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PubMed2001

A novel technetium-99m radioligand for the 5-HT(1A) receptor derived from desmethyl-WAY-100635 (DWAY).

This paper reports the synthesis, biological evaluation and in vitro autoradiography of a new technetium-99m radioligand with high affinity for the 5-HT(1A) receptor. The neutral complex combines an N(2)S(2) diamine dithiol (DADT) ligand as complexing moiety for oxotechnetium(V) and a 2-(1-piperazino)phenol via a 6-carbon alkyl chain, derived from desmethyl-WAY 100635 (DWAY). The complex displays an IC(50) value for the 5-HT(1A) receptor of 1.29 n M against the selective 5-HT(1A) agonist [(3)H]8-OH-DPAT, a moderate selectivity towards the alpha(1)-adrenergic receptor (IC(50) of 8.1 n M against [(3)H]prazosin) and a good selectivity for the D(2) receptor (IC(50) of 192 n M against [(3)H]spiperone) and the 5-HT(2A)receptor (IC(50) of 922 n M against [(3)H]ketanserin). Biodistribution studies in rats show an initial brain uptake of 0.56%+/-0.07% ID 2.5 min p.i. In vitro autoradiographic studies of the (99m)Tc complex in rat brains indicate a strong specific accumulation of the radioactivity in 5-HT(1A) receptor-rich brain regions.

Animals↗
PubMed2001

Accuracy of technetium-99m sestamibi scintimammography and X-ray mammography in premenopausal women with suspected breast cancer.

The aim of this study was to evaluate the usefulness of technetium-99m sestamibi scintimammography (SSM) and combined use of SSM and X-ray mammography (MG) in premenopausal patients with small (< or =2 cm) suspicious breast lesions. Eighty-seven premenopausal women (median age 47 years, range 32-52) with breast lesions ranging from 4 to 20 mm in greatest diameter (median 12 mm) and detected by MG, underwent SSM prior to open breast biopsy. A planar camera and single-photon emission tomography (SPET) technique were used in 23 (26.4%) and 64 (73.6%) patients, respectively. At histological examination, 72 (82.8%) breast cancers (pT1a=3, pT1b=27, pT1c=42) and 15 (17.2%) benign masses were found. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MG and SSM were 80.6% vs 80.6%, 60.0% vs 93.3% (P<0.05), 90.6% vs 98.3%, 39.1% vs 50.0% and 77.0% vs 82.8%, respectively. MG + SSM together had a sensitivity of 94.4% (P<0.05 vs SSM alone) and an accuracy of 82.8% for the detection of breast cancer. Tumours undetected by both MG and SSM were significantly (P<0.05) smaller than those correctly diagnosed. Patients with false-negative MG were younger (P<0.05) than those with tumours correctly detected, while SSM sensitivity was independent (P=NS) of age. In conclusion, in premenopausal patients with small breast lesions, the sensitivity of SSM and MG is similar (P=NS), whereas the specificity of SSM is significantly higher (P<0.05) than that of MG. Furthermore, the combination of MG and SSM offers significantly improved sensitivity and accuracy in comparison with the individual techniques, suggesting a complementary role of SSM in the detection of breast cancer in younger patients.

Breast↗
PubMed2002

Evaluation of MS-209, a novel multidrug-resistance-reversing agent, in tumour-bearing mice by technetium-99m-MIBI imaging.

MS-209 is a newly synthesised multidrug-resistance (MDR)-reversing agent with few side-effects. In this study, we evaluated the effect of MS-209 on P-glycoprotein (Pgp)-positive tumours in mice by means of technetium-99m methoxyisobutylisonitrile (MIBI) imaging. Mice received Pgp-negative KB-3-1 or Pgp-positive KB-C1 cell xenografts. KB-3-1-bearing mice were administered 0 or 100 mg/kg of MS-209 (groups S0 and S100, respectively), and KB-C1-bearing mice 0, 50, 100 or 200 mg/kg (groups R0, R50, R100 and R200, respectively), 30 min before imaging studies. Dynamic 99mTc-MIBI images were acquired for 30 min, followed by biodistribution studies. Washout of 99mTc-MIBI from the tumours was faster in group R0 than in group S0 on visual analysis, and the washout half-time estimated by region of interest analysis was shorter in group R0 than in group S0. Biodistribution studies revealed that 99mTc-MIBI accumulation in tumours (expressed as %ID/g) was also lower in group R0 than in group S0. MS-209 delayed the 99mTc-MIBI washout from KB-C1 tumours. Washout half-time was longer in groups R50, R100 and R200 than in group R0. A higher %ID/g was observed in groups R100 and R200 than in group R0. In KB-3-1 tumours, MS-209 had no effect on the washout half-time or the %ID/g. This study demonstrated that MS-209 increases the 99mTc-MIBI accumulation in Pgp-positive tumours. The MDR-reversing effect of MS-209 could be effectively evaluated with 99mTc-MIBI visually and non-invasively in vivo. 99mTc-MIBI imaging with MS-209 prior to chemotherapy should contribute significantly to the treatment strategy in patients with multidrug-resistant tumours.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Technetium-99m labelled fluconazole and antimicrobial peptides for imaging of Candida albicans and Aspergillus fumigatus infections.

