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Synthesis and characterization of technetium-99m-labeled tropanes as dopamine transporter-imaging agents.

In the development of novel Tc-99m-labeled tropane derivatives as dopamine transporter (reuptake site)-imaging agents, a series of neutral and lipophilic complexes containing bis-(aminoethanethiol) as a neutral complexing moiety for a [99mTc]TcO3+ center core was successfully prepared. Biological evaluation of the Tc-99m-labeled complexes 13-16 as central nervous system (CNS) dopamine transporter-imaging agents was reported. Synthesis of the tropane derivatives was achieved by stepwise reactions adding two aminoethanethiol units. The final free thiol ligands were obtained by deblocking the 4-methoxybenzyl protecting group with Hg(OAc)2 to obtain trifluoroacetate salts. All of the Tc-99m complexes, with the exception of 16, displayed good initial brain uptake and selective uptake in the striatal area, where dopamine transporters are concentrated. One of the compounds, [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo [3.2.1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethy] amino]ethanethiolato-(3-)-N2,N2',S2,S2'] oxo-[1R-(exo-exo)]- [99mTc]technetium,[99mTc]TRODAT-1 (13), displayed the highest initial uptake in rat brain (0.4% at 2 min post iv injection); the striatal/cerebellar (ST/ CB) ratio reached 2.8 at 60 min after an iv injection. The specific uptake in rat brain can be blocked by pretreating rats with a competing dopamine transporter binding agent, beta-CIT (RTI-55, 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane; iv, 1 mg/kg), which reduced the regional brain uptake ratio (ST/CB) to 1.2. In contrast, the specific striatal uptake was not affected by pretreating rats with a noncompeting ligand, haldol (iv, 1 mg/kg). After an iv injection of 9 mCi of [99mTc]TRODAT-1 (13), in vivo images of baboon brain using single-photon emission-computed tomography exhibited excellent localization in striatum (basal ganglia), where dopamine neurons are known to be concentrated. This series of compounds may provide a convenient source of short-lived imaging agents for routine diagnosis of CNS diseases (i.e., Parkinson's disease) in which changes in the dopamine transporter concentration are implicated.

Animals↗

Implementation of technetium-99m MIBI SPECT imaging guidelines: optimizing the two day stress-rest protocol.

OBJECTIVES: In a previous study in 460 patients, we found that in patients with suspected or known coronary artery disease undergoing stress-rest technetium-99m sestamibi (MIBI) SPECT myocardial perfusion imaging, rest SPECT imaging could be withhold in approximately 20% of patients because of a completely normal stress study. The present study was set up to evaluate the consequences of the implementation of this finding in a subsequent population of patients, and to set standards for the variety of protocols now used for MIBI SPECT imaging. METHODS: Within a period of 4 months, 235 consecutive patients referred for MIBI SPECT scintigraphy were studied. All patients had stable cardiac chest pain and underwent symptom-limited exercise MIBI SPECT perfusion imaging. The stress SPECT images were reconstructed and evaluated immediately after acquisition of the images. In case of a clearly normal stress SPECT study, rest imaging was cancelled. RESULTS: Twenty-six of 235 patients (11%) had a completely normal stress MIBI SPECT study and the rest SPECT imaging procedure could be subsequently cancelled. In 20 patients (9%) the stress SPECT was inconclusive, and in 189 (80%) of patients stress imaging was clearly abnormal. In the first month of the study, the nuclear medicine physicians and cardiologists would interprete only 6% of the stress images as normal, while this number increased to 13% after 9 weeks, with a mean of 11% for the whole investigation period of 4 months. CONCLUSION: In patients undergoing stress MIBI SPECT imaging, it was found justified to cancel rest MIBI SPECT imaging in at least 11% of patients because of a completely normal stress SPECT. As 9% of the images were inconclusive, the number of normal stress images could theoretically increase to 20% if reliable measures are taken to improve reading accuracy. This number is in close agreement with the number of normal stress studies previously reported by our institution and would lead to a considerable reduction of radiation dose, costs, and increased convenience for an important subset of patients.

Adolescent↗

Technetium-99m methoxyisobutylisonitrile chest imaging for small-cell lung cancer. Relationship to chemotherapy response (six courses of combination of cisplatin and etoposide) and p-glycoprotein or multidrug resistance related protein expression.

