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PubMed1989

Reticuloendothelial failure in chronic intra-abdominal sepsis: the role of opsonic fibronectin.

Severe sepsis leads to depression of the reticuloendothelial (RE) system with delayed bloodstream clearance of particulate matter and bacteria. Fibronectin may be an important opsonin of the RE system and low fibronectin levels often accompany severe sepsis in man. We have investigated the effect of prolonged intra-abdominal sepsis on plasma fibronectin concentrations and RE function. Serial plasma fibronectin concentrations were determined in rabbits for 2 weeks after either the induction of sepsis (appendix abscess) (n = 6) or laparotomy only (n = 6). RE function was measured at 2 weeks by determining the clearance kinetics and organ distribution of low dose technetium tin colloid (TTC). There was an early transient depression in plasma fibronectin values followed by elevated concentrations at 48-72 h which were more marked in the sepsis group. There was a delay in the blood clearance with reduced hepatic and increased bone uptake of TTC. We conclude that depletion of opsonic fibronectin is unlikely to be an important factor contributing to the impairment of RE function associated with intra-abdominal sepsis and that RE depression in septic animals is due to intrinsic Kupffer cell dysfunction.

Animals↗
PubMed1989

Medullary carcinoma of the thyroid: management of persistent hypercalcitonaemia utilizing [99mTc] (v) dimercaptosuccinic acid scintigraphy.

Whole body scintigraphy with [99mTc] (v)dimercaptosuccinic acid (pentavalent DMSA) was performed in seven patients with histologically confirmed medullary carcinoma of the thyroid (MCT). Six of these patients had undergone previous thyroid resections for MCT and, although asymptomatic at the time of pentavalent DMSA scintigraphy, had persistent and serial elevations in their plasma calcitonin levels. One additional patient was scanned before and after total thyroidectomy for MCT. The pentavalent DMSA scintigram demonstrated either local neck recurrence (three patients) or distant metastases (two patients) in five of the six asymptomatic patients. In one asymptomatic patient only equivocal neck uptake was demonstrated. Since he had only minimal calcitonin elevations, repeat neck exploration was not performed. The one patient studied before thyroid resection for MCT demonstrated neck uptake before, but not after, total thyroidectomy. The results of the scintigrams had significant impact on patient care and resulted in neck re-exploration (three patients), neck biopsy (one patient), and lumbar spine biopsy and subsequent radiotherapy (one patient). These data demonstrate pentavalent DMSA to be a sensitive localizing agent in the evaluation of asymptomatic MCT patients with hypercalcitonaemia. Accurate targeting of treatment may be shown in due course to have a beneficial impact on survival.

Adult↗
PubMed1990

Effect of acute starvation on plasma fibronectin response to sepsis.

There is evidence that undernutrition may contribute to the reduction in plasma fibronectin concentration and the depression of the reticuloendothelial (RE) system associated with severe sepsis. We have investigated the effects of fasting, surgical trauma and sepsis on plasma fibronectin concentrations and RE function. In experiment 1, plasma fibronectin was measured in rabbits (n = 14) before and 48 h after fasting. In experiment 2, sepsis was induced by devascularization of the appendix in animals on a normal diet (sepsis group, n = 7). A third group of animals underwent only a laparotomy (laparotomy only group, n = 7). Plasma fibronectin concentrations and the blood clearance and organ distribution of 99mtechnetium tin colloid (TTC) were measured 24 h after operation. Compared with pooled reference plasma, fasting in experiment 1 resulted in a reduction in mean(s.e.m.) plasma fibronectin concentration from 98(1.5) per cent to 86(3.7) per cent (T = 2, P less than 0.005). Mean(s.e.m.) plasma fibronectin concentration was raised in the sepsis group to 117(4.6) per cent, compared with 97(2.5) per cent in the laparotomy only group (U = 5, P less than 0.02), but there was no such increase in the fasting and sepsis group. There was a delay in the blood clearance and reduced hepatic uptake of TTC in both sepsis groups. The dissociation between fibronectin concentrations and RE function in animal models of sepsis casts doubt on the importance of fibronectin in RE function.