The aim of this study was to investigate whether technetium-99m labelled fluconazole can distinguish fungal from bacterial infections. Fluconazole was labelled with (99m)Tc and radiochemical analysis showed less than 5% impurities. The labelling solution was injected into animals with experimental infections. For comparison, we used two peptides for infection detection, i.e. UBI 29-41 and hLF 1-11, and human IgG, all labelled with (99m)Tc. Mice were infected with Candida albicans or injected with heat-killed C. albicans or lipopolysaccharides to induce sterile inflammation. Also, mice were infected with Staphylococcus aureus or Klebsiella pneumoniae. Next, accumulation of (99m)Tc-fluconazole and (99m)Tc-labelled peptides/IgG at affected sites was determined scintigraphically. (99m)Tc-fluconazole detected C. albicans infections (T/NT ratio=3.6+/-0.47) without visualising bacterial infections (T/NT ratio=1.3+/-0.04) or sterile inflammatory processes (heat-killed C. albicans: T/NT ratio=1.3+/-0.2; lipopolysaccharide: T/NT ratio=1.4+/-0.1). C. albicans infections were already seen within the first hour after injection of (99m)Tc-fluconazole (T/NT ratio=3.1+/-0.2). A good correlation (R(2)=0.864; P<0.05) between T/NT ratios for this tracer and the number of viable C. albicans was found. Although (99m)Tc-UBI 29-41 and (99m)Tc-hLF 1-11 were able to distinguish C. albicans infections from sterile inflammatory processes in mice, these (99m)Tc-labelled peptides did not distinguish these fungal infections from bacterial infections. It is concluded that (99m)Tc-fluconazole distinguishes infections with C. albicans from bacterial infections and sterile inflammations.

Animals↗
PubMed2002

Technetium-99m methoxyisobutylisonitrile imaging for parathyroid adenoma: relationship to P-glycoprotein or multidrug resistance-related protein expression.

Gland size has been reported to have a major influence on localisation of parathyroid adenomas by technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) imaging. It has also been suggested that P-glycoprotein (Pgp) expression in parathyroid adenomas may influence localisation because false negative studies have been reported with large tumours and true positives with very small tumours. Therefore, the purpose of this study was to retrospectively evaluate the relationship between (99m)Tc-MIBI parathyroid imaging results and Pgp or multidrug resistance-related protein (MRP) expression in parathyroid adenomas. Before surgery, 47 patients with large parathyroid adenomas (larger than 1.5 g) underwent early and delayed parathyroid imaging, 10 min and 2 h after intravenous injection of (99m)Tc-MIBI. Immunohistochemical analyses (IHA) were performed, using multiple non-consecutive sections of the operative specimens, to detect Pgp or MRP expression. According to the results of IHA, the 34 parathyroid adenomas were separated into four groups: (1) three adenomas positive for both Pgp and MRP expression, (2) one adenoma positive for Pgp but negative for MRP expression, (3) four adenomas negative for Pgp but positive for MRP expression and (4) 39 adenomas with negative for both Pgp and MRP expression. All 39 adenomas in group 4 could be detected by (99m)Tc-MIBI parathyroid imaging. None of the eight adenomas in groups 1-3 could be detected by (99m)Tc-MIBI parathyroid imaging ( P<0.05). It is concluded that not only the size of parathyroid adenomas but also significant Pgp or MRP expression limits the sensitivity of (99m)Tc-MIBI imaging in localising parathyroid adenomas preoperatively.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2002

Is furosemide administration effective in improving the accuracy of determination of differential renal function by means of technetium-99m DMSA in patients with hydronephrosis.

