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PubMed2006

In whole blood, LPS, TNF-alpha and GM-CSF increase monocyte uptake of 99mtechnetium stannous colloid but do not affect neutrophil uptake.

INTRODUCTION: (99m)Technetium stannous colloid (TcSnC) is used in white cell scanning. It labels neutrophils and monocytes via phagocytosis, with uptake mediated by the phagocytic receptor CD11b/CD18 in neutrophils. Uptake of TcSnC is altered by gram-negative infection, possibly due to the endotoxin component lipopolysaccharide (LPS) or to cytokines released during infection (e.g., TNF-alpha and IFN-gamma). Endotoxemia and increased TNF-alpha levels also occur in inflammatory bowel disease. Another potential confounder in cell labeling is that sepsis patients may be treated with GM-CSF and G-CSF, which alter phagocytic cell function. This study aimed to determine how these factors affect TcSnC cellular uptake. METHODS: Whole blood from six healthy volunteers was incubated with LPS, TNF-alpha, IFN-gamma, GM-CSF or G-CSF. Samples were then mixed with TcSnC. Blood was separated across density gradients and imaged using a gamma camera. Three radioactive count peaks were observed in each tube: free plasma activity, mononuclear cell uptake and neutrophil uptake. RESULTS: Compared with controls, significant increases in mononuclear cell uptake were induced by LPS, TNF-alpha and GM-CSF stimulation. It was incidentally noted that exogenous estrogens appear to affect TcSnC labeling and may influence the neutrophil response to stimulation. Neutrophil uptake and plasma activity were not significantly affected. IFN-gamma and G-CSF had no significant effect. CONCLUSIONS: In whole blood, the effect of LPS on TcSnC monocyte uptake is different to its effect on neutrophils, consistent with previously reported differences in CD11b/CD18 expression. TNF-alpha response parallels LPS response. GM-CSF also increases TcSnC uptake by monocytes. These effects should be considered when using TcSnC for imaging purposes, as they will tend to increase monocyte labeling. Estrogens may also affect TcSnC labeling. Responses to IFN-gamma and G-CSF are consistent with previously reported effects of these cytokines on CD11b/CD18 expression.

Adult↗
PubMed2006

Advances in the production, processing and microPET image quality of technetium-94m.

This work involves the production, processing and imaging of the short-lived, rarely used positron emission tomography (PET) radionuclide technetium-94m (94mTc). Our procedures are an extension of methods reported in the literature and are detailed within. A key modification was the development of a single step that combines purification and concentration of an aqueous 94mTc-pertechnetate solution, which both reduces processing time and increases the final concentration of the solution. Additionally, a convenient method for the direct recovery of 94mTc into an organic solvent was developed, eliminating the solvent transfer step needed for organic syntheses using 94mTc. Each of these advances potentially extends the scope of syntheses possible with this short-lived radionuclide. To explore the imaging potential of 94mTc, we carried out phantom imaging studies on small-scale high-resolution PET scanners to estimate the limitations of detection associated with 94mTc and PET. Preliminary studies demonstrate that useful images can be obtained with modern image reconstruction algorithms when using a correction for the cascade gamma ray contamination.

Isotope Labeling↗
PubMed2006

Individualized surgery for early gastric cancer guided by sentinel node biopsy.

BACKGROUND: We have reported that lymphatic mapping using indocyanine green (ICG) solution can be a good tool for identifying sentinel nodes (SNs) in gastric cancer. The purpose of this study was to evaluate individualized operations for gastric cancer guided by SN biopsy and to explore the possibility for more limited operative procedures using SN technology. METHODS: SNs were identified by using (99m)Tc-labeled tin colloid and ICG solution in patients with clinically T1N0M0 gastric cancer. When pathologic examination by frozen section revealed metastasis in SNs, we performed a standard D2 gastrectomy. Less extensive lymphadenectomy preserving vagus and pylorus was applied when the SN biopsy was negative. Then, postoperative pathology was analyzed. RESULTS: Among the 80 enrolled patients, 7 patients with apparent node metastasis or T2-3 neoplasms and 10 patients with positive metastasis in SNs underwent D2 gastrectomy. Sixty-one patients with negative metastasis in SNs underwent a less extensive, function-preserving gastrectomy. The false-negative rate in sentinel node biopsy was 23% (3/13) for frozen section and 7% (1/14) for postoperative pathology. In 3 patients with a false-negative result, metastasis was found in lymph nodes located at the station where the tracers were distributed. Of the 7 patients in whom metastasis was detected in 2 or more SNs by frozen section, postoperative pathology revealed that 3 patients (43%) belonged to the N2 category. CONCLUSIONS: SN biopsy is a useful tool for individualizing the operative procedure for early gastric cancer. Dissecting the lymph node stations only where the tracers are distributed may be a promising procedure for patients with no metastatic SNs.

