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Biomedical subjects

R L Wahl

Publications and source records attributed to R L Wahl.

At least 19 recordsLinked to original sources
PubMed2001

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.

Adult↗
PubMed2001

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.

Adult↗
PubMed2001

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.

Breast Neoplasms↗
PubMed2001

Detection of atherosclerosis using a novel positron-sensitive probe and 18-fluorodeoxyglucose (FDG).

Inflammation contributes to atherosclerotic plaque remodeling, enlargement and rupture. Non-invasive imaging of coronary artery inflammation could help target therapy to 'vulnerable' atheromata, but is limited because of small tissue mass and arterial motion. Local radiopharmaceutical imaging may overcome some of these limitations. We used a positron-sensitive fiberoptic probe, which can distinguish positron emissions from annihilation photons, to identify diseased from healthy endothelium in an atherosclerotic model. New Zealand White rabbits underwent Fogarty-catheter injury of an iliac artery and then were fed a high-fat diet for 3 weeks. Fasted animals received 90-180 MBq of 18-fluorodeoxyglucose (FDG) 2-4 h before sacrifice and harvest of injured and uninjured iliacs. Arteries were incised longitudinally and the probe was placed in contact with the arterial intima. Multiple measurements were obtained along 1 cm artery segments in 60 s intervals, and corrected for 18F decay and background. Measurements were recorded over 93 injured and normal artery segments in 11 animals. Mean probe Z-scores were 4.8-fold higher (CI 3.4-6.3) over injury atherosclerosis compared with uninjured normal iliac artery segments (P<0.001). Gamma counting confirmed that injured artery segments accumulated more FDG per gram than did normal segments (0.203% x kg injected dose per gram of tissue versus 0.042, P<0.001). Non-arterial tissue also accumulated FDG avidly, particularly reticuloendothelial tissues and blood. Delayed sacrifice, 4 h compared with 2 h after animal FDG injection, further reduced blood background counts and improved the signal-to-noise ratio. Histopathology confirmed that injured iliac artery had significantly higher intimal and medial cross-sectional area compared with uninjured artery. Injured artery also had significantly higher macrophage and smooth muscle cell density. Positron-sensitive probe counts correlated with the intima to media ratio (r =0.63, P = 0.03). Our positron-sensitive probe distinguishes atherosclerotic from healthy artery in a blood-free field. Intravascular study of plaque biology may be feasible using FDG and a positron-sensitive probe.

Animals↗
PubMed2000

Radioimmunotherapy with iodine (131)I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience.

CD20-targeted radioimmunotherapy is a promising new treatment for B-cell non-Hodgkin lymphoma (NHL). We now provide updated and long-term data on 59 chemotherapy-relapsed/refractory patients treated with iodine (131)I tositumomab in a phase I/II single-center study. Fifty-three patients received individualized therapeutic doses, delivering a specified total-body radiation dose (TBD) based on the clearance rate of a preceding dosimetric dose. Six patients received dosimetric doses only. Dose-escalations of TBD were conducted separately in patients who had or had not undergone a prior autologous stem cell transplant (ASCT) until a nonmyeloablative maximally tolerated TBD was established (non-ASCT = 75 cGy, post-ASCT = 45 cGy). Fourteen additional non-ASCT patients were treated with 75 cGy. Unlabeled antibody was given prior to labeled dosimetric and therapeutic doses to improve biodistribution. Forty-two (71%) of 59 patients responded; 20 (34%) had complete responses (CR). Thirty-five (83%) of 42 with low-grade or transformed NHL responded versus 7 (41%) of 17 with de novo intermediate-grade NHL (P =.005). For all 42 responders, the median progression-free survival was 12 months, 20.3 for those with CR. Seven patients remain in CR 3 to 5.7 years. Sixteen patients were re-treated after progression; 9 responded and 5 had a CR. Reversible hematologic toxicity was dose limiting. Only 10 patients (17%) had human anti-mouse antibodies detected. Long-term, 5 patients developed elevated thyroid-stimulating hormone levels, 5 were diagnosed with myelodysplasia and 3 with solid tumors. A single, well-tolerated treatment with iodine (131)I tositumomab can, therefore, produce frequent and durable responses in NHL, especially low-grade or transformed NHL. (Blood. 2000;96:1259-1266)

Adult↗
PubMed2000

Effect of nitroimidazole sensitizers on in vitro glycolytic metabolism of hypoxic squamous cell carcinoma.