It has been suggested that determination of differential renal function (DRF)using technetium-99m dimercaptosuccinic acid (DMSA) may lead to overestimation of the function of an obstructed kidney in patients with excretion abnormalities owing to pelvic retention of DMSA. Recently published guidelines have recommended use of furosemide injection when calculating DRF in these particular patients. The aim of this study was to evaluate the effect of diuretic administration on the determination of DRF using DMSA scintigraphy. For this purpose, 19 patients, aged from 1 month to 69 years (19.4+/-24.8 years, 15 males, 4 females), in whom pelvic retention had been documented by diuresis scintigraphy were included in the study. DMSA scintigraphy was performed in all patients 2-4 h after injection and six planar images were obtained. Immediately after the standard study, furosemide was injected in all patients, and 30 min later the same number of images was obtained. DRF was calculated for each patient and from each DMSA study by using the arithmetic mean method. The difference between two studies (DMSA scintigraphy with or without furosemide administration and diuresis scintigraphy) was expressed as a percentage of the mean value of the two studies (the DRF value of the affected kidney was thus taken into account). The mean of the differences represented the systemic bias and the SD of the mean of the differences represented the precision of the technique. In seven patients, diuresis renography revealed an obstructive curve pattern. We did not observe any significant difference between the DRF values obtained before and after diuretic administration ( P>0.5). When we compared DRF values obtained from standard and from diuretic DMSA studies, the mean of the differences was only 0.3% and the SD was only 1.2%. There was also no significant difference in DRF between patients with the obstructive curve pattern and those with a dilated renogram curve pattern (with washout of activity during the second phase of the study) ( P>0.1). In conclusion, we did not observe interference from pelvicalyceal activity in patients with documented pelvic retention and infer that diuretic administration may be a useless intervention for improving the accuracy of determination of DRF.

Adolescent↗
PubMed2003

Peritumoural versus subareolar administration of technetium-99m nanocolloid for sentinel lymph node detection in breast cancer: preliminary results of a prospective intra-individual comparative study.

The scintigraphic detection of sentinel lymph nodes (SNs) in early-stage breast cancer is a widely accepted diagnostic method. However, which radiotracer administration mode should be used is still controversial. This prospective study aimed to intra-individually compare the detection rates obtained after peritumoural versus subareolar injection with regard to SN number and localisation. Fifty-one women (age, 32-76 years) with breast cancer were investigated on two consecutive days. On day 1, 140-400 MBq technetium-99m nanocolloid was injected along the peripheral tumour margins. Static lymphoscintigrams of the axilla, thorax and neck were taken in various views 1 and 19 h p.i. On day 2, 10 MBq (99m)Tc-nanocolloid was injected subareolarly in the clock position of the tumour and dynamic and static scans were performed immediately. Thereafter, 30 MBq (99m)Tc-nanocolloid was administered peri-subareolarly and lymphoscintigrams were acquired in a dynamic and static manner. In 49/51 women, the different injection techniques disclosed the identical number and location of SNs in the axilla. In seven patients, the peritumoural injection detected additional SNs in the parasternal group. Axillary SNs were detected as early as 2-15 min following subareolar injection, both in the clock position and peri-subareolarly, as compared with about 1 h after peritumoural administration. Sixteen patients showed at least one tumour-positive SN, and nine also had tumour-positive non-SNs. One patient with a tumour-negative SN, visualised concordantly by both subareolar and peritumoural administration, demonstrated two metastatic non-SNs, yielding a false-negative rate of 5.9%. In conclusion, a simple subareolar injection in the clock position is sufficient for SN detection in breast cancer, if it is accepted that parasternal lymph node detection has no therapeutic consequences.

Adult↗
PubMed2004

Subareolar injection of technetium-99m nanocolloid yields reliable data on the axillary lymph node tumour status in breast cancer patients with previous manipulations on the primary tumour: a prospective study of 117 patients.

