for breast cancer. In this review of the MEDLINE literature, we discuss the pros and cons of each modality for diagnosing bone metastases and for assessing their response to treatment and we present a practical approach for diagnosis and assessment of bone metastasis.

The value of 99mTc-sestamibi SPECT/CT over conventional SPECT in the evaluation of parathyroid adenomas or hyperplasia.

UNLABELLED: As SPECT/CT technology evolves, its applications and indications need to be evaluated clinically for more efficient and cost-effective use. This retrospective study evaluated the clinical value of simultaneously acquired (99m)Tc-sestamibi SPECT/CT versus conventional SPECT in diagnosing and locating parathyroid adenomas or hyperplasia in patients with primary hyperparathyroidism. METHODS: Immediately and 60 minutes after intravenous administration of 740-925 MBq of (99m)Tc-sestamibi, static planar images of the neck and chest were obtained. SPECT/CT images were acquired 30 minutes after injection. Two experienced masked readers independently evaluated whether conventional SPECT images provided information beyond what was available from the planar images either by changing the diagnosis or by better locating the glands and whether the SPECT/CT images provided information beyond what was available from the planar plus conventional SPECT images. Forty-eight consecutive patients with a clinical diagnosis of primary hyperparathyroidism were included in the study. The 32 whose scans showed positive results underwent surgical resection and were examined histopathologically. RESULTS: Planar and SPECT imaging, with or without CT fusion, identified 89% of the surgically confirmed diseased parathyroid glands. Use of SPECT/CT changed the diagnosis in only 1 patient (2%) from positive to negative and better located the glands in only 4 patients (8%). SPECT/CT was particularly helpful in locating the 2 ectopic parathyroid adenomas diagnosed in this cohort. Tracer retention in diseased glands did not correlate with histologic characteristics. Also, biochemical markers did not correlate with the scan findings. CONCLUSION: SPECT/CT has no significant clinical value additional to that of conventional SPECT for parathyroid imaging except in locating ectopic parathyroid glands. Eliminating the CT acquisition will spare patients the additional time, radiation exposure, and expense.

Integrated computed tomography-positron emission tomography in patients with potentially resectable malignant pleural mesothelioma: Staging implications.

BACKGROUND: Integrated computed tomography-positron emission tomography imaging with coregistration of anatomic and functional imaging data may improve the accuracy of malignant pleural mesothelioma staging. We evaluate the use of integrated computed tomography-positron emission tomography in patients with malignant pleural mesothelioma who are being considered for extrapleural pneumonectomy. METHODS: Twenty-nine patients with malignant pleural mesothelioma who were judged to be candidates for extrapleural pneumonectomy after clinical and conventional radiologic evaluation underwent whole-body integrated computed tomography-positron emission tomography and pathologic staging. Two reviewers blinded to the results of clinical and pathologic staging retrospectively evaluated computed tomography, positron emission tomography, and coregistered computed tomography-positron emission tomography images. Staging was performed according to the International Mesothelioma Interest Group TNM staging system. Histopathology and/or results of further radiologic evaluation or follow-up served as the reference standard. RESULTS: Integrated computed tomography-positron emission tomography provided additional information in 11 of 29 patients that precluded extrapleural pneumonectomy. The overall tumor stage was correctly classified in 21 of 29 patients. The tumor stage was correctly determined in 15 of 24 patients, 6 of whom had T4 (nonresectable) disease. The node stage was accurately determined in 6 of 17 patients. Extrathoracic metastases not identified by routine clinical and conventional radiologic evaluation were detected in 7 of 29 patients and were found to be diffuse (n = 2) or solitary (n = 5). CONCLUSIONS: Integrated computed tomography-positron emission tomography increases the accuracy of malignant pleural mesothelioma staging and is important in determining the appropriate therapy in patients being considered for extrapleural pneumonectomy.

Lymphomatous involvement of gastrointestinal tract: evaluation by positron emission tomography with (18)F-fluorodeoxyglucose.