Two nitroimidazole compounds, misonidazole (MISO) and nimorazole (NIMO), were evaluated for their potential to modify uptake of [5,6-3H] 2-fluoro-2-deoxy-D-glucose (3H-FDG) in the human squamous carcinoma cell line UT-SCC-5 exposed to increasing levels of hypoxia. UT-SCC-5 cells were incubated with 0-10 mM of MISO or NIMO under normal or reduced oxygen concentrations of 20%, 1.5%, or 0% with 5% CO2 for 6 h, after which 74 KBq of 3H-FDG was added in media for 1 h. In the presence of normal concentrations of O2, both sensitizers increased 3H-FDG uptake by up to 178% (MISO) or 84% (NIMO) when compared with untreated cells. In anoxia, MISO decreased 3H-FDG uptake to 35% of that of control whereas NIMO-treated cells showed a respective decrease in tracer uptake to 62%. Clonogenic assays clearly indicated that MISO was toxic and NIMO moderately toxic for hypoxic cells, whereas both sensitizers exerted only a very modest effect on survival of fully oxygenated cells. Our findings indicate that nitroimidazole treatment consistently increases 3H-FDG uptake into UT-SCC-5 cells under normal oxygen concentrations. In hypoxia, the observed decrease in tracer uptake is dependent on both the level of ambient oxygen and drug concentration and may reflect both direct toxicity and inhibition of glycolysis. The observations may be useful for further applications of 18F-FDG positron emission tomography (PET) to monitor effects of hypoxic cell radiosensitizers on tumor metabolism in vivo.

Carcinoma, Squamous Cell↗
PubMed2000

Tumor-absorbed-dose estimates versus response in tositumomab therapy of previously untreated patients with follicular non-Hodgkin's lymphoma: preliminary report.

I-131-radiolabeled tositumomab (Anti-B1 Antibody), in conjunction with unlabeled tositumomab, was employed in a phase II clinical trial for the therapy of 76 previously-untreated follicular-non-Hodgkin's-lymphoma patients at the University of Michigan Cancer Center. For all patients, conjugate-view images were obtained at six to eight time points on seven consecutive days after a tracer infusion of the antibody. A SPECT image set was obtained on day two or three after the therapy infusion for 57 of the patients. Of these, 55 are suitable for dosimetric evaluation. To date, we have completed analysis and response characterization of 20 patients from the subset of 55. All 20 patients had either a complete response (CR) or a partial response (PR). Conjugate-views provided a time-activity curve for a composite of nearby, individual tumors. These tumors were unresolved in the anterior-posterior projection. Pre-therapy CT provided volume estimates. Therapy radiation dose was computed for the composite tumor by standard MIRD methods. Intra-therapy SPECT allowed the calculation of a separate dose estimate for each individual tumor associated with the composite tumor. Average dose estimates for each patient were also calculated. The 30 individual tumors in PR patients had a mean radiation dose of (369 +/- 54) cGy, while the 56 individual tumors in CR patients had a mean radiation dose of (720 +/- 80) cGy. According to a mixed ANOVA analysis, there was a trend toward a significant difference between the radiation dose absorbed by individual tumors for PR patients and that for CR patients. When the radiation dose depended on only the patient response, the p value was 0.04. When the radiation dose depended on the pre-therapy volume of the individual tumor as well as on the patient response, the p value was 0.06. Since the patient response was complete in 75% of the patients, the analysis of the total cohort of 55 evaluable patients is needed to have a larger number of PR patients to better test the trend toward a significant difference. A pseudo-prediction analysis for patient-level dose and response was also carried out. The positive predictive value and the negative predictive value were 73% and 80%, respectively when a patient's average radiation dose was used. The predictive values were 73% and 60%, respectively, when the patient's average base-10 logarithm of radiation dose was used. A complete overlap for the dose range of CR patients compared to that for PR patients precluded higher predictive values. In conclusion, there was a trend toward a significant difference in the radiation dose between CR and PR patients, but it was only moderately predictive of response.