According to recently published guidelines, histological clarification by interventional techniques should be undertaken before planning the surgical management of patients with breast carcinoma. In patients with previous manipulations on the primary tumour, peritumoural injection in the context of preoperative scintigraphic detection of the sentinel lymph nodes is not possible. The aim of this prospective study was to clarify whether subareolar injection of nanocolloid can yield reliable data on the axillary lymph node tumour status in breast cancer patients with previous manipulations on the primary tumour. To date, 117 women (age 31-80 years) with breast carcinoma have been enrolled. All of these patients had undergone a biopsy (n=88) or surgery on the primary tumour (n=29) and were without clinical suspicion of lymph node metastases. Subareolar injection of 40 MBq technetium-99m nanocolloid was carried out in at least eight deposits around the areolar margin [one deposit in the middle of each quadrant and one deposit at each quadrant intersection (0.05 ml/deposit)]. Immediately after injection, dynamic and static lymphoscintigraphy of the axillary, thoracic and cervical areas was performed in various views with a gamma camera (LEAP collimator, 256x256 matrix). Lymphatic drainage was directed exclusively to the ipsilateral axilla. Sentinel lymph node biopsy and elective dissection of axillary lymph nodes were performed in all patients. All lymph nodes removed were examined by histology and immunohistochemistry. In 26 patients, lymph node metastases were found in the sentinel lymph nodes. In six of them, non-sentinel lymph nodes also showed tumour involvement. In the remaining 91 patients, lymph node metastases could be found neither in sentinel lymph nodes nor in non-sentinel lymph nodes. In conclusion, subareolar nanocolloid injection can yield reliable information on the axillary lymph node tumour status in patients with previous manipulations on the primary tumour in the breast.

Adult↗
PubMed2004

Technetium-99m sestamibi brain SPECT in the follow-up of glioma for evaluation of response to chemotherapy: first results.

The initial treatment of high-grade glioma often consists of surgery and radiation therapy. Chemotherapy is used in cases of recurrence or after incomplete surgery. Because of the many potential serious side-effects of chemotherapy, early tumour response evaluation is necessary to enable clinicians to adapt the treatment. However, response monitoring with computed tomography (CT) or magnetic resonance imaging (MRI) is often difficult. The aim of this study was to assess the value of repeated technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) single-photon emission computerised tomography (SPECT) for this purpose. Fifteen patients with malignant glioma were investigated with MIBI SPECT. Imaging was performed 1 h after the intravenous injection of 555 MBq of (99m)Tc-MIBI, using a dedicated SPECT system (Tomomatic 564, Medimatic, Denmark). Overall, 57 investigations were performed. A MIBI uptake index was computed as the ratio of counts in the lesion to those in the contralateral region. Previous study had shown a cut-off value of 2.0 to be appropriate. SPECT indices were compared with neurological evaluation, CT or MRI. This assessment was performed every 4 months during and after the treatment. Six patients showed an increased MIBI index associated with clinical or radiological progression of disease during chemotherapy. After an initial response to therapy, three patients showed an increased MIBI index despite chemotherapy, demonstrating secondary resistance to therapy. Six patients showed a decreased MIBI index, demonstrating a good response to therapy. The first nine patients died shortly after the last SPECT scan (average duration of survival, 4 months). The therapeutic protocol was modified in six cases, but successfully so in only two. In some cases, tumour progression was diagnosed earlier with SPECT than on the basis of clinical or MRI signs. Early response or resistance to chemotherapy is detectable by(99m)Tc-MIBI SPECT. Therefore this functional imaging modality could be considered as a valuable tool to permit effective adaptation of the therapeutic regimen in patients treated for recurrent high-grade glioma.

Adult↗
PubMed2000

Technetium-99m DTPA inhalation scintigraphy in patients treated with fluoxetine and maprotiline: preliminary results.

Drug-metabolising enzymatic activities have been detected in tracheobronchiolar, bronchiolar and alveolar regions in the lungs. Induction of phospholipidosis by amine drugs such as clorphentermine has also been shown. This study aimed to investigate the effect of fluoxetine and maprotiline, which contain amine groups in their structure, on pulmonary epithelial membrane permeability. Twenty-seven patients (mean age 36+/-12 years) with various psychiatric problems, of whom 17 were treated with fluoxetine and 10 with maprotiline, were included in this study. Technetium-99m diethylene triamine penta-acetic acid (DTPA) aerosol inhalation scintigraphy was performed before and after 4-6 weeks of therapy. Following the inhalation of 1480 MBq 99mTc-DTPA for 3 min, lung images in a 64x64 matrix were obtained every minute for 30 min. Regions of interest were drawn around the periphery of the lungs and on the major airways. Clearance half-times (T 1/2) were calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was calculated on the first-minute image. There was no difference between the clearance rates of 99mTc-DTPA before and after therapy for either the fluoxetine or the maprotiline group. After therapy, a significant decrease in PI was found in patients treated with fluoxetine (PI values before and after therapy: 0.53+/-0.03 and 0.49+/-0.05 respectively, P< or =0.05). This finding might have been due to the induction of increased synaptic serotonin (5-HT) by fluoxetine, which acts by inhibiting the re-uptake of 5-HT on presynaptic membranes. Bronchoconstriction of small and medium airways may be caused by direct and indirect effects of 5-HT on smooth muscle contraction.

