Biomedical subjects

Richard L Wahl

Publications and source records attributed to Richard L Wahl.

At least 19 recordsLinked to original sources

PubMed2007

Therapeutic potential of 90Y- and 131I-labeled anti-CD20 monoclonal antibody in treating non-Hodgkin's lymphoma with pulmonary involvement: a Monte Carlo-based dosimetric analysis.

UNLABELLED: Pulmonary involvement is common in patients with non-Hodgkin's lymphoma (NHL). (90)Y- and (131)I-anti-CD20 antibodies (ibritumomab tiuxetan and tositumomab, respectively) have been approved for the treatment of refractory low-grade follicular NHL. In this work, we used Monte Carlo-based dosimetry to compare the potential of (90)Y and (131)I, based purely on their emission properties, in targeted therapy for NHL lung metastases of various nodule sizes and tumor burdens. METHODS: Lung metastases were simulated as spheres, with radii ranging from 0.2 to 5.0 cm, which were randomly distributed in a voxelized adult male lung phantom. Total tumor burden was varied from 0.2 to 1,641 g. Tumor uptake and retention kinetics of the 2 radionuclides were assumed equivalent; a uniform distribution of activity within tumors was assumed. Absorbed dose to tumors and lung parenchyma per unit activity in lung tumors was calculated by a Monte Carlo-based system using the MCNP4B package. Therapeutic efficacy was defined as the ratio of mean absorbed dose in the tumor to that in normal lung. Dosimetric analysis was also performed for a lung-surface distribution of tumor nodules mimicking pleural metastatic disease. RESULTS: The therapeutic efficacy of both (90)Y and (131)I declined with increasing tumor burden. In treating tumors with radii less than 2.0 cm, (131)I targeting was more efficacious than (90)Y targeting. (90)Y yielded a broader distribution of tumor absorbed doses, with the minimum 54.1% lower than the average dose; for (131)I, the minimum absorbed dose was 33.3% lower than the average. The absorbed dose to normal lungs was reduced when the tumors were distributed on the lung surface. For surface tumors, the reductions in normal-lung absorbed dose were greater for (90)Y than for (131)I, but (131)I continued to provide a greater therapeutic ratio across different tumor burdens and sizes. CONCLUSION: Monte Carlo-based dosimetry was performed to compare the therapeutic potential of (90)Y and (131)I targeting of lung metastases in NHL patients. (131)I provided a therapeutic advantage over (90)Y, especially in tumors with radii less than 2.0 cm and at lower tumor burdens. For both (90)Y- and (131)I-labeled antibodies, treatment is more efficacious when applied to metastatic NHL cases with lower tumor burdens. (131)I has advantages over (90)Y in treating smaller lung metastases.

Adult↗

PubMed2007

Integrating PET and PET/CT into the risk-adapted therapy of lymphoma.

UNLABELLED: Imaging with 18F-FDG PET is increasingly accepted as a valuable tool for lymphoma management. A recent shift in the use of PET and PET/CT in medical practice has become evident. We selected aggressive lymphomas as a platform for the discussion of these imaging modalities in oncology patients and the resulting management questions. METHODS: On the basis of our clinical experience and a review of the literature, we evaluated the emerging role of 18F-FDG PET in staging, response assessment, risk stratification, and tailored therapy. We explored the biologic meaning of true-positive or true-negative PET results in assessing tumor killing and the implications for risk-adapted therapy of lymphoma. RESULTS: PET/CT improves the accuracy of staging and response assessment over that of conventional anatomic imaging. The strong prognostic value of PET for aggressive lymphomas is established, whether the imaging is performed at the end of therapy or after only a few cycles of chemotherapy. How to modify therapy on the basis of PET results is not yet established, although it is clear that high-risk patient subsets can be reliably identified. CONCLUSION: PET/CT improves the accuracy of staging and response assessment over that of CT alone. A negative midtreatment PET result does not indicate the absence of a viable tumor or that therapy can be abbreviated or reduced in intensity. Similarly, a positive PET result does not necessarily indicate a viable tumor or that extending or intensifying treatment will benefit the patient. In assessing response, it is possible that prognosis rests not only on whether the PET result is positive or negative but also on the intensity of the signal. Although the prognostic value of PET for lymphoma is now clear, how to tailor therapy accordingly is a separate matter that requires further investigation.

Fluorodeoxyglucose F18↗

PubMed2006

Preoperative positron emission tomography to evaluate potentially resectable hepatic colorectal metastases.