Antibodies, Monoclonal↗
PubMed2000

Multicenter phase II study of iodine-131 tositumomab for chemotherapy-relapsed/refractory low-grade and transformed low-grade B-cell non-Hodgkin's lymphomas.

PURPOSE: This multicenter phase II study evaluated the efficacy, dosimetry methodology, and safety of iodine-131 tositumomab in patients with chemotherapy-relapsed/refractory low-grade or transformed low-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients received a dosimetric dose that consisted of 450 mg of anti-B1 antibody followed by 35 mg (5 mCi) of iodine-131 tositumomab. Serial total-body gamma counts were then obtained to calculate the patient-specific millicurie activity required to deliver the therapeutic dose. A therapeutic dose of 75 cGy total-body dose (attenuated to 65 cGy in patients with platelet counts of 101,000 to 149,000 cells/mm(3)) was given 7 to 14 days after the dosimetric dose. RESULTS: Forty-five of 47 patients were treated with a single dosimetric and therapeutic dose. Twenty-seven patients (57%) had a response. The response rate was similar in patients with low-grade (57%) or transformed low-grade (60%) NHL. The median duration of response was 9.9 months. Fifteen patients (32%) achieved a complete response (CR; 10 CRs and five clinical CRs), including five patients (50%) with transformed low-grade NHL. The median duration of CR was 19.9 months, and six patients have an ongoing CR. Treatment was well tolerated, with the principal toxicity being hematologic. The most common nonhematologic toxicities that were considered to be possibly related to the treatment included mild to moderate fatigue (32%), nausea (30%), fever (26%), vomiting (15%), infection (13%), pruritus (13%), and rash (13%). Additionally, one patient developed human-antimouse antibodies. CONCLUSION: Iodine-131 tositumomab produced a high overall response rate, and approximately one third of patients had a CR despite having chemotherapy-relapsed or refractory low-grade or transformed low-grade NHL.

Adult↗
PubMed2000

Metabolic response of non-Hodgkin's lymphoma to 131I-anti-B1 radioimmunotherapy: evaluation with FDG PET.

UNLABELLED: 131I-anti-B1 (CD20) radioimmunotherapy (RIT) is a promising approach for treatment of non-Hodgkin's lymphoma (NHL). We assessed the tumor metabolic response to RIT using FDG PET. METHODS: We examined 14 patients with NHL, who were given first a tracer dose of 131I-anti-B1 and then RIT, each preceded by infusion of unlabeled anti-B1. In 8 of 14 patients, PET was performed at baseline and 33-70 d after RIT. The other 6 patients underwent PET at baseline, 6-7 d after the tracer dose, and 5-7 d after RIT to estimate the early response to tracer dose and RIT. To assess tumor FDG uptake, standardized uptake value normalized for lean body mass (SUV-lean) was measured 1 h after FDG injection. RESULTS: After RIT, complete response was observed in 6 patients, partial response in 6, and no response in 2. At 33-70 d after RIT, mean SUV-lean of 6 responders markedly declined to 41% of the baseline value (P < 0.002). Soon after tracer dose and after RIT, mean SUV-lean of the other 6 responders decreased to 79% and 62% of the baseline values, respectively (P < 0.05). In 2 nonresponders, SUV-lean did not significantly decline from the baseline value at 37 d after RIT. CONCLUSION: FDG PET metabolic data obtained 1-2 mo after RIT correlate well with the ultimate best response of NHL to RIT, more significantly than the early data after tracer dose or RIT. FDG uptake in NHL may decline gradually after RIT in responding patients.

Fluorodeoxyglucose F18↗
PubMed2000

Initial results for Hybrid SPECT--conjugate-view tumor dosimetry in 131I-anti-B1 antibody therapy of previously untreated patients with lymphoma.