Administration, Inhalation↗
PubMed2000

A comparison of the overall first-pass kinetics of thallium-201 and technetium-99m MIBI in normoxic and low-flow ischaemic myocardium.

The specific impact of ischaemia on the myocardial kinetics of thallium-201 and technetium-99m 2-methoxy-2-isobutylisonitrile (MIBI) remains a matter of debate. Using an isolated heart model perfused with red blood cell-enhanced perfusate, we compared the overall first-pass kinetics of 201Tl and MIBI under haemodynamically stable conditions of low-flow ischaemia (> 50% reduction in normal coronary flow and a > or = 20 mmHg fall in systolic contraction pressure, n = 10) and normoxia (n = 11). For both 201Tl and MIBI, we found that under ischaemic conditions (as compared with normoxia) there was a higher initial net extraction fraction (201Tl: 0.78 +/- 0.03 vs 0.72 +/- 0.06, P = 0.006; MIBI: 0.49 +/- 0.10 vs 0.39 +/- 0.11, P = 0.03), a lower clearance rate in the 30 min following extraction (% decrease in cardiac uptake: 201Tl: 30 +/- 12 vs 47 +/- 14, P = 0.02; MIBI: 5 +/- 5 vs 13 +/- 11, P = 0.02) and a higher retention fraction at 30 min (20lTl: 0.54 +/- 0.10 vs 0.39 +/- 0.12, P = 0.004; MIBI: 0.46 +/- 0.08 vs 0.33 +/- 0.12, P = 0.01). Multivariate analyses, however, revealed that all myocardial kinetic parameters of both tracers were dependent only on coronary flow rates, without any additional significant impact of the presence of ischaemia or states of contractility or oxidative metabolism. We conclude that the myocardial fractional retention of both 201Tl and MIBI is strongly correlated with the decrease in coronary flow during ischaemia. This inverse relationship with coronary flow derives from both the flow-dependent increase in the initial myocardial extraction and the decrease in the subsequent myocardial washout of the tracers.

Animals↗
PubMed2000

Technetium-99m RP527, a GRP analogue for visualisation of GRP receptor-expressing malignancies: a feasibility study.

Gastrin-releasing peptide (GRP) receptor scintigraphy could allow prediction of response to GRP receptor-targeted treatment options, early non-invasive diagnosis and in vivo prognostic stratification of GRP receptor-positive tumours. This study reports on the imaging characteristics and efficacy for tumour detection of technetium-99m RP527, a 99mTc chelated targeting peptide derived from bombesin, which binds GRP receptors with high affinity. Ten patients (four men and six women, mean age 56.4 years) either suffering from metastasised prostate (n, number of patients = 4) or breast carcinoma (n=1) or presenting with a clinical diagnosis highly suggestive for breast carcinoma (n=5) were included in the study. In the latter five patients, 99mTc-RP527 scintigraphy was performed prior to diagnostic, e.g. biopsy, and staging examinations. Final diagnosis in these patients was breast carcinoma in all five. In all patients, whole-body planar scans and tomographic images were acquired 1 h and 5-6 h post injection of 555 MBq 99mTc-RP527 and tumour to normal tissue (T/N) ratios determined. 99mTc-RP527 showed specific uptake in four of six breast and one of four prostate carcinomas. T/N ratios derived from planar and tomographic images increased significantly (P<0.01) from 1.65 (SD 1.53) and 3.35 (SD 3.04) to 2.58 (SD 1.26) and 7.23 (SD 8.46), respectively. T/N ratios derived from tomographic images were consistently higher (P<0.01). The data presented suggest that 99mTc-RP527 results in specific tumour localisation and exhibits good imaging characteristics with a good T/N ratio that may be further enhanced by single-photon emission tomography.