AIM: To demonstrate the (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) findings in patients with non-Hodgkinos lymphoma (NHL) involving the gastrointestinal (GI) tract and the clinical utility of modality despite of the known normal uptake of FDG in the GI tract. METHODS: Thirty-three patients with biopsy-proven gastrointestinal NHL who had undergone FDG-PET scan were included. All the patients were injected with 10-15 mCi FDG and scanned approximately 60 min later with a CTI/Siemens HR (+) PET scanner. PET scans were reviewed and the maximum standard uptake value (SUV(max)) of the lesions was measured before and after the treatment, if data were available and compared with histologic diagnoses. RESULTS: Twenty-five patients had a high-grade lymphoma and eight had a low-grade lymphoma. The stomach was the most common site of the involvement (20 patients). In high-grade lymphoma, PET showed focal nodular or diffuse hypermetabolic activity. The average SUV(max)+/-SD was 11.58+/-5.83. After the therapy, the patients whose biopsies showed no evidence of lymphoma had a lower uptake without focal lesions. The SUV(max)+/-SD decreased from 11.58+/-5.83 to 2.21+/-0.78. In patients whose post-treatment biopsies showed lymphoma, the SUV(max)+/-SD was 9.42+/-6.27. Low-grade follicular lymphomas of the colon and stomach showed diffuse hypermetabolic activity in the bowel wall (SUV(max) 8.2 and 10.3, respectively). The SUV(max) was 2.02-3.8 (mean 3.02) in the stomach lesions of patients with MALT lymphoma. ONCLUSION: (18)F-FDG PET contributes to the diagnosis of high-grade gastrointestinal non-Hodgkin's lymphoma, even when there is the normal background FDG activity. Furthermore, the SUV plays a role in evaluating treatment response. Low-grade NHL demonstrates FDG uptake but at a lesser intensity than seen in high-grade NHL.

Diagnostic and therapeutic applications of radiolabeled somatostatin analogs: current status in an oncology center.

From the prospective of a major oncology center in the United States, somatostatin analog radiopeptides currently have limited diagnostic and therapeutic utility. Diagnostic modalities utilitizing Somatostatin Receptor Imaging are now commercially available and the role of this type of method is currently being evaluated. Unlike the unique properties of thyroid tissue facilitating I-131 uptake, targeting of other tissues has required a carrier for the nuclide. Somastostatin peptide analogs have proved attractive based on the ubiquity of distribution and up-regulation in diseased tissue but prospective data is currently scarce. Interest in therapeutic applications of somatostatin analogs as carriers of yttrium, indium and more recently rhenium have resulted in trials with these agents both for endocrine and non-endocrine tumors. At this time, insufficient data exists to justify the indication of "first-line" therapy. The principles of Somatostatin Receptor Imaging and radiotherapy are discussed in this article along with the current status of these modalities in clinical practice as viewed by the author.

Imaging taxane-induced tumor apoptosis using PEGylated, 111In-labeled annexin V.

UNLABELLED: 99mTc-Labeled annexin V has been used for the imaging of tumor apoptosis induced by chemotherapy. However, owing to the short half-life of annexin V, multiple injections of the radiotracer are necessary to capture the peak apoptotic activity. In this study, we evaluated the imaging properties of an (111)In-labeled, long-circulating annexin V. METHODS: Both polyethylene glycol (PEG) and the metal chelator diethylenetriaminepentaacetic acid (DTPA) were simultaneously introduced to annexin V or ovalbumin through the use of a heterofunctional PEG precursor. Imaging studies were performed in mice bearing subcutaneously inoculated human mammary MDA-MB-468 tumors. The mice were treated with poly(L-glutamic acid)-paclitaxel, monoclonal antibody C225, or a combination of poly(L-glutamic acid)-paclitaxel and C225, followed by intravenous injection of (111)In-DTPA-PEG-annexin V. Images were acquired 48 h after the injection of the radiotracer. Autoradiography and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling) staining were performed on adjacent tumor slices for the localization of apoptotic cells. The imaging properties of unPEGylated annexin V and PEGylated ovalbumin were also determined to permit assessment of the specificity of (111)In-DTPA-PEG-annexin V. RESULTS: Tumor apoptotic index increased from 1.67% +/- 0.31% at baseline to 7.60% +/- 0.72% and 11.07% +/- 1.81%, respectively, 4 d after treatment with poly(L-glutamic acid)-paclitaxel or combined poly(L-glutamic acid)-paclitaxel and C225. Tumor uptake (percentage of injected dose per gram of tumor [%ID/g]) of PEGylated (111)In-DTPA-PEG-annexin 4 d after treatment was significantly higher in tumors treated with poly(L-glutamic acid)-paclitaxel (10.76 +/- 1.38 %ID/g; P = 0.001) and with combined poly(L-glutamic acid)-paclitaxel and C225 (9.84 +/- 2.51 %ID/g; P = 0.029) than in nontreated tumors (6.14 +/- 0.67 %ID/g), resulting in enhanced visualization of treated tumors. (111)In-DTPA-PEG-annexin V distributed into the central zone of tumors, whereas (111)In-DTPA-annexin V was largely confined to the tumor periphery. Furthermore, uptake of (111)In-DTPA-PEG-annexin V by tumors correlated with apoptotic index (r = 0.87, P = 0.02). Increase in tumor uptake of the nonspecific PEGylated protein (111)In-DTPA-PEG-ovalbumin was also observed after poly(L-glutamic acid)-paclitaxel treatment (55.6%), although this increase was less than that observed for (111)In-DTPA-PEG-annexin V (96.7%). CONCLUSION: Increased uptake of and improved visualization with (111)In-DTPA-PEG-annexin V in solid tumors after chemotherapy are mediated through both specific binding to apoptotic cells and nonspecific retention of macromolecular contrast agents in the tumors. (111)In-Labeled, PEGylated annexin V may be used to assess tumor response to chemotherapy.