HYPOTHESIS: Positron emission tomography (PET) influences clinical management in the preoperative evaluation of patients with hepatic metastases from colorectal cancer. DESIGN: Prospective cohort study. SETTING: Academic tertiary care center. PATIENTS: From January 1, 2000, through December 31, 2002, 71 consecutive patients referred with potentially resectable hepatic metastases based on conventional imaging findings underwent PET or PET with computed tomography in the subsequent preoperative evaluation. INTERVENTION: Performance of hepatic resection was based on the results of the overall preoperative evaluation. MAIN OUTCOME MEASURES: Concordance with conventional imaging findings, identification of additional findings, and change in clinical management were analyzed. RESULTS: The PET findings confirmed the lesions identified by conventional imaging techniques in 64 (90%) of the patients. Additional lesions were identified on PET in 23 patients (32%). The information obtained by PET resulted in a change in clinical management in 17 cases (24%). False-positive PET findings occurred in 6 patients (8%), whereas false understaging occurred in 11 (15%). In no cases did PET findings have an adverse impact on patient outcome. CONCLUSIONS: Positron emission tomography provides useful information in the selection of patients with hepatic metastases from colorectal cancer being considered for surgical therapy. Such improved selection may serve to reduce the number of unnecessary surgical explorations and result in improved long-term survival in patients undergoing resection. Positron emission tomography should be integrated into the routine preoperative evaluation of patients being considered for hepatic resection of colorectal metastases.

Adult↗

PubMed2006

Lymphadenopathy resulting from acute hepatitis C infection mimicking metastatic breast carcinoma on FDG PET/CT.

We report a case documenting fluorodeoxyglucose (FDG) accumulation in upper abdominal lymph nodes resulting from acute hepatitis C infection. A 42-year-old African-American female with a history of metastatic breast carcinoma was found to have hypermetabolic porta hepatic, peripancreatic, and paraaortic lymphadenopathy and hypermetabolism in the spleen on a surveillance FDG positron emission tomography/computed tomography (PET/CT) scan. Concurrently, she was diagnosed with acute hepatitis C infection. Antiviral therapy was not recommended secondary to the low level of detectable virus at the time of diagnosis. Her breast cancer therapy regimen was continued unaltered. FDG PET/CT scan was repeated 2 months later as a result of concern that the hypermetabolic lymph nodes represented metastatic disease; however, the scan revealed complete resolution of the previously abnormal findings. The resolution of the lymphadenopathy and the patient's clinical course led to the conclusion that the most likely explanation for the FDG PET/CT findings was inflammation secondary to acute hepatitis C infection and not metastatic breast carcinoma. Inflammatory and infectious processes accumulate FDG, occasionally resulting in false-positives for malignancy. Infected macrophages in the lymph nodes draining the liver in this case and stimulation of a cellular immune response by the hepatitis C virus, with resultant cytokine production by cytotoxic and T-helper cells, offer possible explanations for the findings seen on FDG PET/CT in this case. This case highlights the importance of clinical history and laboratory correlation for the proper interpretation of FDG PET scans.

Abdomen↗

PubMed2006

Stunning and its effect on 3H-FDG uptake and key gene expression in breast cancer cells undergoing chemotherapy.

UNLABELLED: Shortly after chemotherapy, relatively little is known about the expression of key genes and proteins involved in glycolysis. Doxorubicin (DOX) and 5-fluorouracil (5FU) are two commonly used chemotherapy agents that work through differing pathways. Glucose transporter-1 (Glut-1) and hexokinase II (HKII) proteins are highly expressed in many breast carcinomas, but their status while undergoing DOX or 5FU chemotherapy has not been systematically evaluated. METHODS: We evaluated, in vitro, the messenger RNA (mRNA) and protein levels of Glut-1 and HKII in MCF-7, a breast adenocarcinoma cell line, and (3)H-FDG uptake, both in untreated conditions and during treatment with either DOX or 5FU for 24 h. Six time points were evaluated: untreated at time 0; treated for 1 h; treated for 24 h; and 1, 2, and 3 d after chemotherapy. We analyzed tumor cell Glut-1 and HKII mRNA expression with real-time polymerase chain reaction and Western blotting, (3)H-FDG uptake per cell, and cell viability with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. RESULTS: DOX was more effective than 5FU in killing the cancer cells under our study conditions. In untreated MCF-7 cells, the mRNA levels of HKII were typically higher than those of Glut-1, and (3)H-FDG uptake was strongly related to Glut-1 mRNA expression (R(2) = 0.85). Once treated with either drug, (3)H-FDG uptake declined initially, the mRNA ratio was reversed, and Glut-1 mRNA levels were higher than HKII levels. This was verified in the protein assay. With DOX treatment, the cells showed increased Glut-1 mRNA and decreased HKII mRNA for the duration of active treatment; these levels returned to those seen in the untreated cells once the treatment was stopped for 24 h. However, HKII protein levels remained somewhat low. No correlation was seen between (3)H-FDG uptake and HKII mRNA in DOX- and 5FU-treated cells (R(2) = 0.14 and 0.0038, respectively). CONCLUSION: After DOX or 5FU therapy, the relationship between (3)H-FDG uptake and viable cell number can become disjointed, with transient declines in (3)H-FDG uptake in excess of the decline in cell number despite increased Glut-1 mRNA levels. This transient "stunning" has potential implications for (3)H-FDG PET, especially soon after treatment is initiated. However, (3)H-FDG remains a generally valid marker of viable cell number after cancer chemotherapy.