Adult↗
PubMed2001

Assessment of leg oedema by dynamic lymphoscintigraphy with intradermal injection of technetium-99m human serum albumin and load produced by standing.

This study was a preliminary evaluation of the utility of dynamic lymphoscintigraphy with technetium-99m human serum albumin (HSA) and a load produced by standing in the assessment of lymphatic dysfunction in patients with leg oedema. The 71 subjects investigated included 53 patients with lymphoedema, six with venous occlusion alone and five with lymphovenous occlusion, as well as seven normal subjects. After intradermal injection of 99mTc-HSA into an interdigital space in each foot, dynamic scintigrams were recorded with the patient supine for 15 min. The subjects then stood in place and images were recorded for an additional 15 min. Relative changes in lymphatic tracer transport before and after standing were analysed on time-activity curves (TACs). This test was compared with a conventional test in a supine position in six patients with lymphoedema, and was repeated in five other patients with lymphoedema. It was found that in the normal limbs, a standing load activated tracer transport to the draining lymphatic vessels, resulting in a rapid stepwise increase in tracer activity, large spiking waves and a decreasing phase following a peak in tracer activity on TACs. In 59 lymphoedematous limbs, including some with a mild form of oedema without morphological abnormalities on scintigrams, this load failed to induce a sufficient activation of tracer transport, and the frequencies of each of the three normally appearing changes described above significantly decreased compared with those in the 14 normal limbs (P < 0.0001, P < 0.01 and P < 0.0001, respectively). In addition, there were significant reductions in the relative increases in maximum activity and clearance times after standing (both P < 0.0001). These abnormalities significantly correlated with the grade of severity of oedema. Six limbs with lymphovenous occlusion showed significant reductions in tracer transport compared to six limbs with venous occlusion. Lymphatic dysfunction was accentuated more by this test than by the conventional test, and repeated tests showed consistent results in the same individuals. It is concluded that under a standardized load, this quick test seems of value in providing a sensitive and objective assessment of lymphatic dysfunction in the lower limbs, and is also advantageous for image interpretation since accelerated tracer transport clearly visualizes compromised lymphatics. This test may also be helpful in distinguishing purely venous oedema from mixed lymphovenous disease.

Adult↗
PubMed2001

Predictive value of technetium-99m sestamibi in patients with multiple myeloma and potential role in the follow-up.

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI or setamibi) has recently been proposed for use in the evaluation of multiple myeloma (MM). The aims of this study were to investigate its potential predictive value in patients with MM and its possible role in the follow-up. Thirty patients with MM who had undergone two 99mTc-MIBI scintigraphic studies at least 2 months apart constituted the study group; 22 of them received chemotherapy in the interval between the two scans. The scans were classified as showing pattern N when only physiological uptake was present, pattern D when diffuse bone marrow uptake was observed, pattern F when areas of focal uptake of the tracer were evident, and pattern F + D when both D and F patterns were observed. Comparative 99mTc-MIBI scintigraphy was considered indicative of disease progression when there was a worsening of the pattern (i.e. from N to D, or from N or D to F or to F + D) or an increase in the pattern D semiquantitative score. It was considered indicative of disease improvement when the opposite trend was observed; otherwise, it was considered to document a stable condition. A significant association was observed between the baseline scintigraphic pattern and clinical status at follow-up in the group of patients evaluated after chemotherapy (chi 2 = 16.7, P < 0.05). A negative baseline 99mTc-MIBI scintigram showed a high predictive accuracy (100%) for remission, while the presence of pattern F or F + D was often associated with a less favourable outcome. A multivariate analysis showed that 99mTc-MIBI uptake pattern has an added value in relation to known prognostic variables such as C-reactive protein. 99mTc-MIBI scintigraphy patterns at follow-up were significantly associated with the clinical status evaluated after chemotherapy (chi 2 = 32.6, P < 0.0001). Considering pattern N as indicating remission, pattern D stable condition, and pattern F or F + D progressive disease, a high concordance between scintigraphic findings and clinical status was found in the 22 patients undergoing chemotherapy (91%). Variation in 99mTc-MIBI findings comparing baseline and follow-up evaluations was significantly associated with clinical status both in patients undergoing chemotherapy (chi 2 = 26.5, P < 0.0005) and in those not undergoing chemotherapy (chi 2 = 8.0, P < 0.005). In conclusion, the results of this study suggest a prognostic value of 99mTc-MIBI scintigraphy in patients with MM and a potential role during the follow-up.