Acute Disease↗
PubMed2005

Detection of sentinel nodes and micrometastases using radioisotope navigation and immunohistochemistry in patients with gastric cancer.

BACKGROUND: Patients with early gastric cancer may be treated by minimally invasive surgery. This study investigated the value of sentinel node (SN) navigation surgery, including detection of micrometastases, in patients with clinical (c) T1 and T2 gastric cancer. METHODS: The day before surgery (99m)Tc-radiolabelled tin colloid was injected submucosally near the tumour. After resecting the stomach, radioisotope uptake in all dissected lymph nodes was measured during and after surgery. Micrometastasis was detected immunohistochemically using an anticytokeratin antibody. RESULTS: SNs were identified in 99 of 104 patients. The rate of identification of SNs in patients with cT1 and cT2 tumours, excluding three technical failures, was 99 and 95 per cent respectively. Lymph node metastases and/or micrometastases were found in 28 patients (15 cT1 and 13 cT2). In the 15 patients with cT1 tumours, at least one SN contained metastasis and/or micrometastasis. For cT1 tumours, the sensitivity and accuracy of detecting SNs were both 100 per cent. Six patients with cT2 tumours had false-negative results. CONCLUSION: SN navigation surgery appears to be clinically useful only for cT1 tumours. Based on SN results, the extent of lymphadenectomy may be reduced in patients with early gastric cancer.

Adult↗
PubMed2005

Induction of DNA-double-strand breaks by auger electrons from 99mTc complexes with DNA-binding ligands.

The potential of certain Auger electron emitting nuclides for systemic radiotherapeutic applications has recently gained much attention. In particular, the ability of several nuclides, including 111In, 125I, and 123I, to induce DNA double-strand breaks (dsb), a good indicator of cytotoxicity, has been extensively studied. However, this ability has never previously been shown experimentally for 99mTc, which, besides the well-known gamma radiation that is used for diagnostic applications, also emits an average of 1.1 conversion electrons and 4 Auger or Coster-Kronig electrons per decay. Owing to the short range of Auger electrons, the radionuclide needs to be located very close to the DNA for dsb to occur. We synthesized two cationic 99mTcI-tricarbonyl complexes with pendant DNA binders, pyrene and anthraquinone. The X-ray crystal structures of the two complexes could be elucidated. Linear dichroism and UV/Vis spectroscopy revealed that the complex with pyrene intercalates DNA with a stability constant, K, of 1.1 x 10(6) M(-1), while the analogous complex with anthraquinone interacts with DNA in a groove-binding mode and has an affinity value of K=8.9 x 10(4) M(-1). We showed with phiX174 double-stranded DNA that the corresponding 99mTc complexes induce a significant amount of dsb, whereas non-DNA-binding [TcO4]- and nonradioactive Re compounds did not. These results indicate that the Auger electron emitter 99mTc can induce dsb in DNA when decaying in its direct vicinity and this implies potential for systemic radiotherapy with 99mTc complexes.

DNA↗
PubMed2003

N(epsilon) functionalization of metal and organic protected L-histidine for a highly efficient, direct labeling of biomolecules with [Tc(OH2)3(CO)3]+.