AIMS: This is a retrospective and adaptive randomization study. The purpose of this study was to evaluate the relationship between technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) chest-imaging results, chemotherapy response and P-glycoprotein (Pgp) or multidrug resistance related protein (MRP) expression in small-cell lung cancer (SCLC). PATIENTS AND METHODS: Before chemotherapy, 30 patients (11 females, 19 males, ages: 52-69 years) with SCLC, including 14 extensive diseases without localized problems and 16 limited diseases in excess of solitary pulmonary nodule, underwent early chest imaging, including visual interpretation and quantitative analyses of tumor uptake ratio (TUR), 10 minutes after intravenous injection of Tc-99m MIBI. Immunohistochemical analyses were performed, using multiple nonconsecutive sections of the biopsy specimens, to detect Pgp and MRP expressions. Chemotherapy response was evaluated in the third month after completion of treatment by clinical and radiological methods. RESULTS: All 15 (100%) of the SCLC patients with complete or partial response had positive Tc-99m MIBI chest SPECT results, but negative ones for both Pgp and MRP expression. Twelve of the 15 (80%) SCLC patients with no response or progressive disease had negative Tc-99m MIBI chest SPECT results and were positive for either Pgp or MRP expression (P < 0.05). Negative Tc-99m MIBI chest SPECT results predicted complete or partial response. The TUR of patients with complete or partial response (1.91 +/- 0.29 with a 95% confidence interval (95% CI): 1.75-2.07) was significantly higher than that of patients with no response or progressive disease (1.19 +/- 0.28 with a 95% CI: 1.04-1.35). CONCLUSION: Tc-99m MIBI chest images are a potential tool for understanding Pgp and MRP expressions in SCLC and for predicting patient chemotherapy response.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Relationship between exercise-induced ST segmental depression and myocardial ischemia assessed by technetium-99m tetrofosmin SPECT imaging in patients with inferior Q wave myocardial infarction.

BACKGROUND: ST segment depression (STD) is a standard electrocardiographic sign of myocardial ischemia. Although STD may represent reciprocal changes in patients with previous myocardial infarction, studies of reciprocal changes during exercise testing are scarce. METHODS: From December 1999 to December 2000, 160 patients (119 males, 41 females, mean age 54 +/- 8 years), undergoing, maximal or symptom-limited exercise treadmill test (Bruce-protocol), myocardial perfusion scintigraphy using technetium-99m tetrofosmin single photon emission computed tomography (SPECT) imaging, within 30 days of an uncomplicated inferior Q wave myocardial infarction. The location of STD at the electrocardiogram (ECG) was defined as anterior (V1-4), high lateral (I, aVL), and lateral (V5-6). Ischemia was defined as reversible perfusion abnormalities. RESULTS: STD occurred in anterior leads in 29 patients (18.1%), in the lateral leads in 41 patients (25.6%), in the high lateral leads in 20 patients (12.5%). In 70 patients (43.8%) no significant STD occurred during the exercise test. ST segment elevation occurred in 28 patients (17.5%) in inferior leads. High lateral STD was associated with inferior ST elevation in 16 patients (80%), whereas only eight patients (19.5%) with lateral STD and nine patients (31%) with anterior STD were associated with inferior ST elevation. Ischemia was detected in 63 of 90 patients (70%) with and in 10 of 70 patients (14.3%) without STD (p < 0.0001). Patients with high lateral STD had a higher prevalence of fixed perfusion defects in the inferior wall (95 vs. 27.8%) and in posterolateral wall (75 vs. 18.9%) compared with other patients (p = 0.003 and 0.002, respectively). Ischemia was more prevalent in patients with lateral STD than without (87.8 vs. 14.3%, p < 0.0001). CONCLUSION: In patients with inferior Q wave, the presence of exercise-induced STD in lateral and anterior leads appears to be a sign of myocardial ischemia, and may require invasive evaluation; on the other hand, the presence of STD in high lateral leads should be recognized as a reciprocal change for ST elevation in the inferior leads, and may not be an indication for invasive evaluation.

Electrocardiography↗

Discordance between dipyridamole technetium-99m-sestamibi myocardial perfusion single photon emission computed tomography and two-dimensional echocardiography in Kawasaki disease--a preliminary report.