Adenocarcinoma↗

PubMed2006

Iodine biokinetics and dosimetry in radioiodine therapy of thyroid cancer: procedures and results of a prospective international controlled study of ablation after rhTSH or hormone withdrawal.

UNLABELLED: Technical aspects and results of the dosimetric assessments of postoperative radioiodine ablation in the framework of an international, prospective, controlled, randomized, comparative study of the effectiveness of ablation therapy with 3.7 GBq (131)I in differentiated thyroid cancer after stimulation with recombinant human TSH (rhTSH) or by thyroid hormone withdrawal (THW) are presented. METHODS: Sixty-three patients were randomized after thyroidectomy to either the THW or the rhTSH group. Scintigraphic neck images were acquired starting 48 h after radioiodine administration to assess biokinetics in the thyroid remnant. The activity in blood samples was quantified and data from whole-body probe measurements and scintigraphic whole-body scans were combined to deduce retention curves in blood and whole body, respectively. The absorbed dose to the blood was calculated using a modified approach based on the formalism of the MIRD Committee of the Society of Nuclear Medicine. RESULTS: The effective half-time in the remnant thyroid tissue was significantly longer after rhTSH than THW (67.6 +/- 48.8 vs. 48.0 +/- 52.6 h, respectively; P = 0.01), whereas the observed differences of the mean 48-h (131)I uptakes (0.5% +/- 0.7% vs. 0.9% +/- 1.0% after THW; P = 0.1) and residence times (0.9 +/- 1.3 vs. 1.4 +/- 1.5 h after THW; P = 0.1) between the rhTSH and THW groups were not statistically significant. The specific absorbed dose to the blood was significantly (P <0.0001) lower after administration of rhTSH (mean, 0.109 +/- 0.028 mGy/MBq; maximum, 0.18 mGy/MBq) than after THW (mean, 0.167 +/- 0.061 mGy/MBq; maximum, 0.35 mGy/MBq), indicating that higher activities of radioiodine might be safely administered after exogenous stimulation with rhTSH. CONCLUSION: Indication of an influence of the residence time of radioiodine in the blood on the fractional uptake into thyroid remnant was found. A novel regimen is proposed in which therapeutic activities to be administered are determined from the individual specific blood dose.

Adult↗

PubMed2006

In vitro evaluation of adenosine 5'-monophosphate as an imaging agent of tumor metabolism.

UNLABELLED: Adenosine appears to play an important role in tumor growth and metastasis. Synthesized (11)C-adenosine 5'-monophosphate (AMP) has recently been reported as a potential tumor-imaging radiotracer. METHODS: A variety of human tumor cell lines (SKOV-3, SCC-15, U251, U87, Raji, and Daudi) were incubated with 3.7 kBq (0.1 microCi) of [2-(3)H]AMP ((3)H-AMP), [5,6-(3)H]FDG ((3)H-FDG), or [2-(3)H]adenosine ((3)H-adenosine) in low-physiologic-glucose serum-free medium. Selected cells were exposed to caffeine, dipyridamole, adenosine 5'-(alpha,beta-methylene)diphosphate (APCP), or unlabeled adenosine before exposure to the radiotracer. R-phycoerythrin-conjugated mouse antihuman monoclonal antibody to human CD73 was used for immunophenotyping. High-performance liquid chromatography was used to characterize the intracellular metabolites of (3)H-AMP after intracellular uptake. RESULTS: Intracellular uptake of (3)H-AMP was significant-10 to 100 times the uptake of (3)H-FDG, depending on the particular tumor cell line. Preexposure of SKOV-3 cells to caffeine, a competitive inhibitor of adenosine receptors, did not affect cellular uptake of (3)H-AMP. However, preexposure of SKOV-3 cells to dipyridamole, an equilibrative nucleoside transporter inhibitor; APCP, a CD73 (ecto-5'-nucleotidase) inhibitor; or cold adenosine significantly inhibited cellular uptake of (3)H-AMP. SKOV-3 uptake of (3)H-adenosine was inhibited by dipyridamole but not APCP. U251 uptake of (3)H-AMP was significantly inhibited by dipyridamole and APCP. U87 uptake of (3)H-AMP was only partially inhibited by dipyridamole and APCP. However, Raji and Daudi cells had significantly lower uptake of (3)H-AMP than of (3)H-FDG but had significantly increased uptake of (3)H-adenosine, which was inhibited by dipyridamole. Raji and Daudi cells were negative, but the SKOV-3 cells positive, for CD73 cell-surface expression. (3)H-Adenosine metabolites were persistently retained after influx into the cell, predominantly as (3)H-adenosine triphosphate and (3)H-adenosine diphosphate. CONCLUSION: Cancer cell lines evaluated in vitro had significantly elevated uptake of radiolabeled AMP, on the order of 10- to 100-fold, in comparison to radiolabeled FDG. The mechanism of intracellular uptake depends predominantly on equilibrative nucleoside transporters after conversion of AMP to adenosine by CD73 in SKOV-3, SCC-15, and U251 cells. Intracellular retention is due to phosphorylation to adenosine triphosphate and adenosine diphosphate. Raji and Daudi cells have low uptake of radiolabeled AMP because of a lack of CD73 expression. This in vitro evaluation using (3)H-AMP with tumor cell lines supports the potential of (11)C-AMP for use in targeting the nucleoside transport pathway in PET imaging of tumors.