UNLABELLED: A study of the use of 131I-labeled anti-B1 monoclonal antibody, proceeded by an unlabeled predose, for therapy of previously untreated non-Hodgkin's lymphoma patients has recently been completed at the University of Michigan, Ann Arbor. More than half of the patients treated were imaged intratherapy with SPECT to separate apparently large tumors, unresolved by conjugate views, into individual ones specified by CT scan. The dosimetry of these tumors is reported here. METHODS: The activity-quantification procedure used 3-dimensional CT-to-SPECT fusion so that attenuation maps could be computed from CT and that volumes of interest could be drawn on the CT slices and transferred to the SPECT images. Daily conjugate-view images after a tracer dose of labeled anti-B1 antibody followed by an unlabeled predose provided the shape of the time-activity curve for the calculation of therapy dosimetry. Reconstructed SPECT counts that were within a volume of interest were converted to activity by using a background-and-radius-adaptive conversion factor. Activities were increased for tumors less than 200 g using a recovery-coefficient factor derived from activity measurements for a set of spheres with volumes ranging from 1.6 to 200 cm3. The calculated tumor radiation absorbed dose was based, in part, on the CT volume and on the intratherapy-SPECT activity. RESULTS: The mean of the radiation dose values for 131 abdominal or pelvic tumors in 31 patients was 616 cGy with a standard deviation of +/- 50 cGy. The largest dose was 40 Gy and the smallest dose was 73 cGy. The mean volume for the tumors was 59.2 +/- 11.2 cm3. The correlation coefficient between absorbed dose and tumor volume was small (r2 = 0.007), and the slope of the least-squares fit represented a decrease of only 36.4 cGy per 100 cm3 increase in volume. This small slope may reflect a characteristic of anti-B1 antibody therapy that is important for its success. The mean absorbed dose per unit administered activity was 1.83 +/- 0.145 Gy/GBq. The largest value was 12.6 Gy/GBq, and the smallest value was 0.149 Gy/GBq. The mean dose for 9 axillary tumors in 5 patients was significantly lower than the average dose for abdominal and pelvic tumors (P = 0.01). Therefore, axillary tumors should be grouped separately in assessing dose-response relationships. Anecdotal patient results tended to verify the validity of using the shape of the conjugate-view time-activity curve for the average SPECT-intratherapy curve. However, there was also an indication that the shape varies somewhat for individual tumors with respect to time to peak. CONCLUSION: Hybrid SPECT-conjugate-view dosimetry provided radiation absorbed dose estimates for the individual patient tumors that were resolved by CT.

Adult↗
PubMed2000

Evaluation of the early effect of local irradiation on normal rodent bone marrow metabolism using FDG: preclinical PET studies.

UNLABELLED: Our aim was to evaluate the early effect of local irradiation on normal bone marrow glucose metabolism in rodents, assessed by FDG biodistribution measured by tissue excision and gamma counting. METHODS: Sixty-one rats were divided into nine groups (n = 4-11 per group). Eight groups of rats received either local irradiation (10 Gy) or sham irradiation to the right femur on day 0. Irradiation was performed using a 60Co gamma-ray unit under anesthesia. Each group of rats was fasted overnight and then injected with 5.5-7.4 MBq FDG on day 1, 9, 18, or 30 after the local or sham irradiation. A control group of rats that received neither local nor sham irradiation was studied with FDG on day 0. 18F activity in tissue 1 h after injection was measured using a gamma counter. Smear specimens of bone marrow from bilateral femurs were examined by light microscopy. RESULTS: Tracer uptake was relatively stable in marrow from the sham-irradiated rats. By contrast, FDG uptake of the irradiated marrow on day 1 was significantly higher (mean +/- SD, 0.257 +/- 0.036 percentage injected dose [ID] per gram of tissue per kilogram of rat weight [%ID/g/kg]) than that of the sham group on day 1 (0.187 +/- 0.028 %ID/g/kg) and the control group (0.184 +/- 0.009 %ID/g/kg) (P < 0.05). Tracer uptake in the irradiated marrow on day 9 was significantly lower (0.148 +/- 0.023 %ID/g/kg) than that of the sham group on day 9 (0.193 +/- 0.021 %ID/g/kg) and the control group (P < 0.01). In contrast, the nonirradiated contralateral marrow from irradiated rats showed increased FDG uptake on day 18 (0.274 +/- 0.063 %ID/g/kg) that was significantly higher than that of the sham group on day 18 (0.208 +/- 0.030 %ID/g/kg) and the control group (0.183 +/- 0.018 %ID/g/kg) (P < 0.05). The irradiated marrow smear specimens initially revealed increased percentages of neutrophils on day 1 (45% of 500 nucleoid cells examined per slide) compared with that of the sham group (20%), followed by severely decreased overall cellularity on day 9. CONCLUSION: In this experimental system, normal marrow uptake of FDG transiently rose, then fell, and ultimately returned to baseline after external beam irradiation. Knowledge of this biphasic early irradiation effect on normal bone marrow may be important when the efficacy of radiation therapy on bone metastasis is evaluated using FDG PET after irradiation.