Two different pathways for the introduction of an acetyl group at N(epsilon ) in a N(alpha), N(delta), and -COO protected histidine to afford N(epsilon)-(CH(2)COOH)-histidine derivative 7 b are presented. The purpose of this study is the coupling of 7 b to amino groups in bioactive molecules such as peptides. After full deprotection of such a bioconjugate, histidine provides three coordination sites which efficiently coordinate to [(99m)Tc(OH(2))(3)(CO)(3)](+) or [Re(OH(2))(3)(CO)(3)](+) in a facial geometry. This allows the development of novel radiopharmaceuticals. Selective derivatization at the N(epsilon) position has conveniently been achieved by concomitant protection of N(alpha) and N(delta) with a carbonyl group forming a six-membered urea. Cyclic urea ring opening with Fm-OH, coupling of phenylalanine as a model to 7 b through its primary amine and removing of all protecting groups in one step gave a histidine derivative of phenylalanine which could be labeled at 10(-5) M with (99m)Tc in very high yield and even in about 50 % yield at 10(-6) M. The Xray structure of a complex with [Re(CO)(3)](+) in which anilin is coupled to 7 b confirms the facial arrangement of histidine. A second pathway applies directly the [Re(CO)(3)](+) moiety as a protecting group. This is one of the rare examples in which a metal fragment is used as a protecting group for organic functionalities. The coordination to histidine protects the N(alpha), N(delta) and COO group in one single step, subsequent alkylation with BrCH(2)COOH(R) at N(epsilon), coupling to phenylalanine and oxidative deprotection of [Re(CO)(3)](+) to [ReO(4)](-) gave the corresponding bioconjugate in which histidine is coupled to phenylalanine through an acetylamide at N(epsilon). Both methods offer convenient pathways to introduce histidine in a biomolecule under retention of its three coordination sites. The procedures are adaptable to any biomolecule with pendant amines and allow the development of novel radiopharmaceuticals or inversed peptides.

Alkylating Agents↗
PubMed2003

Sentinel lymph nodes with technetium-99m colloidal rhenium sulfide in patients with esophageal carcinoma.

BACKGROUND: The authors assessed the detection of sentinel lymph nodes in patients with esophageal squamous cell carcinoma (SCC) using technetium-99m colloidal rhenium sulfide. They studied whether an analysis of sentinel lymph nodes using cytokeratin (CK) immunohistochemistry increased the accuracy of staging. METHODS: The authors observed 25 patients with thoracic esophageal carcinomas who underwent radical esophagectomy. The day before surgery, technetium-99m colloidal rhenium sulfide was injected into the submucosa at four sites around the primary tumor. Lymphoscintigraphy was performed. Esophagectomy and regional lymph node dissection were performed 17 hours after the technetium-99m injection. After surgery, the resected lymph nodes were evaluated by CK staining. RESULTS: Lymphoscintigraphy detected sentinel lymph nodes in 92% of the patients (23 of 25 patients). The accuracy of sentinel lymph node was 91.3% (21 of 23 patients), the sensitivity was 86.7% (13 of 15 patients), and the false-negative rate was 8.7% (2 of 23 patients). A comparison of the number of sentinel lymph nodes and clinicopathologic factors showed that there was a significant association between the number of sentinel lymph nodes and lymph node status (P < 0.01), pathologic stage (P < 0.05), and the number of metastatic lymph nodes (P < 0.05). Occult metastasis was detected by CK staining in 14 (56%) of the 25 patients and in 23 (1.7%) of 1406 lymph nodes. Because the 2 false-negative (sentinel lymph node-negative and nonsentinel lymph node-positive) patients who had occult metastases in the sentinel lymph nodes, the accuracy of sentinel lymph node evaluation using CK staining was 100% (23 of 23). CONCLUSIONS: Lymphatic mapping with technetium-99m colloidal rhenium sulfide was used to identify the lymphatic basin and was feasible in patients with esophageal SCC. An analysis of sentinel lymph nodes using CK immunohistochemistry increased the accuracy of sentinel lymph node.

Aged↗
PubMed2004

Sentinel lymph node biopsy using periareolar injection of radiocolloid for patients with neoadjuvant chemotherapy-treated breast carcinoma.