5'-Nucleotidase↗

PubMed2006

Effects of pegfilgrastim on normal biodistribution of 18F-FDG: preclinical and clinical studies.

UNLABELLED: The purpose of this study was to evaluate the effects of pegfilgrastim, a long-acting granulocyte colony-stimulating factor, on the normal biodistribution of (18)F-FDG in an animal model and in humans. METHODS: Two groups of 12 rats received a single subcutaneous injection of either normal saline or pegfilgrastim. One, 7, 14, and 21 d after injection, biodistribution studies were performed 1 h after (18)F-FDG injection. Sixteen breast cancer patients underwent baseline (18)F-FDG PET/CT and, approximately 1 wk after receiving 1 dose of docetaxel and adjunctive pegfilgrastim, follow-up (18)F-FDG PET/CT (scan 2). Standardized uptake values corrected for lean body mass (SUL) were determined for several normal organs before and after therapy. RESULTS: In rats, bone marrow (18)F-FDG uptake (standardized uptake value) was higher in the pegfilgrastim group 1 d after injection (mean +/- SD, 8.3 +/- 4.1 vs. 2.5 +/- 0.2, P < 0.05), whereas (18)F-FDG uptake in blood was lower (0.41 +/- 0.06 vs. 0.49 +/- 0.01, P < 0.05). In patients, mean SUL was higher in bone marrow (4.49 +/- 1.50 vs. 1.33 +/- 0.22, P < 0.0001), spleen (3.29 +/- 0.83 vs. 1.23 +/- 0.23, P < 0.0001), and liver (1.45 +/- 0.25 vs. 1.31 +/- 0.23, P = 0.01) but lower in brain (4.18 +/- 0.76 vs. 5.14 +/- 1.44, P < 0.01) on scan 2 than on the baseline scan. CONCLUSION: In both the animal model and humans, pegfilgrastim markedly increased bone marrow uptake of (18)F-FDG and reduced (18)F-FDG uptake in some normal tissues. These profound alterations in (18)F-FDG biodistribution induced by pegfilgrastim must be considered when one is evaluating quantitative (18)F-FDG PET scans for tumor response to therapy.

Animals↗

PubMed2006

Increased 18F-FDG uptake in degenerative disease of the spine: Characterization with 18F-FDG PET/CT.