This study attempts to establish a noninvasive diagnostic method for early assessment of cardiac involvement in Kawasaki disease (KD), 36 children with KD were studied. The presence of abnormal coronary arteries (CA) with aneurysms was determined by experienced pediatric cardiologists using two-dimensional echocardiography (2D-Echo). Rest and dipyridamole-stress technetium-99m sestamibi (Tc-MIBI) single photon emission computed tomography (SPECT) was performed on the 36 children with KD for the assessment of myocardial perfusion and for comparison with 2D-Echo findings. The results showed that (1) 17/36 (47.2%) of the cases had no aneurysm and 19/36 (52.8%) had significant aneurysms; (2) 16/36 (44.4%) of the cases had normal myocardial perfusion and 20/36 (55.6%) had myocardial perfusion defects; (3) 9/36 (25.0%) cases showed both normal 2D-Echo and Tc-MIBI SPECT findings and 12/36 (33.3%) showed both abnormal 2D-Echo and Tc-MIBI SPECT findings; and (4) There was poor agreement between 2D-Echo and Tc-MIBI SPECT findings (kappa-value = 0.161, p = 0.332). We concluded that the most of the KD children had aneurysms or abnormal myocardial perfusion. However, poor agreement exists between 2D-Echo and Tc-MIBI SPECT findings with aneurysms and abnormal myocardial perfusion in patients with KD.

Adolescent↗

Evaluation of the phytic acid effect on the labeling of blood elements with technetium-99m and on the survival of a strain of Escherichia coli treated with stannous fluoride.

The labeling of red blood cells with technetium-99m (99mTc) depends on a reducing agent and stannous ions, as chloride or fluoride, are widely utilized. This labeling may also be altered by drugs. Moreover, some authors have reported that the survival of Escherichia coli (E. coli) cultures decreases in presence of stannous ions. Phytic acid is present in the daily diet and we evaluated its influence on: (i) the labeling of blood elements with 99mTc and (ii) on the survival of an E. coli strain treated with stannous fluoride. Heparinized whole blood was withdrawn from Wistar rats and it was incubated with stannous chloride and with 99mTc, as sodium pertechnetate, centrifuged and plasma (P) and blood cells (BC) were isolated. Samples of P and BC were also precipitated with trichloroacetic acid, centrifuged and soluble (SF) and insoluble fractions (IF) isolated. E. coli culture was treated with stannous fluoride in presence of phytic acid. As phytic acid altered the fixation of 99mTc on BC, on IF-P and on IF-BC and, moreover, it abolished the lethal effect of stannous fluoride on the E. coli culture, we can suggest that, probably, phytic acid would have chelating properties to the stannous ions.

Animals↗

Radioimmunoscintigraphy of intracranial glioma xenograft with a technetium-99m-labeled mouse monoclonal antibody specifically recognizing type III mutant epidermal growth factor receptor.

The type III mutant epidermal growth factor receptor (EGFR) is expressed on the cell surface of a subset of glioma, but not of normal tissues. In this study, we investigated the in vivo kinetics of 3C10 mouse monoclonal antibody (mAb), specifically recognizing the type III mutant EGFR (EGFRvIII), using athymic nude mice bearing the intracranial glioma xenograft overexpressing the EGFRvIII. Human glioma cell line, U87MG, expressing the wild type EGFR and the transfectant, named U87MG x deltaEGFR, expressing the EGFRvIII, were transplanted subcutaneously or intracranially to nude mice. 3C10 mAb labeled with a technetium-99m (99mTc) was intravenously injected into these nude mice and then the mice were sacrificed at 24 h later, and the 99mTc-uptake by xenografts and major normal organs was measured to determine the biodistribution of mAb. Furthermore, at 3, 6 and 24 h after injection of 99mTc-labeled 3C10 mAb, whole-body scintigraphy was obtained with a gamma camera to localize the tumor site. 3C10 mAb significantly accumulated to U87MG x deltaEGFR xenografts transplanted subcutaneously or intracranially in nude mice, showing high tumor-to-blood ratio of 10.30 and 4.01, respectively. In contrast, uptake of control antibody in the intracranial tumor was as low as 0.43. In scintigrams, intracranially transplanted U87MG x deltaEGFR xenografts were detectable at 3 h after injection of 99mTc-labeled 3C10 mAb. These results suggest that intravenously injected 3C10 mAb specifically accumulated to the subcutaneous or intracranial glioma xenograft expressing the EGFRvIII and 3C10 mAb is a potential diagnostic and therapeutic agent for patients with gliomas expressing the EGFRvIII.