Aged↗
PubMed2001

Use of technetium-99m HMPAO scintigraphy for the detection of amiodarone lung toxicity in a rabbit model.

Amiodarone (AD) is a very effective anti-arrhythmic drug, but its use is often associated with serious pulmonary complications such as pneumonitis and interstitial pulmonary disease. The aim of this study was to investigate the relationship between the amount of amiodarone intake (and the related development of lung toxicity) and the lung uptake of technetium-99m labelled D,L-hexamethylpropylene amine oxime (HMPAO). Eighteen white female New Zealand rabbits were divided into three groups and fed AD by gavage at doses of 10 (group A), 50 (group B) or 150 (group C) mg/kg daily. 99mTc-HMPAO scintigraphy was performed at baseline and after 1, 2, 3 and 4 weeks of drug intake. Anterior images of 1 min duration were acquired at 30 min after the injection of 37 MBq 99mTc-HMPAO. Regions of interest (ROIs) were drawn on the lungs (L) and the upper limb (B) as the background. L/B ratios were calculated using the mean counts. In groups A and B histopathological evaluation of the lungs of all rabbits was performed at the end of the 4 weeks of AD intake, while in group C it was performed at 2 weeks because of increased mortality. At baseline, mean L/B ratios for groups A, B and C were 2.8 +/- 0.3, 2.8 +/- 0.3 and 2.8 +/- 0.4, respectively. After 3 weeks of AD intake, L/B ratios increased to 4.1 +/- 0.6 and 4.8 +/- 0.6 in groups A and B, respectively. The L/B ratio was 3.6 +/- 0.2 after 1 week of AD intake in group C. The correlation coefficients between the lung uptake of 99mTc-HMPAO and AD doses for groups A, B and C were r = 0.51 (P = 0.037), r = 0.74 (P = 0.0002) and r = 0.96 (P = 0.0001), respectively. Histopathological findings related to AD lung toxicity, such as interstitial pneumonitis and foamy alveolar macrophages, were observed more frequently in groups B and C than in group A. According to our findings, 99mTc-HMPAO lung uptake is correlated with AD dose. 99mTc-HMPAO lung imaging can demonstrate AD-induced lung injury.

Amiodarone↗
PubMed2000

Technetium-99m labelled antimicrobial peptides discriminate between bacterial infections and sterile inflammations.

The aim of this study was to select technetium-99m labelled peptides that can discriminate between bacterial infections and sterile inflammations. For this purpose, we first assessed the binding of various 99mTc-labelled natural or synthetic peptides, which are based on the sequence of the human antimicrobial peptide ubiquicidin (UBI) or human lactoferrin (hLF), to bacteria and to leucocytes in vitro. In order to select peptides that preferentially bind to bacteria over host cells, radiolabelled peptides were injected into mice intraperitoneally infected with Klebsiella pneumoniae (K. pneumoniae) and the amount of radioactivity associated with the bacteria and with the leucocytes was quantitated. The next phase focussed on discrimination between bacterial infections and sterile inflammatory processes using 99mTc-labelled peptides in mice intramuscularly infected with various bacteria (e.g. multi-drug-resistant Staphylococcus aureus) and in animals that had been injected with lipopolysaccharides (LPS) of bacterial origin to create a sterile inflammatory process. Also, we studied the distribution of 99mTc-labelled UBI 29-41 and UBI 18-35 in rabbits having an experimental thigh muscle infection with K. pneumoniae and in rabbits injected with LPS. Based on the results of our in vitro and in vivo binding assays, two peptides, i.e. UBI 29-41 and UBI 18-35, were selected as possible candidates for infection imaging. The radiolabelled peptides can detect infections with both gram-positive and gram-negative bacteria in mice as early as 5-30 min after injection, with a target-to-non-target (T/NT) ratio between 2 and 3; maximum T/NT ratios were seen within 1 h after injection. In rabbits, high T/NT ratios (>5) for 99mTc-labelled UBI 29-41 were observed from 1 h after injection. No accumulation of the selected 99mTc-labelled UBI-derived peptides was observed in thighs of mice and rabbits previously injected with LPS. Scintigraphic investigation into the biodistribution of 99mTc-labelled UBI peptides revealed that these peptides were rapidly removed from the circulation by renal excretion. Similar data were observed for 99mTc-labelled defensin 1-3. Our data for 99mTc-labelled hLF and related peptides indicate that these compounds are less favourable for infection detection. Taken together, 99mTc-labelled UBI 18-35 and UBI 29-41 enable discrimination between bacterial infections and sterile inflammatory processes in both mice and rabbits. Based on their characteristics, we consider these peptides the candidates of preference for detection of bacterial infections in man.