BACKGROUND: The feasibility and accuracy of sentinel lymph node (SLN) biopsy after neoadjuvant chemotherapy (NAC) for patients with breast carcinoma have been investigated primarily for the situation in which the radiocolloid imaging agent is injected peritumorally. No such study has involved periareolar injection of radiocolloid, although the usefulness of this injection technique has been demonstrated in patients with early-stage breast carcinoma who have not been treated with NAC. The objective of the current study was to determine the feasibility and accuracy of SLN biopsy using periareolar injection of radiocolloid for patients with breast carcinoma who were treated with NAC. METHODS: Forty-seven patients with AJCC Stage II or III breast carcinoma who were treated with NAC were enrolled in the study. All patients underwent SLN biopsy, which involved a combination of periareolar injection of radiocolloid (technetium 99m tin colloid) and peritumoral injection of isosulfan blue dye, followed by backup axillary lymph node dissection. SLN metastases were examined by hematoxylin and eosin staining and immunohistochemical analysis using an anticytokeratin antibody. RESULTS: An SLN was identified successfully in 44 patients (94%). Twenty-nine patients (66%) had positive SLNs. Fifteen patients had negative SLNs, and 4 patients had positive non-SLNs. Thus, the false-negative rate was 12.1% (4 of 33 patients). The false-negative rate tended to be higher, although not statistically significantly so, among patients who had clinically positive axillary lymph nodes before and/or after NAC (15.8%; 3 of 19 patients) compared with patients who had clinically negative axillary lymph nodes both before and after NAC (7.1%; 1 of 14 patients). CONCLUSIONS: SLN biopsy using periareolar injection of radiocolloid is feasible after NAC. In patients with clinically negative axillary lymph nodes both before and after NAC, SLN biopsy was capable of predicting axillary lymph node status with an accuracy comparable to the accuracy associated with SLN biopsy for patients with early-stage carcinoma who have not been treated with NAC.

Adult↗
PubMed1986

Effect of estrogen/gestagen and 24R,25-dihydroxyvitamin D3 therapy on bone formation in postmenopausal women.

The effect of two different estrogen/gestagen regimens and 24R,25-(OH)2-cholecalciferol on bone formation was studied in a randomized trial with 144 healthy postmenopausal women. Urinary excretion (UE) of 99m-technetium-diphosphonate and serum alkaline phosphatase (AP) was determined before and then once a year for 2 years of treatment. Both estimates of bone formation showed highly significant decreases (p less than .001) to normal premenopausal levels in women receiving unopposed 17 beta-estradiol or in a sequential combination with progestagen, whereas unchanged high values were found in the groups receiving 24R,25-(OH)2D3 and placebo. The data show that bone turnover increases in early postmenopausal women concomitantly with the loss of bone mass, and that hormonal substitutional therapy normalizes the total skeletal turnover as well as preventing bone loss.

24,25-Dihydroxyvitamin D 3↗
PubMed1989

Three-phase [99mTc]diphosphonate scintimetry in septic and nonseptic arthritis of the immature knee: an experimental investigation in dogs.

We compared the informative value of dynamic and static [99mTc]diphosphonate ([99mTc]DPD) scintimetry in early septic arthritis (SA) and chronic nonseptic arthritis (NSA) of the knee in puppies. SA (n = 10), induced by injection of Staphylococcus aureus into one knee, was examined after 48 h. NSA (n = 6) was induced by weekly intraarticular instillation of 1% carrageenan and examined at 2 and 12 weeks. Epiphyseal and metaphyseal count ratios (CRs) between experimental and control joint were calculated in an angiographic phase (0-20 s), a "blood pool" phase (20-256 s), and a bone uptake phase (2 hs). Control dogs (n = 4) had a CR of 1.0 in all regions and phases, the coefficients of variation being 0.06 and 0.03 in dynamic and static phases, respectively. In NSA, all scintimetric phases showed decreased metaphyseal uptake and largely unchanged epiphyseal uptake. Generally, SA exhibited vastly increased angiographic uptake in all regions and increased epiphyseal blood pool uptake, whereas delayed epiphyseal uptake varied and delayed metaphyseal uptake tended to decrease. Two septic joints had generalized reduction in dynamic uptake, probably owing to increased intraarticular pressure; in one of these, dynamic uptake in the distal femoral epiphysis (FE) was totally absent, suggesting temporary circulatory arrest during the dynamic scanning procedure. The use of regional dynamic and static [99mTc]DPD scintimetry increased the pathophysiologic and diagnostic value of joint scintigraphy, especially with respect to the early detection of SA and its avascular complications.