Animals↗

Technetium-99m-Labeled N-(2-hydroxypropyl) methacrylamide copolymers: synthesis, characterization, and in vivo biodistribution.

PURPOSE: To synthesize novel technetium-99m (99mTc)-labeled N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers and characterize the effect of charge and molecular weight on their biodistribution in SCID mice. METHODS: Electronegative and neutral 7-kDa, 21-kDa, and 70-kDa HPMA copolymers containing a 99mTc chelating comonomer, bearing N-omega-bis(2-pyridylmethyl)-L-lysine (DPK), were synthesized by free-radical precipitation copolymerization. The copolymers were labeled via 99mTc tricarbonyl chelation to DPK-bearing comonomer. They were characterized by side-chain content, molecular weight, molecular weight distribution, radiochemical purity, and labeling stability. Scintigraphic images were obtained during the first 90 min and at 24 h postintravenous injection in SCID mice. At 24 h, organ radioactivity was determined from necropsy tissue counting. RESULTS: 99mTc-labeled HPMA copolymers showed greater than 90% stability over a 24-h challenge with cysteine and histidine. Scintigraphic images and the necropsy data showed that the negatively charged copolymers were eliminated from the body significantly faster than the neutral copolymers in a size-dependent manner. CONCLUSIONS: To facilitate clinical scintigraphic imaging, stable chelation of 99mTc may be achieved by incorporation of a DPK-bearing comonomer into the HPMA backbone. Electronegative and neutral 99mTc-labeled HPMA copolymers of 7, 21, and 70 kDa show significant variation in organ biodistribution in SCID mice. 99mTc-labeled HPMA copolymers could be used as diagnostic agents and to study pharmacokinetics of delivery systems based on these copolymers.

Acrylamides↗

Stable one-step technetium-99m labeling of His-tagged recombinant proteins with a novel Tc(I)-carbonyl complex.

We have developed a technetium labeling technology based on a new organometallic chemistry, which involves simple mixing of the novel reagent, a 99m Tc(I)-carbonyl compound, with a His-tagged recombinant protein. This method obviates the labeling of unpaired engineered cysteines, which frequently create problems in large-scale expression and storage of disulfide-containing proteins. In this study, we labeled antibody single-chain Fv fragments to high specific activities (90 mCi/mg), and the label was very stable to serum and all other challenges tested. The pharmacokinetic characteristics were indistinguishable from iodinated scFv fragments, and thus scFV fragments labeled by the new method will be suitable for biodistribution studies. This novel labeling method should be applicable not only to diagnostic imaging with 99mTc, but also to radioimmunotherapy approaches with 186/188 Re, and its use can be easily extended to almost any recombinant protein or synthetic peptide.

Aldehydes↗

Evaluation of thrombus detection in a rabbit model using a technetium-99m-labelled anti-fibrin monoclonal antibody.

Technetium-99 m (99mTc)-labelled conjugates of an anti-fibrin monoclonal antibody, DD-3B6/22, have been assessed for their detection of vascular thrombi in a rabbit model. DD-3B6/22 binds to a D-dimer epitope present on cross-linked fibrin but absent from the fibrin monomer or fibrinogen. Injection of a 99mTc-labelled Fab' fragment of DD-3B6/22 allowed delineation of model thrombi as early as 30 min postinjection (p.i.) with optimal localization at 4-5 h. Thrombus label uptake at 4 h p.i. was 0.304 +/- 0.106% injected dose/g (% ID/g) compared with 0.022 +/- 0.001% ID/g after the injection of a control Fab' fragment. These results suggest that the 99mTc-labelled Fab' fragment of DD-3B6/22 has excellent potential for scintigraphic detection of vascular thrombi in humans.

Animals↗

Technetium-99 m labelling of DD-3B6/22 antifibrin monoclonal antibody fragment Fab' for thrombus imaging.