Animals↗
PubMed1999

Capabilities of two- and three-dimensional FDG-PET for detecting small lesions and lymph nodes in the upper torso: a dynamic phantom study.

The capabilities and limitations of two-(2D) and three-dimensional (3D) fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting small tumors and lymph nodes were studied in a phantom modeling the human chest and axilla. Multiple dual-radionuclide phantom studies were performed. Five hollow spheres ranging in diameter from 3 mm to 15 mm were filled with carbon-11 and placed in the axillary and mediastinal regions of an anthropomorphic phantom containing hollow organs filled with 18F to simulate FDG uptake 1 h after injection. Dynamic imaging was performed to acquire PET images with varying target-to-background ratios. Imaging was performed in 2D and 3D acquisition modes, with and without attenuation correction, on a modern PET scanner. Lesion detectability was visually and quantitatively assessed. For objects larger than 9 mm in diameter, target-to-background ratios ranging from approximately 3:1 to approximately 10:1 were detectable. Objects < 9 mm in diameter required a target-to-background ratio of >/=18:1. Target-to-background ratios required for lesion detectability were equivalent for 2D and 3D PET images with and without attenuation correction. In conclusion, 2D and 3D PET with attenuation correction consistently detected "tumors" >/= 9 mm. Lesions < 9 mm could be detected if there was high enough tumor uptake. No statistically significant differences in lesion detection were found for 2D versus 3D PET, or for attenuation-corrected versus non-attenuation-corrected images.

Axilla↗
PubMed1999

Uptake of positron emission tomography tracers in experimental bacterial infections: a comparative biodistribution study of radiolabeled FDG, thymidine, L-methionine, 67Ga-citrate, and 125I-HSA.

The purpose of this study was to evaluate the localization of positron emission tomography (PET) tracers [2-deoxy-2-fluoro-D-glucose (FDG), thymidine, and L-methionine] in sites of bacterial infection, and to contrast this with that of other tracers. The left calf muscles of rats were infected with a suspension of Escherichia coli and the biodistribution of 18F- or 3H-FDG, 3H-thymidine, L-11C- or 3H-methionine, gallium-67 citrate (67Ga-citrate) and iodine-125 human serum albumin (125I-HSA) was determined in these animals. 3H-FDG uptake in the infectious foci was evaluated by autoradiography of histological sections. Although 18F-FDG, 67Ga-citrate, and 125I-HSA showed comparatively high uptake in the infected muscle [the percentage activity of injected dose (ID) per gram of tissue normalized for rat weight in kilogram (%ID/g)xkg at 2 h postinjection was as follows: 18F-FDG, 0.184+/-0.026 to 0.218+/-0.046; 67Ga-citrate, 0.221+/-0.016; 125I-HSA, 0. 198+/-0.019], the infected muscle to blood ratio was much higher for 18F-FDG than for 67Ga-citrate or 125I-HSA (18F-FDG, 10.31+/-0.76 to 14.89+/-2.26; 67Ga-citrate, 1.24+/-0.67; 125I-HSA, 0.20+/-0.02). The draining reactive lymph nodes also showed higher accumulation of 18F-FDG than of 67Ga-citrate or 125I-HSA. The uptake of 3H-thymidine and L-11C- or 3H-methionine in the infected muscle was lower than that of 18F- or 3H-FDG (at 2 h postinjection, 3H-thymidine = 0. 039+/-0.005 and L-3H-methionine = 0.063+/-0.007 (%ID/g)xkg. Autoradiographs showed that the highest 3H-FDG uptake was seen in the area of inflammatory cell infiltration surrounding the necrotic region. In conclusion, 18F-FDG, which rapidly accumulates in sites of bacterial infection and in reactive lymph nodes with a high target to background ratio, appears to be a promising infection detection agent.