UNLABELLED: We determined the prevalence of abnormal spinal 18F-FDG uptake and assessed the relationship between the severity of findings on 18F-FDG PET and the severity of degenerative spinal disease (DSD) on CT. METHODS: PET/CT scans of 150 patients >18 y old, referred for whole-body 18F-FDG PET/CT for evaluation of known or suspected malignancy from June to July 2002, were analyzed retrospectively for the presence of increased 18F-FDG uptake in the spine and for anatomic correlates. Initially, PET images were examined and foci of 18F-FDG uptake in the spine were graded on a 0-4 scale based on intensity of 18F-FDG uptake (0 = definitely normal, 1 = probably normal, 2 = equivocal, 3 = probably abnormal, 4 = definitely abnormal). From PET alone, an impression as to whether lesions were most likely metastases or degenerative, as well the level of the spine involved, was also recorded. CT images of all 150 patients were reviewed independently by a musculoskeletal radiologist, who was unaware of patient identification, history, and findings of other imaging modalities, with the location recorded and severity graded on a 4-point-scale (0 = normal, 1 = mild, 2 = moderate, 3 = severe for both degenerative disk and facet disease). The relationship between PET and CT findings was then determined. RESULTS: Of the 150 patients, 63 (42.0%) had no abnormal findings in the spine on PET (grade 0), 27 (18.0%) had grade 1, 25 (16.7%) had grade 2, 17 (11.3%) had grade 3, and 16 patients (10.7%) had grade 4 18F-FDG uptake for DSD. Two additional patients had apparent spinal metastases with no degenerative changes. Five patients had metastases and DSD (included above). Of the patients who had abnormal spinal findings graded as probable or definite for DSD on CT (grades 3-4), 11 had abnormal findings in the cervical spine, 16 in the thoracic spine, and 23 patients in the lumbosacral spine. Seven patients (4.7%) had PET findings suggestive of spinal metastases. For patients with a maximum regional DSD score of 3, the mean 18F-FDG uptake for that spinal level was 1.4 +/- 1.5, whereas for patients with a maximum regional DSD score of 0, the mean PET grade was significantly lower at 0.4 +/- 0.9 (P = 0.0001). CONCLUSION: Incidental findings on PET suggestive of DSD are common (22% of patients), most common in the lumbosacral spine, and can be recognized on CT. The severity of PET findings correlates with the severity of degenerative disk and facet disease as graded by CT, likely due to the fact that the inflammatory process that accompanies DSD is evident on PET. Increased 18F-FDG uptake in DSD should not be confused with metastatic disease.

Adult↗

PubMed2006

Clinically significant abnormal findings on the "nondiagnostic" CT portion of low-amperage-CT attenuation-corrected myocardial perfusion SPECT/CT studies.

UNLABELLED: Attenuation correction is recommended to optimize the performance of cardiac SPECT. The 2.5-mA CT commonly used for this purpose in myocardial perfusion SPECT is generally considered "nondiagnostic" in quality. In other areas of cardiac and hybrid imaging, diagnostically relevant abnormal findings on higher-quality CT studies have been described. The purpose of this study was to establish the frequency and significance of abnormal findings on low-amperage-CT cardiac SPECT/CT scans and to assess whether a systematic review of the nondiagnostic CT findings should be recommended. METHODS: Two hundred consecutive patients who underwent clinical low-amperage-CT attenuation-corrected myocardial perfusion studies acquired on a SPECT/CT system were included in the study. The cardiac CT images were reviewed in consensus by both an experienced CT reader and a nuclear medicine resident less experienced in CT. Abnormal CT findings of varying significance were recorded. RESULTS: Eighty-one patients had no abnormal CT findings. In the remaining 119 patients, 234 abnormalities were detected. Twenty-five major findings (in 21 patients) were seen, and 16 of these had been previously unrecognized. Sixty-four minor and 131 minimal findings were noted. Fourteen findings were labeled as equivocal (i.e., the CT findings were not definite). CONCLUSION: Potentially significant abnormal findings on the nondiagnostic-CT portion of the cardiac SPECT/CT examination were detected in 10.5% of our patients. These data suggest that, in addition to the review of the emission image dataset, low-amperage-CT findings should routinely be assessed for major diagnostic abnormalities.

Adolescent↗

PubMed2006

Lung toxicity in radioiodine therapy of thyroid carcinoma: development of a dose-rate method and dosimetric implications of the 80-mCi rule.

UNLABELLED: Based on an extensive dataset analyzed by Benua et al., a whole-body retention threshold of 2.96 GBq (80 mCi) at 48 h has been used to limit the radioactivity of (131)I administered to thyroid cancer patients with diffuse pulmonary metastases. In this work, the 80-mCi activity retention limit is used to derive lung-absorbed doses and dose rates. The resulting dose-rate-based limits make it possible to account for patient-specific differences in lung geometry. This is particularly important, for example, in pediatric patients exhibiting diffuse lung metastases. The approach also highlights the impact of altered radioiodine kinetics as seen with recombinant human thyroid-stimulating hormone. METHODS: The dose-rate constraint (DRC) was defined as the absorbed dose rate to the lungs of the adult female reference phantom when 80 mCi of (131)I are in the body and 90% of this is uniformly distributed in the lungs. With this definition, the 80-mCi rule was generalized by calculating the activity required to yield a dose rate equal to DRC using lung-to-lung S factor values corresponding to different reference phantoms. RESULTS: A DRC value of 43.6 cGy/h was obtained. Applying this DRC to the adult male phantom and to the phantom of a 15-y-old yields equivalent 48-h activity limits of 3.72 GBq (101 mCi) and 2.45 GBq (66.2 mCi), respectively. Depending on model parameters, the absorbed doses to lungs ranged from 57 to 112 Gy; the photon-only portion, which better reflects the dose to normal lung parenchyma, ranged from 4.9 to 55 Gy. CONCLUSION: A dose-rate-based version of the 80-mCi rule is derived and used to demonstrate application of this rule to pediatric patients and to adult male patients. The implications of the 80-mCi rule are also examined. The assumption of uniform energy deposition in the lungs leads to substantially overestimated absorbed doses. Severe radiation-induced lung toxicity, expected at normal lung absorbed doses of 25-27 Gy, is avoided, probably because most of the local electron dose is delivered to tumor tissue instead of to normal lung parenchyma. The possibility of using a DRC to adjust treatment for different clinical situations is illustrated. The analysis suggests that a dosimetry-based approach will be particularly important in the treatment of patients with lung metastases when a recombinant human thyroid-stimulating hormone protocol is used.