Performance characteristics of a newly developed PET/CT scanner using NEMA standards in 2D and 3D modes.

UNLABELLED: This study evaluates the 2-dimensional (2D) and 3-dimensional (3D) performance characteristics of a newly developed PET/CT scanner using the National Electrical Manufacturers Association (NEMA) NU 2-1994 (NU94) and NEMA NU 2-2001 (NU01) standards. The PET detector array consists of 10,080 individual bismuth germanate crystals arranged in 24 rings of 420 crystals each. The size of each crystal is 6.3 x 6.3 x 30 mm in the axial, transaxial, and radial dimensions, respectively. The PET detector ring diameter is 88.6 cm with axial and transaxial fields of view (FOVs) of 15.7 and 70 cm, respectively. The scanner has a uniform patient port of 70 cm throughout the PET and CT FOV, and the PET scanner is equipped with retractable septa to allow 2D and 3D imaging. METHODS: Spatial resolution, scatter fraction, sensitivity, counting rate, image quality, and accuracy as defined by the NEMA protocols of NU94 and NU01 for 2D and 3D modes are evaluated. The 2D mode data were acquired with a maximum ring difference of 5, whereas the 3D mode acquisition used ring differences of 23. Both 2D and 3D mode data were acquired with an energy window of 375-650 keV. Random estimation from singles counting rate was applied to all relevant analysis. In addition, images from 2 clinical whole-body oncology studies acquired in 2D and 3D modes are shown to demonstrate the image quality obtained from this scanner. RESULTS: The 2D NU94 transaxial resolution is 6.1-mm full width at half maximum (FWHM) 1 cm off center and increases to 6.9 mm tangential and 8.1 mm radial at a radius (R) of 20 cm. NU01 2D average transaxial (axial) FWHM resolution measured 6.1 (5.2) mm at R = 1 cm and 6.7 (6.1) mm at R = 10 cm. The NU94 scatter fraction for 2D (3D) was 13% (29%), whereas the NU01 scatter fraction gave 19% (45%). NU01 peak 2D (3D) noise equivalent counting rate (T(2)/[T + R + S]) was 90.2 (67.8) kilocount per second (kcps) at 52.5 (12) kBq/mL. Total 2D (3D) system sensitivity for true events is 8 (32.9) kcps/kBq/mL for NU94 and 1.95 (9.2) kcps/Bq for NU01. CONCLUSION: The results show excellent system sensitivity with relatively uniform resolution throughout the FOV, making this scanner highly suitable for whole-body studies.

Radiation dosimetry results and safety correlations from 90Y-ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory non-Hodgkin's lymphoma: combined data from 4 clinical trials.