Adult↗
PubMed2006

Lymphatic mapping and sentinel node biopsy in women with high-risk endometrial cancer.

OBJECTIVE: To evaluate fundal injection of blue dye and radiocolloid for lymphatic mapping and sentinel node identification in women with high-risk endometrial cancer. METHODS: At laparotomy, 18 women with high-risk endometrial cancer had isosulfan blue and technitium-99 radiocolloid injected into the uterine fundus subserosally. Sentinel nodes were then identified either by direct observation of blue dye, by radioactive counts using a handheld gamma counter, or by a combination of both methods. The number and location of sentinel node(s) were recorded and compared with the final lymph node specimens after hysterectomy and selective lymphadenectomy. RESULTS: A sentinel node was identified in only 8 (45%) of the cases. Four patients had sentinel nodes only in the pelvis, 2 had sentinel nodes in the pelvis and above the bifurcation of the aorta, and 2 patients had sentinel nodes above the bifurcation of the aorta only. Seven (88%) patients had unilateral drainage of dye and the radiocolloid; the other patient had bilateral drainage. No patients had metastatic disease to sentinel or nonsentinel lymph nodes. CONCLUSIONS: Subserosal fundal injection of blue dye and the radiocolloid is a poor technique for identifying sentinel lymph nodes in patients with high-risk endometrial cancer.

Adult↗
PubMed2007

Sentinel lymph node biopsy improves staging in early cervical cancer.

OBJECTIVES: The main study objective was to describe the distribution of sentinel lymph nodes (SLNs) and the prevalence of SLN micrometastases in patients with early cervical cancer. The secondary objective was to confirm the SLN detection rate and negative predictive value found in our preliminary study. PATIENTS AND METHODS: We prospectively included 25 patients with early cervical cancer, each of whom received an injection of 120 MBq of technetium-99m for preoperative lymphoscintigraphy and intraoperative node detection using an endoscopic gamma probe. Patent blue dye was injected intraoperatively. SLNs were sought in the pelvic and para-aortic drainage areas. Radical iliac dissection was performed routinely at the end of the procedure. SLNs were examined after hematoxylin-eosin-saffron staining; negative specimens were assessed using immunohistochemistry. RESULTS: Most (85%) of the SLNs were in the inter-iliac territory. Para-aortic or parametrial SLNs were found respectively in 2 patients and common iliac SLNs in 5 patients. Thus 9/25 patients had additional information due to SLN detection. One metastasis and one micrometastasis were detected in SLNs. No patients had positive non-sentinel nodes with negative SLNs. CONCLUSION: SLN detection ensures the identification of SLNs in unusual locations in 36% of patients. SLN disease was found in 8% of our patients. Thus, SLN biopsy improves staging in patients with early cervical cancer. Studies in larger patient populations are needed to evaluate the clinical impact of SLN biopsy.

Adenocarcinoma↗
PubMed1983

Implications of lymphoscintigraphy in oncologic practice: principles and differences vis-a-vis other imaging modalities.

The prompt availability of interstitial lymphoscintigraphy and its utilization offer significant advantages over other techniques. Computed tomography represents a highly sensitive technique that suffers from lack of specificity in detecting small lesions. The expense and accessibility of machine time limit its usefulness as a routine survey procedure. Radiographic lymphangiography represents a tedious and difficult process necessitating identification of lymphatic channels for injection of the contrast material for visualization of the lymph nodes in the region being evaluated. With these demonstrated difficulties, the lymph node scanning technique has emerged as a simple, reliable, and reproducible technique for evaluation of multiple lymph node groups.

Antimony↗
PubMed1983

Radiation dose estimates for interstitial radiocolloid lymphoscintigraphy.

The spatial distribution of radioactivity in the injection site, and its rate of clearance, have been measured in patients undergoing various types of interstitial radiocolloid lymphoscintigraphy using 99mTc-antimony sulfide colloid. The clearance of radioactivity from the injection site, and the expansion with time of the localized radioactivity vary considerably for different sites of injection. Maximum absorbed dose estimates of 45.6 rads to the center of the injection site (rectus sheath) and 21 rads to individual lymph nodes have been calculated for patients undergoing internal mammary lymphoscintigraphy with 450 mu Ci injected radioactivity. Absorbed dose estimates for finger web, toe web, and perianal injection sites are also presented.

Antimony↗
PubMed1983

Lymphoscintigraphy--techniques and applications in the management of breast carcinoma.