Computer Simulation↗

PubMed2006

Lung dosimetry for radioiodine treatment planning in the case of diffuse lung metastases.

UNLABELLED: The lungs are the most frequent sites of distant metastasis in differentiated thyroid carcinoma. Radioiodine treatment planning for these patients is usually performed following the Benua-Leeper method, which constrains the administered activity to 2.96 GBq (80 mCi) whole-body retention at 48 h after administration to prevent lung toxicity in the presence of iodine-avid lung metastases. This limit was derived from clinical experience, and a dosimetric analysis of lung and tumor absorbed dose would be useful to understand the implications of this limit on toxicity and tumor control. Because of highly nonuniform lung density and composition as well as the nonuniform activity distribution when the lungs contain tumor nodules, Monte Carlo dosimetry is required to estimate tumor and normal lung absorbed dose. Reassessment of this toxicity limit is also appropriate in light of the contemporary use of recombinant thyrotropin (thyroid-stimulating hormone) (rTSH) to prepare patients for radioiodine therapy. In this work we demonstrated the use of MCNP, a Monte Carlo electron and photon transport code, in a 3-dimensional (3D) imaging-based absorbed dose calculation for tumor and normal lungs. METHODS: A pediatric thyroid cancer patient with diffuse lung metastases was administered 37 MBq of (131)I after preparation with rTSH. SPECT/CT scans were performed over the chest at 27, 74, and 147 h after tracer administration. The time-activity curve for (131)I in the lungs was derived from the whole-body planar imaging and compared with that obtained from the quantitative SPECT methods. Reconstructed and coregistered SPECT/CT images were converted into 3D density and activity probability maps suitable for MCNP4b input. Absorbed dose maps were calculated using electron and photon transport in MCNP4b. Administered activity was estimated on the basis of the maximum tolerated dose (MTD) of 27.25 Gy to the normal lungs. Computational efficiency of the MCNP4b code was studied with a simple segmentation approach. In addition, the Benua-Leeper method was used to estimate the recommended administered activity. The standard dosing plan was modified to account for the weight of this pediatric patient, where the 2.96-GBq (80 mCi) whole-body retention was scaled to 2.44 GBq (66 mCi) to give the same dose rate of 43.6 rad/h in the lungs at 48 h. RESULTS: Using the MCNP4b code, both the spatial dose distribution and a dose-volume histogram were obtained for the lungs. An administered activity of 1.72 GBq (46.4 mCi) delivered the putative MTD of 27.25 Gy to the lungs with a tumor absorbed dose of 63.7 Gy. Directly applying the Benua-Leeper method, an administered activity of 3.89 GBq (105.0 mCi) was obtained, resulting in tumor and lung absorbed doses of 144.2 and 61.6 Gy, respectively, when the MCNP-based dosimetry was applied. The voxel-by-voxel calculation time of 4,642.3 h for photon transport was reduced to 16.8 h when the activity maps were segmented into 20 regions. CONCLUSION: MCNP4b-based, patient-specific 3D dosimetry is feasible and important in the dosimetry of thyroid cancer patients with avid lung metastases that exhibit prolonged retention in the lungs.

Algorithms↗

PubMed2005

Initial experience with FDG-PET/CT in the evaluation of breast cancer.