Animals↗
PubMed1999

Semi-quantitative ventilation/perfusion scintigraphy and single-photon emission tomography for evaluation of lung volume reduction surgery candidates: description and prediction of clinical outcome.

Ventilation/perfusion scans with single-photon emission tomography (SPET) were reviewed to determine their usefulness in the evaluation of lung volume reduction surgery (LVRS) candidates, and as a predictor of outcome after surgery. Fifty consecutive planar ventilation (99mTc-DTPA aerosol) and perfusion (99mTc-MAA) scans with perfusion SPET of patients evaluated for LVRS were retrospectively reviewed. Technical quality and the severity and extent of radiotracer defects in the upper and lower halves of the lungs were scored from visual inspection of planar scans and SPET data separately. An emphysema index (EI) (extent x severity) for the upper and lower halves of the lung, and an EI ratio for upper to lower lung were calculated for both planar and SPET scans. The ratios were compared with post-LVRS outcomes, 3, 6 and 12 months after surgery. All perfusion and SPET images were technically adequate. Forty-six percent of ventilation scans were not technically adequate due to central airway tracer deposition. Severity, extent, EI scores and EI ratios between perfusion and SPET were in good agreement (r = 0.52-0.68). The mean perfusion EI ratio was significantly different between the 30 patients undergoing biapical LVRS and the 17 patients excluded from LVRS (3.3+/-1.8 versus 1.2+/-0.7; P<0.0001), in keeping with the anatomic distribution of emphysema by which patients were selected for surgery by computed tomography (CT). The perfusion EI ratio correlated moderately with the change in FEV1 at 3 months (r = 0.37, P = 0.04), 6 months (r = 0.36, P = 0.05), and 12 months (r = 0.42, P = 0.03), and the transition dyspnea index at 6 months (r = 0.48, P = 0.014) after LVRS. It is concluded that patients selected to undergo LVRS have more severe and extensive apical perfusion deficits than patients not selected for LVRS, based on CT determination. SPET after aerosol V/Q imaging does not add significantly to planar perfusion scans. Aerosol DTPA ventilation scans are not consistently useful. Perfusion lung scanning may be useful in selecting patients with successful outcomes after LVRS.

Aerosols↗
PubMed1999

Reproducibility of lymphoscintigraphic drainage patterns in sequential 99mTc human serum albumin and 99mTc sulfur colloid studies: implications for sentinel node identification in melanoma.

BACKGROUND: Selective lymphadenectomy, based on prior lymphatic mapping and sentinel node identification and excision, is now the standard management for intermediate-thickness melanomas in many cancer centers worldwide. At our center 99m-labeled technetium human serum albumin (HSA) scans are performed before the day of surgery in some patients with truncal lesions to detect multiple sites of lymphatic drainage. 99mTc sulfur colloid (SC) is then injected before the operation to delineate the sentinel node(s) for gamma-probe-guided excision. Our purpose was to retrospectively evaluate whether comparable diagnostic information resulted from lymphoscintigraphy performed with these 2 different agents. METHODS: All patients with melanoma who had dual sequential 99mTc HSA and 99mTc SC studies between January 1, 1996, and December 31, 1997, were reviewed. RESULTS: Thirty-eight patients underwent paired HSA and SC imaging. Thirty-two patients had concordant scan findings. In all 6 discordant studies, 2 separate drainage areas were defined by HSA, but only 1 drainage area was defined by SC. CONCLUSIONS: In 15.8% of dual studies (6/38 studies), discordant imaging results were obtained between HSA and SC. SC studies alone may result in nonvisualization of at-risk draining lymph node beds and hence failure to identify and excise all sentinel nodes. This could result in inaccurate staging, inappropriate therapy, and altered prognosis. A reduction in SC dose from 3 to 1 mCi was probably the most significant causal factor leading to these discrepancies, which suggests that the 3-mCi dose is preferable.

Adult↗
PubMed1999

Synthesis, in vitro pharmacologic characterization, and preclinical evaluation of N-[2-(1'-piperidinyl)ethyl]-3-[125I]iodo-4-methoxybenzamide (P[125I]MBA) for imaging breast cancer.