Animals↗
PubMed1991

[99mTc]diphosphonate uptake and hemodynamics in arthritis of the immature dog knee.

The relationship between [99mTc]diphosphonate uptake and bone hemodynamics was studied in canine carrageenan-induced juvenile chronic arthritis. Blood flow was determined with microspheres, plasma and red cell volumes were measured by labeled fibrinogen and red cells, and the microvascular volume and mean transit time of blood were calculated. Normal femoral epiphyses had lower central and higher subchondral blood flow and diphosphonate uptake values. Epiphyseal vascular volume was uniform, resulting in a greater transit time of blood centrally. In arthritis, blood flow and diphosphonate uptake were increased subchondrally and unaffected centrally, while epiphyseal vascular volume was increased throughout, leading to prolonged transit time centrally. The normal metaphyses had low blood flow and diphosphonate uptake values in cancellous bone and very high values in growth plates, but a large vascular volume throughout. The mean transit time therefore was low in growth plates and high in adjacent cancellous bone. Arthritis caused decreased blood flow and diphosphonate uptake in growth plates but increased vascular volume and transit time of blood. Diphosphonate uptake correlated positively with blood flow and plasma volume and negatively with red cell volume in a nonlinear fashion. Thus, changes in diphosphonate uptake and microvascular hemodynamics occur in both epiphyseal and metaphyseal bone in chronic synovitis of the immature knee. The [99mTc]diphosphonate bone scan seems to reflect blood flow, plasma volume, and red cell volume of bone.

Animals↗
PubMed1992

[99mTc]diphosphonate uptake and hemodynamics in experimental arthritis: effect of naproxen in the canine carrageenan injection model.

The impact of naproxen treatment on juxta-articular hemodynamics and bone metabolism in experimental juvenile arthritis was studied in the articular carrageenan injection model. Unilateral gonarthritis was induced for 12 weeks in eight dogs receiving naproxen (dosage, 2 mg/kg) and eight controls. Regional blood flow was assessed by the microsphere method, plasma volume by the distribution space of [125I]fibrinogen, and bone metabolism by the 2-h uptake of [99mTc]diphosphonate ([99mTc]DPD). Synovial effusion was less prominent with naproxen treatment as judged by joint fluid volume and pressure. Naproxen reduced the arthritic capsular hyperemia, almost normalized a severe blood flow increase in patella and both juxta-articular epiphyses, ameliorated an expansion of plasma volume in the patella and the distal femoral epiphysis, and normalized an increased [99mTc]DPD uptake in subchondral femoral bone and the tibial cortex. Significantly increased arteriovenous shunting in the arthritic extremity was unaffected by naproxen. The study suggests that long-term cyclooxygenase inhibition offers protection against hemodynamic and metabolic changes in juxta-articular bone secondary to synovial inflammation.

Animals↗
PubMed1979

Localization of low molecular weight 99mTc-labeled dimercaptodicarboxylic acids in kidney tissue.

Kidney localization of low molecular weight 99mTc-dimercaptodicarboxylic acid complexes was examined in mice. The complexes 99mTc-dimercaptosuccinic acid, 99mTc-dimercaptoglutaric acid, and 99mmTc-dimercaptoadipic acid were formed by reducing sodium 99mTc-pertechnetate with stannous chloride in the presence of 2-10 fold excess ligand at pH 2.5 or 7.5. Kidney specificity decreased as chain length between the mercapto groups increased. Optimum kidney retention occurred with complexes formed at pH 2.5. Complexes prepared at pH 7.5 were rapidly excreted through the urine and feces. Kidney localization of complexes prepared at one pH was not altered if the pH was later changed.