The antifibrin DD-3B6/22 monoclonal antibody Fab' fragment, a murine immunoglobulin, IgG3, has been labelled with technetium-99 m (99mTc) via a transchelation reaction, to specific activity in excess of 30 mCi/mg protein. The radiolabelling of Fab' was dependent on time, temperature, pH, antibody concentrations and nature of intermediary transchelation complex used. The resultant radioconjugate was stable in vitro and in vivo. Blood clearance of 99mTc-Fab' in rat followed two compartment kinetics with the half time of the fast phase being 0.5 h. The main route of excretion was via the kidneys with little uptake indicated by other tissues. The results suggest that the inherent specificity of the antibody, small molecular size, rapid plasma clearance, high specific radioactivity, together with the physical properties of the 99mTc label, combine to make this labelled monoclonal antibody (MoAb), potentially suitable as a radiopharmaceutical for the scintigraphic detection of thrombi in humans.

Animals↗

Effect of metabolic alterations on the accumulation of technetium-99m-labeled d,l-HMPAO in slices of rat cerebral cortex.

It is widely recognized that the distribution of technetium-99m-labeled d,l-hexamethylpropylene amine oxime (99mTc-HMPAO) in the brain is determined by the regional blood flow. However, other factors may affect this process including the metabolism of the brain tissue. To examine this possibility we studied the effects of metabolic alterations on 99mTc-HMPAO uptake in rat brain cortex slices, with concurrent measurement of oxygen consumption (QO2). 99mTc-HMPAO uptake was determined by incubating slices of rat cerebral cortex at 37 degrees C in Krebs-Ringer phosphate glucose medium containing 99mTc-HMPAO with and without test substances. Differential gradients for 99mTc activity between the tissue and the suspending medium (T/M ratio) were derived from the equation T/M[99mTc] = counts per gram of tissue/counts per milliliter of medium. The QO2 of the brain slices was measured using a biological oxygen monitor equipped with a polarographic oxygen probe. Inhibitors affecting oxidative phosphorylation caused parallel suppression of the T/M ratio and QO2. Agents that uncouple oxidation from phosphorylation increased the QO2 and decreased the T/M ratio. Incubation of slices at 22 degrees C depressed the T/M ratio and QO2. The presence of inhibitors of oxidative phosphorylation in the incubation medium increased the release of 99mTc activity from slices that had been prelabeled with 99mTc-HMPAO. These findings suggest that the altered metabolic status of the brain tissue modulates the kinetics and net accumulation of 99mTc-HMPAO at the cellular level by either depressing uptake, increasing back-diffusion, or both.

2,4-Dinitrophenol↗

Pulmonary calcification in hemodialyzed patients detected by technetium-99m diphosphonate scanning.

Metastatic pulmonary calcification, a well-known complication in patients with chronic disease, has been demonstrated postmortem in patients with a negative chest X-ray. Recently, scintigrams with bone-seeking radionuclides have been used to detect such subclinical pulmonary calcium deposits. We describe 23 patients on maintenance hemodialysis with no evidence of pulmonary calcification on chest X-ray who were prospectively studied by lung scanning with a bone-seeking radionuclide and pulmonary function testing. Of the 23 patients, 14 (61%) had a positive technetium-99m diphosphonate (99mTc-DP) scan (group 1). These patients were on dialysis 38 +/- 5 months compared with 12 +/- 4 months in 9 patients with a negative scan (group 2) (P less than 0.01). Age, sex, blood pressure, hematocrit, serum calcium, phosphorous, bicarbonate, magnesium, and calcium X phosphorus product, as well as parathyroid hormone level did not differ between the two groups. Of 10 group-1 patients tested, 7 had abnormal pulmonary diffusion capacity compared with non in 5 group-2 patients tested (P = 0.014). Histologic examination of the lung in 1 group-1 patients who expired revealed calcification (amorphous on X-ray diffraction), whereas none was found in 1 group-2 patients autopsied. These observations suggest that in patients on maintenance hemodialysis, pulmonary scanning with 99mTc-DP is a sensitive method for detecting pulmonary metastatic calcification, which may be associated with an abnormality in pulmonary diffusion capacity.

Adult↗

Technetium-99m-sestamethoxyisobutylisonitrile scan as a predictor of chemotherapy response in malignant lymphomas compared with P-glycoprotein expression, multidrug resistance-related protein expression and other prognosis factors.