PURPOSE: We retrospectively reviewed FDG-PET/CT images in patients with breast cancer to determine whether PET/CT improved the level of diagnostic confidence as compared with PET and to compare PET/CT and CT findings at the location of suspected malignancies. METHODS: The study included 75 patients with known breast cancer. The initial PET/CT study for each patient was retrospectively reviewed to determine whether improved diagnostic confidence (IDC) regarding lesion localization and characterization was observed with PET/CT as compared with PET alone. PET/CT and CT findings were compared regarding lesion characterization and staging in 69 of the 75 patients, and in the case of discordant findings, comparison with histological or informative follow-up results was also performed. RESULTS: Fifty of the 75 patients exhibited increased FDG uptake in a total of 95 regions. In the comparison of PET/CT and PET, PET/CT resulted in IDC in 30 (60%) of these 50 patients and in 52 (55%) of the 95 regions. In the comparison between PET/CT and CT in 69 patients, PET/CT demonstrated a significantly better accuracy than CT (P<0.05). PET/CT showed definitely positive findings in 60 regions with malignancies, among which CT exhibited positive findings in 43 (72%). PET/CT and CT accurately staged 59 (86%) and 53 (77%) of the 69 patients, respectively. CONCLUSIONS: PET/CT added incremental diagnostic confidence to PET in more than 50% of patients and regions with increased FDG uptake. PET/CT accurately detected more regions with malignancies than did CT. This initial evaluation suggests that PET/CT is preferable to PET or CT in the diagnosis of breast cancer.

Adult↗

PubMed2005

Re-treatment with I-131 tositumomab in patients with non-Hodgkin's lymphoma who had previously responded to I-131 tositumomab.

PURPOSE: To study efficacy and safety of re-treatment with I-131 tositumomab in patients with low-grade, follicular, or transformed low-grade B-cell lymphoma who relapsed following a response to I-131 tositumomab. PATIENTS AND METHODS: A prior response > or = 3 months to I-131 tositumomab was required. The single therapeutic dose following a dosimetric dose was adjusted to give the same total body dose (in Gy) as that used for the original dose, or was attenuated if the platelet count was less than 150,000 per mm(3) or if the prior treatment resulted in grade 4 cytopenias lasting longer than 7 days. RESULTS: Of 32 patients enrolled, 28 completed the therapeutic dose. A median of four therapies were given before re-treatment. Eighteen (56%) of 32 patients had a complete or partial response (median duration, 15.2 months); eight (25%) had a complete response (median duration, 35 months). Five continue in response from 1.8 to 5.7 years, with a median follow-up of 35 months. The overall median response duration was not significantly different for the two treatments, with no clinical factors predicting response or its duration. Ten of 18 re-responders had longer responses with re-treatment, with five having responses > or = 1.5 years longer. Grade 3/4 neutropenia and thrombocytopenia occurred in 50% and 43% of patients, respectively, similar to initial treatment. Antimouse antibodies developed in 10% of patients, and 12% developed elevated serum thyroid-stimulating hormone. Six patients were diagnosed with second malignancies, including four patients who developed myelodysplastic syndrome (one who had not received the therapeutic dose) and one with acute myelogenous leukemia. CONCLUSION: Re-treatment with I-131 tositumomab following a previous response can produce second responses that can be durable.

Adult↗

PubMed2005

Tositumomab and iodine-131 tositumomab produces durable complete remissions in a subset of heavily pretreated patients with low-grade and transformed non-Hodgkin's lymphomas.

PURPOSE: This study is an integrated efficacy analysis of the five clinical trials of tositumomab and iodine-131 tositumomab in patients with relapsed or refractory low-grade, follicular, or transformed low-grade non-Hodgkin's lymphoma (NHL) that resulted in the regulatory approval of the iodine-131 tositumomab by the US Food and Drug Administration. PATIENTS AND METHODS: This integrated analysis included 250 patients. Patients received a single course of iodine-131 tositumomab. Responses were assessed by an independent panel of radiologists and oncologists. RESULTS: Response rates in the five trials ranged from 47% to 68%; complete response rates ranged from 20% to 38%. With a median follow-up of 5.3 years, the 5-year progression-free survival was 17%. Eighty-one (32%) of 250 patients had a time to progression of > or = 1 year (termed durable response population). For the durable response population, 44% had not progressed at > or = 2.5 to > or = 9.5 years and had a median duration of response of 45.8 months. The median duration of complete response was not reached. The durable response population had many poor prognostic characteristics, including bone marrow involvement (41%), bulky disease > or = 5 cm (49%), and transformed histology (23%). Forty-three percent of the patients had been treated with more than four prior therapies and 36% had not responded to their most recent therapy. CONCLUSION: The tositumomab and iodine-131 tositumomab therapeutic regimen produces high response rates in patients with relapsed or refractory low-grade, follicular, and transformed low-grade NHL, with a sizable subgroup of patients achieving long-term durable responses.

Adult↗

PubMed2005

Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction.