Radiocolloid lymphoscintigraphy is a versatile, simple technique which has been utilized extensively in the assessment of lymphatic function and structure in anatomic regions accessible to neither clinical examination nor radiocontrast lymphography, as well as in circumstances where radiocontrast lymphography is not feasible. The most important requirement for an effective study are: (a) Determination of the appropriate injection site for reproducibly visualizing the majority of the lymphatics under study and, (b) use of an agent with the optimum properties of a preformed small, uniform, well-dispersed particle colloid. Multiple applications of lymphoscintigraphy in the patient with breast carcinoma have demonstrated its value in distinguishing abnormalities of the internal mammary lymphatics shown to have significant prognostic implications, in providing accurate localization of the parasternal lymphatics for radiation therapy and its potential for determining the status of axillary lymphatics in lieu of surgical intervention. The following review is based on an experience of over 6500 studies in 5550 patients with breast carcinoma.

Antimony↗
PubMed1983

Iliopelvic lymphoscintigraphy.

In patients with genitourinary cancers, it is critically important that lymph node metastases be detected prior to surgery. Information regarding the status of these nodes will influence the type and extent of therapy. Radiologic tests currently available for lymph node imaging--contrast lymphangiography, ultrasound, and computed tomography--are sometimes associated with a high false-negative rate. Iliopelvic lymphoscintigraphy, when performed following bilateral perianal injections of 99mTc-antimony trisulfide colloid, offers a physiologic method for visualizing these nodes and allows demonstration of the internal iliac chain, often not visualized on contrast lymphangiographic studies. Additionally, data from initial patient trials suggest that this technique offers a clinically acceptable level of sensitivity and specificity. This article details the methodology of the technique, and addresses reproducibility, sensitivity, specificity, and image interpretation.

Antimony↗
PubMed1983

Cutaneous lymphoscintigraphy in malignant melanoma.

Melanoma commonly metastasizes to the regional lymph nodes. With early melanomas the accepted therapy is local wide excision and regional lymphadenectomy for nodes in the lymph drainage path. For some melanoma sites the lymph node groups that should be removed are obvious; however, for other sites the decision as to which nodes are at risk may present a difficult problem, since drainage from these sites may vary unpredictably from classical anatomic descriptions. We reviewed recent reports from four institutions using four radiocolloids (colloidal 198gold, 99mtechnetium antimony sulfur colloid (99mTcSbSC), 99mtechnetium sulfur colloid (99mTcSC), and micro 99mtechnetium sulfur colloid (micro 99mTcSC)) to determine lymph shed from melanomas. Correlation with surgical findings was excellent. In addition, drainage to second and third nodal groups, some of which were not clinically predictable, was frequently observed. While all four agents gave good scans, 99mTcSC and micro 99mTcSC are probably the best radiopharmaceuticals.

Antimony↗
PubMed1999

Skeletal metastases from breast cancer: imaging with nuclear medicine.

Breast cancer is a disease that commonly metastasizes to bone, increasing morbidity, mortality, and health service costs. The 99m technetium (99mTc) diphosphonate bone scan historically has played a significant part in the evaluation of skeletal disease and continues to be one of the most clinically utilized investigations in the staging and follow up of breast cancer patients. More tumor-specific radiopharmaceuticals are now being evaluated and, in particular, 18-fluoro-2-deoxyglucose positron emission tomography (18FDG PET) may have a greater role in this disease in the future.

Bone Neoplasms↗
PubMed1997

Effects of nisoldipine and/or enalapril on left ventricular function and exercise capacity in patients with recent anterior myocardial infarction and mild cardiac dysfunction.

Treatment of abnormal remodeling and dysfunction of left ventricle after myocardial infarction is one of the major goals of recent therapeutic interventions. The current study, the Nisoldipine Enalapril Anterior Myocardial infarction Study pilot investigation, was designed to investigate the effects of 12 weeks of treatment with enalapril or nisoldipine or their combination on left ventricular (LV) function and exercise capacity in patients with recent (< 1 month) anterior myocardial infarction and mild LV dysfunction (LV ejection fraction [EF] 38% to 48%). Forty-six patients were studied and received, by random assignment, enalapril (5 mg once per day) plus placebo (n = 14) or nisoldipine (10 mg two times per day) plus placebo (n = 18) or enalapril (5 mg once per day) plus nisoldipine (10 mg two times per day) (n = 14). All patients received aspirin (325 mg) throughout the study. Data on LV EF and peak filling rate at rest and LV EF during exercise were collected during radionuclide ventriculography. In addition, the product of heart rate and systolic blood pressure (rate-pressure product) and exercise time were determined during exercise stress testing. The analyzed parameters were not significantly modified after treatment with enalapril or with nisoldipine. In contrast, the combination of enalapril and nisoldipine significantly raised LV EF at rest (from 43% +/- 3% to 48% +/- 6%, p < 0.01) and during exercise (from 45% +/- 8% to 50% +/- 9%, p < 0.01) and raised peak filling rate at rest (fraction of end-diastolic volume per second) from 1.57 +/- 0.3 to 1.67 +/- 0.3 (p < 0.05). In addition, the combined administration of the two drugs increased the rate-pressure product (values x 10(3)) (from 20.7 +/- 5 to 22.7 +/- 4, p < 0.05) and increased exercise time (from 573 +/- 173 seconds to 668 +/- 178 seconds, p < 0.05). These results show that in patients with recent anterior myocardial infarction and mild LV dysfunction, the combination of the angiotensin-converting enzyme inhibitor enalapril and the dihydropyridine nisoldipine improves resting LV systolic and diastolic function and exercise LV systolic function and exercise capacity.