The purpose of the present study was to predict the response of malignant lymphomas (MLs) to chemotherapy using technetium-99m methoxyisobutylisonitrile (Tc-MIBI) scan and to compare it with the predictive ability of P-glycoprotein (P-gp) expression, multidrug resistance-related protein (MRP) expression and other prognosis factors. Twenty-five ML patients were enrolled in this study prior to initiation of chemotherapy. Images were obtained 10 min after intravenous injection of Tc-MIBI, interpreted visually and the tumour-to-background (T/B) ratios calculated. Immunohistochemical analyses were performed on sections of the biopsy specimens to determine P-gp and MRP expression. Chemotherapy response was evaluated in the first 1-2 years after completion of chemotherapy. The mean T/B ratio of the 15 patients with a good response (3.3 +/- 0.6) was significantly higher than that of the 10 patients with a poor response (1.2 +/- 0.1). All 15 patients with a good chemotherapy response had positive Tc-MIBI scan results and negative P-gp and MRP expression. All 10 patients with a poor response had negative Tc-MIBI scan results and either positive P-gp or MRP expression. Other prognosis factors showed no significant difference in the incidence of good and poor responses. Tc-MIBI scan results represent P-gp or MRP expression more accurately than other prognosis factors and predict the chemotherapy response in ML patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

(99m)Technetium pentavalent dimercaptosuccinic acid scintigraphy in the follow-up of clinically nonfunctioning pituitary adenomas after radiotherapy.

BACKGROUND: It is still difficult to differentiate pituitary adenoma remnants from postradiotherapy fibrosis by computed tomography (CT) or magnetic resonance imaging (MRI), especially in patients with clinically nonfunctioning pituitary adenomas (NFA), lacking circulating markers to follow disease progression or cure. OBJECTIVE: We investigated the usefulness of scintigraphy with technetium-99m pentavalent dimercaptosuccinic acid [(99m)Tc(V)DMSA], shown previously to detect most pituitary GH- and PRL-secreting adenomas and NFA, with tumour-to-background ratios (T/B) as high as 25-fold. PATIENTS: Eighteen patients with NFA (study group), 10 patients with GH- and three patients with PRL-secreting adenomas (control group), all of whom had undergone previous surgery. DESIGN: The study was an open longitudinal design. Pituitary CT/MRI and (99m)Tc(V)DMSA scintigraphy was performed before and 1, 3 and 5 years after conventional radiotherapy. Tumour size was measured as maximal diameter of the residual lesion, while uptake of (99m)Tc(V)DMSA was measured as a T/B ratio. RESULTS: At study entry, pituitary (99m)Tc(V)DMSA uptake was found in 13 NFA (72.2%), seven GH-secreting (70%) and all PRL-secreting adenomas; remnant tumour was documented by CT/MRI in all 31 patients. Maximal remnant diameter was significantly higher in patients with positive (13.3 +/- 0.9 mm) than in those with negative scintigraphy (7.0 +/- 0.3 mm, P < 0.001). During the 5-year follow-up postradiotherapy, a significant decrease in (99m)Tc(V)DMSA uptake (9.7 +/- 0.8 vs. 3.2 +/- 0.5, P < 0.0001) occurred in all but three patients. Two NFA patients died of tumour invasion 19 and 36 months after radiotherapy and one acromegalic patient had no change in his hormone levels. In the eight negative patients (five NFA and three GH), scintigraphy remained negative throughout follow-up. A remarkable shrinkage of the remnant tumour was observed in both the patients with negative (from 7.0 +/- 0.3 to 1.9 +/- 0.6 mm, P < 0.001) and in those with positive scintigraphy (from 13.3 +/- 0.9 to 7.3 +/- 0.6 mm, P < 0.001). At the end of the study, CT/MRI showed evident remnant tumour in 13 of 16 NFA (81.2%), nine GH-secreting (90%) and all three prolactinomas (100%), while the scintigraphy was negative (T/B < 1) or faintly positive (T/B 1-2) in eight of 16 NFA (50%), five GH-secreting (50%) and one prolactinoma (33.3%). CONCLUSIONS: Functional imaging of pituitary remnant adenomas (> 10 mm in size) by (99m)Tc(V)DMSA depicts viable pituitary adenoma remnants. This approach may be of clinical value in patients with clinically nonfunctioning adenomas to monitor the effects of radiotherapy.

Adenoma↗

Dual phase 99m-technetium Sestamibi imaging with single photon emission computed tomography in primary hyperparathyroidism: influence on surgery.