Animals↗
PubMed2003

Intradermal radioisotope injection is superior to subdermal injection for the identification of the sentinel node in breast cancer patients.

BACKGROUND AND OBJECTIVES: The purpose of the present study was to evaluate whether the intradermal injection of radiocolloids would improve the identification rate of sentinel nodes over the subdermal injection in breast cancer patients. METHODS: Sentinel node biopsy was performed in T2 breast cancer patients with clinically negative nodes, using subdermal or intradermal injection of radioisotopes with the peritumoral dye injection. We used Tc-99m tin colloid, with a larger particle size (0.4-5 microm), rather than sulfur colloid and colloidal albumin. RESULTS: The initial 55 patients underwent subdermal injection of radiocolloids; the next 61 patients underwent intradermal injection of radiocolloids for sentinel node biopsy. The detection rate of sentinel nodes was significantly (P = 0.048) higher in the intradermal injection group (61/61, 100%) than in the subdermal injection group (51/55, 92.7%). False-negative rates were comparable between the two groups. Lymphoscintigraphy visualized the sentinel nodes significantly (P < 0.0001) more often in the intradermal injection group (59/61, 96.7%) than in the subdermal injection group (20/54, 37.0%). CONCLUSIONS: A significantly higher identification rate of sentinel node biopsy and lymphoscintigraphy can be achieved by intradermal injection of Tc-99m tin colloid with a large particle size than by subdermal injection.

Axilla↗
PubMed2004

Lymphoscintigraphic and intraoperative detection of the sentinel lymph node in breast cancer patients: the nuclear medicine perspective.

The concept of sentinel lymph node biopsy in breast cancer surgery relates to the fact that the tumor drains in a logical way via the lymphatic system, from the first to upper levels. Therefore, (1) the first lymph node met (the sentinel node) will most likely be the first one affected by metastasis, and (2) a negative sentinel node makes it highly unlikely that other nodes are affected. Sentinel lymph node biopsy would represent a significant advantage as a mini-invasive procedure, considering that, after operation, about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Although the pattern of lymphatic drainage from a breast cancer can be very variable, the mammary gland and the overlying skin can be considered as a biologic unit in which lymphatics tend to follow the vasculature. Considering that tumor lymphatics are disorganized and relatively ineffective, subdermal, and peritumoral injection of small aliquots of radiotracer is preferred to intratumoral administration. (99m)Tc-labeled colloids with most of the particles in the 100-200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy, as images are used to direct the surgeon to the site of the node. The sentinel lymph node should have a significantly higher count than background. After removal of the sentinel node, the axilla must be re-examined to ensure all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in breast cancer surgery is about 94-97% in Institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. At present, there is no definite evidence that a negative sentinel lymph node biopsy is invariably correlated with a negative axillary status, except perhaps for T(1a-b) breast cancers, with size < or =1 cm. Randomized clinical trials should elucidate the impact of avoiding axillary node dissection in patients with a negative sentinel lymph node on the long-term clinical outcome of patients.

Breast Neoplasms↗
PubMed1986

Bone scanning in severe external otitis.

Technetium99 Methylene Diphosphate bone scanning has been considered an early valuable tool to diagnose necrotizing progressive "malignant" external otitis. However, to our knowledge, no formal studies have actually compared bone scans of otherwise young, healthy patients with severe external otitis to scans of patients with clinical presentation of malignant external otitis. Twelve patients with only severe external otitis were studied with Technetium99 Diphosphate and were compared to known cases of malignant otitis. All scans were evaluated by two neuroradiologists with no prior knowledge of the clinical status of the patients. Nine of the 12 patients had positive bone scans with many scans resembling those reported with "malignant" external otitis. Interestingly, there was no consistent correlation between the severity of clinical presentation and the amount of Technetium uptake. These findings suggest that a positive bone scan alone should not be interpreted as indicative of "malignant" external otitis.

Diagnosis, Differential↗