Adult↗
PubMed1997

Metastatic Ewing cell sarcoma of the sinus and osteoid osteoma of the orbit.

PURPOSE: To familiarize ophthalmologists with the management of a "solitary hot lesion" on bone scan as part of a metastatic examination. METHODS: Case report of a 27-year-old man with primary Ewing sarcoma of the fibula. Bone scan as part of a metastatic evaluation showed increased uptake in the left orbit. A metastatic lesion could not be ruled out radiologically. RESULTS: A biopsy was performed, and the lesion was found to be osteoid osteoma; therefore, the patient received only local radiation therapy to the fibula. Eight months later, the patient developed metastatic Ewing cell sarcoma of the sphenoid sinus and subsequently died. CONCLUSIONS: Because of the high sensitivity but low specificity of bone scan, secondary lesions on bone scan are not necessarily metastases. A biopsy specimen is often required for pathologic diagnosis.

Adult↗
PubMed1995

Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy.

BACKGROUND: The technique of lymphoscintigraphy may allow a more selective approach to the management of clinically negative neck nodes among patients with cutaneous head and neck melanoma. PATIENTS AND METHODS: A group of 97 patients with cutaneous head and neck melanoma had preoperative lymphoscintigraphy using intradermal injections of technetium 99m antimony trisulfide colloid to identify sentinel nodes. Fifty-one patients were eligible for clinical analysis after initial definitive treatment by wide excision only (n = 11), wide excision and elective dissection of the neck (n = 19) or axilla (n = 1), or wide excision and a sentinel node biopsy procedure (n = 20). RESULTS: Sentinel nodes were identified in 95 of 97 lymphoscintigrams, and 85% of patients had multiple sentinel nodes. In 21 patients (22%), sentinel nodes were identified outside the parotid region and the 5 main neck levels, mostly in postauricular nodes (n = 13). Lymphoscintigrams were discordant with clinical predictions in 33 patients (34%). Lymph nodes were positive in 4 elective dissections and 4 sentinel node biopsies. Among 16 patients evaluable after wide excision and a negative sentinel node biopsy, 4 patients subsequently developed metastatic nodes; however, confident identification of all nodes marked as sentinel nodes on lymphoscintigraphy was not achieved at the original biopsy procedure in 3 of these patients. CONCLUSIONS: Lymphoscintigraphy and sentinel node biopsy are more difficult to perform in the head and neck than in other parts of the body. The reliability of sentinel node biopsy based on lymphoscintigraphy may be improved by identifying and marking all nodes that are considered to receive direct lymphatic drainage from the primary melanoma, and by use of a gamma probe intraoperatively.

Adolescent↗
PubMed2000

Gene-modified PA1-STK cells home to tumor sites in patients with malignant pleural mesothelioma.

BACKGROUND: Malignant mesothelioma is an uncommon but lethal cancer of increasing incidence, particularly among patients with a history of exposure to asbestos. Although numerous treatments have been employed, including chemotherapy, radiation therapy, surgical resection, and combinations of the above, no satisfactory treatment yet exists, and affected patients will die of this disease, usually within 12 months. Gene-based therapies constitute a new approach that offers hope of improved control of these tumors while being associated with less morbidity than conventional chemotherapeutic or surgical regimens. We demonstrated that PA1-STK cells home in vivo to mesothelioma deposits, a phenomenon that is required for optimal exertion of this therapeutic concept. METHODS: Gene-modified ovarian cancer cells expressing the thymidine-kinase gene (PA1-STK) were radiolabeled with 99Tc and infused into the pleural space of 4 patients with malignant pleural mesothelioma, then scanned to determine distribution of the cells. RESULTS: PA1-STK cells recognized and adhered preferentially to mesothelioma lining the chest wall. CONCLUSIONS: Cell-based "suicide gene" therapy utilizing the "bystander effect" with the gene-modified ovarian cancer cell line PA1-STK is feasible in human pleural mesothelioma. We have shown that this trafficking and homing of the therapeutic cells to the intrapleural tumor sites, a requirement for success with this novel therapeutic concept, is also valid in humans.

Female↗