The purposes of this study were to determine the positive and negative predictive values of 99m Technetium (99mTc) Sestamibi dual phase imaging with single photon emission computed tomography (SPECT) for parathyroid adenomata or hyperplasia and the effect of preoperative localization on duration of surgery. We reviewed 33 adults (14 men, 19 women; mean age 53 years) with newly diagnosed primary hyperparathyroidism who underwent neck exploration. The duration of surgery for this cohort was compared with a group of historical controls (n = 53) who underwent surgery without preoperative SPECT. At surgery, there were 21 adenomata (including one carcinoma), 10 patients with hyperplasia and two with no pathology detected. The positive predictive values (PPV) for adenomata and hyperplasia were 95% and 100%, respectively. The negative predictive values (NPV) for these entities were 67% and 22%, respectively. The mean weight of adenomata detected was 3.4 g (range 0.2-17 g). Mean duration of surgery was 112.6 min as compared with 113 min in the historical controls (P = not significant). We conclude that 99mTc Sestamibi dual phase imaging with SPECT has an excellent PPV for parathyroid adenomata and hyperplasia, but does not contribute to reduced duration of surgery in patients undergoing neck exploration for the first time. The NPV is low, suggesting that a negative result does not exclude an adenoma or hyperplasia.

Adult↗

Impact of arterial occlusion during partial nephrectomy on residual renal function: an evaluation with (99m)technetium-dimercaptosuccinic acid scintigraphy.

BACKGROUND: Partial nephrectomy (PNx) has been performed with temporary renal arterial occlusion and in situ renal hypothermia (conventional PNx). However, the impact of temporary renal arterial occlusion on residual renal function has not been well assessed. To address this question, we performed renal scintigraphy with (99m)technetium-dimercaptosuccinic acid (DMSA) for the quantitative measurement of postoperative residual renal function after conventional PNx and partial nephrectomy without arterial occlusion (non-clamping PNx). METHODS: Thirty-four patients underwent postoperative DMSA scintigraphy after PNx for renal cell carcinoma. No obvious difference in preoperative renal function between the diseased kidney and the contralateral kidney was found in any of the patients. Of these patients, 24 underwent conventional PNx, and 10 underwent non-clamping PNx. Residual renal function was evaluated using the relative DMSA uptake of the operated kidney. RESULTS: The relative DMSA uptake of the operated kidney was 39.9 +/- 7.3% (25.1-58.8) after conventional PNx compared to 34.8 +/- 8.9% (13.5-45.5) after non-clamping PNx. This difference was not statistically significant (P = 0.15). Total ischemic time during conventional PNx had no adverse influence on the residual renal function. In the analysis of the other determinant factors influencing residual renal function, tumor size was the only significant factor that inversely correlated with the relative DMSA uptake. CONCLUSION: Our results showed that arterial clamping during PNx has no negative impact on the functional residual capacity as long as insitu renal hypothermia is adequately performed.

Adult↗

Sentinel lymph node identification for patients with breast cancer using large-size radiotracer particles: technetium-99m-labeled tin colloids produced excellent results.

Sentinel lymph node (SLN) biopsies using radioactive tracers have been reported to detect the metastatic status of the axillary lymph nodes in breast cancer patients. However, the optimal radioactive tracer particle sizes remain to be determined. In this study, identification of SLNs with large radiolabeled tin colloid particles was evaluated. Seventy-five patients with T1-2, N0 breast cancer were enrolled. Two hours prior to surgery, 1 to 2.5 mL technetium-99m-labeled tin colloid particles were injected around the tumor under ultrasonographic guidance. Immediately before the operation, dye fluids were also injected around the tumor to increase the interstitial pressure. After axillary dissection, lymph nodes with x100 or more uptake of radioactivity than the mean of the other lymph nodes are considered to be SLN. All lymph nodes from the axillary dissections were pathologically investigated, and the characteristics of SLNs were evaluated. SLNs were clearly identified in 74 of 75 patients (98.7%). Of 37 patients without SLN metastasis, pathological investigation revealed no further involvement of the remaining non-SLNs. The SLNs tended to be larger in size, and more than 50% were located in the lower medial site of the axilla. This is the first study to show that SLNs could successfully be identified with radiolabeled tin colloid particles. When SLNs were negative for metastases, non-SLNs were always negative.

Breast Neoplasms↗