UNLABELLED: Ibritumomab tiuxetan is an anti-CD20 murine IgG1 kappa monoclonal antibody (ibritumomab) conjugated to the linker-chelator tiuxetan, which securely chelates (111)In for imaging or dosimetry and (90)Y for radioimmunotherapy (RIT). Dosimetry and pharmacokinetic data from 4 clinical trials of (90)Y-ibritumomab tiuxetan RIT for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) were combined and assessed for correlations with toxicity data. METHODS: Data from 179 patients were available for analysis. Common eligibility criteria included <25% bone marrow involvement by NHL, no prior myeloablative therapy, and no prior RIT. The baseline platelet count was required to be > or = 100,000 cells/mm(3) for the reduced (90)Y-ibritumomab tiuxetan administered dose (7.4-11 MBq/kg [0.2-0.3 mCi/kg]) or > or = 150,000 cells/mm(3) for the standard (90)Y-ibritumomab tiuxetan administered dose (15 MBq/kg [0.4 mCi/kg]). Patients were given a tracer administered dose of 185 MBq (5 mCi) (111)In-ibritumomab tiuxetan on day 0, evaluated with dosimetry, and then a therapeutic administered dose of 7.4-15 MBq/kg (0.2-0.4 mCi/kg) (90)Y-ibritumomab tiuxetan on day 7. Both ibritumomab tiuxetan administered doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve ibritumomab tiuxetan biodistribution. Residence times for (90)Y in blood and major organs were estimated from (111)In biodistribution, and the MIRDOSE3 computer software program was used, with modifications to account for patient-specific organ masses, to calculate radiation absorbed doses to organs and red marrow. RESULTS: Median radiation absorbed doses for (90)Y were 7.42 Gy to spleen, 4.50 Gy to liver, 2.11 Gy to lung, 0.23 Gy to kidney, 0.62 Gy (blood-derived method) and 0.97 Gy (sacral image-derived method) to red marrow, and 0.57 Gy to total body. The median effective blood half-life was 27 h, and the area under the curve (AUC) was 25 h. No patient failed to meet protocol-defined dosimetry safety criteria and all patients were eligible for treatment. Observed toxicity was primarily hematologic, transient, and reversible. Hematologic toxicity did not correlate with estimates of red marrow radiation absorbed dose, total-body radiation absorbed dose, blood effective half-life, or blood AUC. CONCLUSION: Relapsed or refractory NHL in patients with adequate bone marrow reserve and <25% bone marrow involvement by NHL can be treated safely with (90)Y-ibritumomab tiuxetan RIT on the basis of a fixed, weight-adjusted dosing schedule. Dosimetry and pharmacokinetic results do not correlate with toxicity.

Evaluation of 111In-DTPA-folate as a receptor-targeted diagnostic agent for ovarian cancer: initial clinical results.

UNLABELLED: The cell-membrane folate receptor is a potential molecular target for tumor-selective drug delivery, including radiolabeled folate-chelate conjugates for diagnostic imaging. We report here the initial clinical study of such an agent, (111)In-diethylenetriaminepentaacetic acid (DTPA)-folate, evaluated for diagnosis of ovarian malignancy. METHODS: Thirty-five women were enrolled in a phase I/II clinical study, with 33 completing the surgical follow-up required by the study protocol for definition of disease status. Patients either had a pathologically proven malignancy or were scheduled for surgery for suspected new ovarian cancer (n = 26), recurrent ovarian cancer (n = 5), or endometrial cancer (n = 2). (111)In-DTPA-folate was administered as an intravenous bolus, and whole-body images were obtained at 30 min, 4 h, and (for the first 19 patients) 24 h after injection; SPECT also was done at the delayed imaging times. For 19 of the patients, unlabeled free folic acid was injected before administration of (111)In-DTPA-folate to also assess the impact of folate loading on tracer biodistribution. Masked and unmasked readings of the images by 2 nuclear medicine physicians were compared with the pathologic findings after surgery. RESULTS: Among 33 patients who had surgical intervention, 14 had new or recurrent malignant tumors. All of 7 newly diagnosed ovarian carcinomas were identified by both masked readers (sensitivity, 100%). The sensitivity for detection of 7 recurrent malignancies was 38% for masked readings and 85% for unmasked readings, indicating that correlation with anatomic imaging studies (CT) was highly important in diagnosis of these lesions. Eighteen of the studied patients were found to have benign masses; for this limited population, the specificity of (111)In-DTPA-folate scintigraphy was 76% and 82% for the masked and unmasked analyses, respectively. CONCLUSION: (111)In-DTPA-folate is safe, and possibly effective, for scintigraphy differentiating between malignant and benign ovarian masses.

Radiation dosimetry of 99mTc-labeled C225 in patients with squamous cell carcinoma of the head and neck.

UNLABELLED: This study assessed the radiation dosimetry of 99mTc-labeled ethylene dicysteine (EC) C225 (EC-C225), a promising radioligand for functional tumor imaging. METHODS: Whole-body scanning was performed on 6 patients with head and neck squamous cell carcinoma up to 24 h after administration of 99mTc-EC-C225. Alternate patients who had been randomized to receive C225 in a phase III trial received 99mTc-EC-C225 before their 20-mg test dose or after their 400 mg/m2 loading dose of unlabeled C225 (patients 1/3/5 and 2/4/6, respectively). Radiation dosimetry was assessed using the MIRD method. RESULTS: The critical organ was the kidney, with an average radiation-absorbed dose for all 6 patients of 0.0274 mGy/MBq. The average total-body absorbed dose was 0.0022 mGy/MBq (0.243 cGy/1,110 MBq). CONCLUSION: The new radiopharmaceutical 99mTc-EC-C225 appears to have reasonable dosimetric properties for a diagnostic nuclear medicine agent. Correlation of the imaging results with clinical findings is the next step.