Animals↗
PubMed1997

Role of technetium-99m sestamibi scintimammography and contrast-enhanced magnetic resonance imaging for the evaluation of indeterminate mammograms.

This study evaluated and compared technetium-99m sestamibi scintimammography (SMM) and breast magnetic resonance imaging (MRI) results in patients with indeterminate mammograms to determine whether either technique can improve the sensitivity and specificity for the diagnosis of breast carcinoma. From 123 consecutive patients who underwent physical examination, mammography, SMM, and histopathologic confirmation, a subgroup of 82 patients presenting with indeterminate mammograms was studied. Sixty-eight patients underwent contrast-enhanced MRI. SMM results were scored on the basis of the intensity and pattern of sestamibi uptake. MRI images were scored on the basis of signal intensity increase after administration of contrast material as well as the enhancement pattern and speed of gadolinium uptake. The results obtained with the two techniques were compared and related to the final histopathologic diagnoses. Considering indeterminate findings as positive, the sensitivity of SMM was 79% and the specificity, 70%. MRI displayed a sensitivity of 84% and a specificity of 49%. When indeterminate results were considered negative, the sensitivity and specificity of SMM were 62% and 83%, respectively. MRI revealed a sensitivity and specificity of 56% and 79%, respectively. The calculated sensitivities and specificities demonstrate the diagnostic limitations of both SMM and MRI in the evaluation of patients with indeterminate mammographic findings. Due to the higher specificity, SMM may be the preferred modality in the evaluation of selected patients with breast abnormalities.

Breast Diseases↗
PubMed1997

Ventilation/perfusion ratios and simultaneous dual-radionuclide single-photon emission tomography with krypton-81m and technetium-99m macroaggregated albumin.

To date, there has been neither a good method to clarify the three-dimensional distribution of pulmonary ventilation/perfusion (V. A/Q.) ratios, nor a convenient way to assess V.A/Q. inequality. The purpose of this study was to develop a functional image of pulmonary V.A/Q. ratios based on data acquired with simultaneous dual-radionuclide single-photon emission tomography (SPET) and to assess V.A/Q. unevenness through the V.A/Q. histogram in patients with various pulmonary diseases. Dual-radionuclide SPET was performed with technetium-99m macroaggregated albumin (MAA) and krypton-81m, with the patient in the supine position. After correction for linear cross-talk, the total acquisition counts of both radionuclides were equalized. The V.A/Q. ratio, which was calculated in each pixel by dividing the 81mKr count by the 99mTc-MAA count, was expressed as a V.A/Q. image. A histogram of the pixel number plotted against the V.A/Q. ratios was then produced and its centre of weight (CW) and standard deviation (SD) determined. Ten healthy volunteers and 46 patients [seven with pulmonary vascular disease (PVD), nine with pulmonary emphysema (PE), 18 with bronchogenic carcinoma and 12 with miscellaneous diseases] participated in this study. In normal volunteers, V.A/Q. ratios were generally even, but were slightly lower in dorsal regions. Patients with PVD had lobar and/or segmental areas with a high V.A/Q. ratio. Low V.A/Q. areas extended widely in patients with PE. Bronchogenic carcinoma exceeding 3 cm in diameter was detected as a very low V. A/Q. area. The SD of V.A/Q. ratios had a significant positive correlation both with A-aDO2 (r=0.64, P<0.001) and with cigarette smoking history (r=0.72, P<0.001). It is concluded that the V.A/Q. ratio image produced with simultaneous dual-radionuclide SPET using 99mTc-MAA and 81mKr is a unique and simple method for demonstrating the three-dimensional distribution of V.A/Q. ratios. The unevenness of V.A/Q. distribution can be assessed through the SD of the V.A/Q. histogram.

Adult↗