BACKGROUND: Recent results from animal studies suggest that stem cells may be able to home to sites of myocardial injury to assist in tissue regeneration. However, the histological interpretation of postmortem tissue, on which many of these studies are based, has recently been widely debated. METHODS AND RESULTS: With the use of the high sensitivity of a combined single-photon emission CT (SPECT)/CT scanner, the in vivo trafficking of allogeneic mesenchymal stem cells (MSCs) colabeled with a radiotracer and MR contrast agent to acute myocardial infarction was dynamically determined. Redistribution of the labeled MSCs after intravenous injection from initial localization in the lungs to nontarget organs such as the liver, kidney, and spleen was observed within 24 to 48 hours after injection. Focal and diffuse uptake of MSCs in the infarcted myocardium was already visible in SPECT/CT images in the first 24 hours after injection and persisted until 7 days after injection and was validated by tissue counts of radioactivity. In contrast, MRI was unable to demonstrate targeted cardiac localization of MSCs in part because of the lower sensitivity of MRI. CONCLUSIONS: Noninvasive radionuclide imaging is well suited to dynamically track the biodistribution and trafficking of mesenchymal stem cells to both target and nontarget organs.

Animals↗

PubMed2005

Combined PET/CT for detecting recurrent ovarian cancer limited to retroperitoneal lymph nodes.

OBJECTIVE: To evaluate the utility of combined positron emission tomography/computed tomography (PET/CT) for detecting recurrent epithelial ovarian cancer limited to retroperitoneal adenopathy. METHODS: Fourteen patients (median age = 53 years) with rising serum CA125 levels, and negative or equivocal conventional CT imaging > or = 6 months after primary therapy were retrospectively identified as having recurrent disease limited to retroperitoneal lymph nodes by combined PET/CT and underwent surgical reassessment of targeted nodal basins. Fisher's Exact Test was used to measure the ability of PET/CT to predict isolated retroperitoneal nodal disease. RESULTS: The median increase in serum CA125 from baseline nadir was 14 U/ml (range = 2-76 U/ml). There were 29 target nodes in 15 nodal basins identified with increased metabolic uptake on combined PET/CT. Eleven patients (78.6%) had recurrent ovarian cancer in retroperitoneal lymph nodes targeted by PET/CT. Of 143 nodes retrieved, 59 contained recurrent ovarian cancer (median nodal diameter = 2.5 cm, range = 0.8-5.2 cm). For all target nodal basins, the sensitivity, specificity, positive and negative predictive values, and accuracy for recurrent ovarian cancer in dissected lymph nodes were: 40.7% (24/59), 94.0% (79/84), 82.8% (24/29), 69.3% (79/114), and 72.0% (103/143) (P < 0.001). PET/CT failed to identify microscopic disease in 59.3% of pathologically positive nodes. CONCLUSION: Combined PET/CT demonstrates high positive predictive value in identifying recurrent ovarian cancer in retroperitoneal lymph nodes when conventional CT findings are negative or equivocal. The high incidence of occult disease within the target nodal basins suggests that regional lymphadenectomy may be necessary for complete secondary cytoreduction of recurrent disease.

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PubMed2005

131I-tositumomab therapy as initial treatment for follicular lymphoma.

BACKGROUND: Advanced-stage follicular B-cell lymphoma is considered incurable. Anti-CD20 radioimmunotherapy is effective in patients who have had a relapse after chemotherapy or who have refractory follicular lymphoma, but it has not been tested in previously untreated patients. METHODS: Seventy-six patients with stage III or IV follicular lymphoma received as initial therapy a single course of treatment with 131I-tositumomab therapy (registered as Tositumomab and Iodine I 131 Tositumomab [the Bexxar therapeutic regimen]). This consisted of a dosimetric dose of tositumomab and 131I-labeled tositumomab followed one week later by a therapeutic dose, delivering 75 cGy of radiation to the total body. RESULTS: Ninety-five percent of the patients had any response, and 75 percent had a complete response. The use of polymerase chain reaction (PCR) to detect rearrangement of the BCL2 gene showed molecular responses in 80 percent of assessable patients who had a clinical complete response. After a median follow-up of 5.1 years, the actuarial 5-year progression-free survival for all patients was 59 percent, with a median progression-free survival of 6.1 years. The annualized rate of relapse progressively decreased over time: 25 percent, 13 percent, and 12 percent during the first, second, and third years, respectively, and 4.4 percent per year after three years. Of 57 patients who had a complete response, 40 remained in remission for 4.3 to 7.7 years. Hematologic toxicity was moderate, with no patient requiring transfusions or hematopoietic growth factors. No cases of myelodysplastic syndrome have been observed. CONCLUSIONS: A single one-week course of 131I-tositumomab therapy as initial treatment can induce prolonged clinical and molecular remissions in patients with advanced follicular lymphoma.

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