The goal of this study was to investigate the potential use of a radioiodinated benzamide, N-[2-(1'-piperidinyl)ethyl]-3-iodo[125I]-4-methoxybenzamide (P[125I]MBA), a sigma receptor binding radioligand for imaging breast cancer. The chemical and radiochemical syntheses of PIMBA are described. The pharmacological evaluation of PIMBA was carried out for sigma-1 and sigma-2 receptor sites. The in vivo pharmacokinetics of the radioiodinated benzamide were determined in rats and comparison of P[125I]MBA with Tc-99m sestamibi were made in a rat mammary tumor model. Sigma-1 affinity (Ki) for PIMBA in guinea pig brain membranes using [3H](+)pentazocine was found to be 11.82 +/- 0.68 nM, whereas sigma-2 affinity in rat liver using [3H]DTG (1,3-o-di-tolylguanidine) was 206 +/- 11 nM. Sites in guinea pig brain membranes labeled by P[125I]MBA showed high affinity for haloperidol, (+)-pentazocine, BD1008, and PIMBA (Ki = 4.87 +/- 1.49, 8.81 +/- 1.97, 0.057 +/- 0.005, 46.9 +/- 1.8 nM, respectively). Competition binding studies were carried out in human ductal breast carcinoma cells (T47D). A dose-dependent inhibition of specific binding was observed with several sigma ligands. Ki values for the inhibition of P[125I]MBA binding in T47D cells for haloperidol, N-[2-(1'-piperidinyl)]ethyl]4-iodobenzamide (IPAB), N-(N-benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP), and PIMBA were found to be 1.30 +/- 0.07, 13 +/- 1.5, 5.19 +/- 2.3, 1.06 +/- 0.5 nM, respectively. The in vitro binding data in guinea pig brain membranes and breast cancer cells confirmed binding to sigma sites. The saturation binding of P[125I]MBA in T47D cells as studied by Scatchard analysis showed saturable binding, with a Kd = 94 +/- 7 nM and a Bmax = 2035 +/- 305 fmol/mg of proteins. Biodistribution studies in Sprague-Dawley rats showed a rapid clearance of P[125I]MBA from the normal organs. The potential of PIMBA in imaging breast cancer was evaluated in Lewis rats bearing syngeneic RMT breast cancers, a cancer that closely mimics human breast cancer histology. At 1 h postinjection, tumor uptake for P[125I]MBA and Tc-99m sestamibi were found to be 0.35 +/- 0.01 and 0.32 +/- 0.01% injected dose/organ (%ID/g), respectively. The %ID/g for liver, kidneys, and heart were 2, 11, and 20 times lower, respectively, for P[125I]MBA as compared with Tc-sestamibi. Slightly higher uptake of P[125I]MBA in tumors (than Tc-sestamibi) and a low nontarget organ uptake warrants further studies of this and other sigma receptor ligands for their use as breast cancer imaging agents.

Animals↗
PubMed1999

Bone marrow cell trafficking following intravenous administration.

To address trafficking of transplanted marrow cells immediately after intravenous infusion, we examined the early fate of infused non-adherent, low-density donor bone marrow cells in a syngeneic mouse model. The presence of infused donor cells, marked with indium-111 oxine (111In), with the fluorescent dye PKH26, or by a detectable transgene marker, was evaluated at 3-48 h in a variety of tissues, including peripheral blood. All three cell-marking methods indicated a rapid (< 4 h) influx of cells into the bone marrow, liver, spleen, muscle and other tissues. Moreover, these tissues remained positive for the 48 h observation period. Interestingly, analysis of PKH26-positive cells in non-myeloablated animals demonstrated that approximately 17% of infused donor marrow cells localized to the marrow space within 15 h, whereas a smaller proportion of donor cells (approximately 1-2%) localized to the marrow in recipients preconditioned by irradiation. In an effort to enrich for cells that specifically home to the bone marrow, PKH26-labelled donor marrow cells were recovered from the first host and infused into a secondary recipient. Although this was a phenotypically undefined population of cells, no increase was observed in the relative fraction of PKH26-labelled cells returning or 'homing' to the marrow of the second recipient. Taken together, these data suggest both that marrow engraftment may be mediated by non-specific 'seeding' rather than a specific homing signal, and that efficient targeting of transplanted cells to the marrow is a complex multifaceted process.

Animals↗