Clinical significance of abdominal scintigraphy using 99mTc-HMPAO-labelled leucocytes in patients with seronegative spondyloarthropathies

Abdominal scintigraphy shows silent gut inflammation in patients with spondyloarthropathies (Sp) without clinical evidence of gut inflammation. Abdominal scintigraphy images are different than those obtained in patients with ulcerative colitis or Crohn's disease and are not related to the anti-inflammatory drugs administered. The aim of this study was to examine the clinical associations of findings on abdominal scintigraphy in patients with Sp. A total of 204 Sp patients (European Spondylarthropathy Study Group 1991 criteria) and 54 non-Sp controls receiving non-steroidal anti-inflammatory drugs were studied. Abdominal scintigraphy images were obtained at 30 and 120 min after injection of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO)-labelled leucocytes. 99mTc-HMPAO-labelled leucocyte scans were positive in 104 Sp patients (50.9%) and in six non-Sp controls (2.9%) (P<0.001; OR=8.32; 95% CI=3.23-22.67). Silent gut inflammation was not associated with any of the following: age of onset, duration of evolution, sex, family history of Sp or psoriasis, articular manifestations, extra-articular manifestations, radiological findings or HLA-B27 positivity. Positive abdominal scintigraphy was associated with active disease (P < 0.0001; OR=52.7; 95% CI=19-145.6) and an increase in the C-reactive protein (P < 0.005; OR = 3.4; 95% CI = 1.5-7.4). It is concluded that (a) abdominal scintigraphy using 99mTc-HMPAO-labelled leucocytes is of value in detecting the silent gut inflammation in Sp patients, and (b) silent gut inflammation is related to the clinical activity, but is not associated with any particular type of illness or with HLA-B27.     

Abdominal scintigraphy using99mTc-HMPAO-labelled leucocytes in patients with seronegative spondylarthropathies without clinical evidence of inflammatory bowel disease

Abdominal scintigraphy with technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO)-labelled leucocytes is an excellent tool for evaluating disease extent and activity of intestinal lesions in patients with inflammatory bowel disease (IBD). In some cases of seronegative spondylarthropathies (SSp), IBD may remain subclinical. The aim of this study was to evaluate the presence of positive abdominal scintigraphy in patients with SSp and without clinical symptoms or signs of IBD. To this end we studied 32 patients with active SSp (European Spondylarthropathy Study Group 1991 criteria) without clinical evidence of IBD (eight had ankylosing spondylitis, four psoriatic arthritis, three reactive arthritis an 17 undifferentiated SSp) and 11 controls without SSp. All SSp and control patients received similar doses of non-steroidal anti-inflammatory drugs (NSAIDs). Abdominal scintigraphic images were obtained at 30 and 120 min after re-injection of^99mTc-HMPAO-labelled leucocytes. The^99mTc-HMPAO-labelled leucocyte scan was positive in 17 patients with SSp (53.1%) (six with ankylosing spondylitis, three with psoriatic arthritis, two with reactive arthritis and six with undifferentiated SSp). Fourteen patients scored from 2 to 4 on the intensity of uptake scale. The colon and terminal ileum were predominantly involved. Axial involvement was more frequent in patients with a positive scan than in patients with negative results (P<0.05) (64.7% vs 26.6%; odds ratio: 5). No control patient showed a positive scan. It is concluded that^99mTc-HMPAO-labelled leucocyte scan shows increased uptake among patients with SSp without evidence of IBD. These findings provide new evidence linking SSp with intestinal inflammation and suggest that in some cases a bowel-related process could contribute to the development of SSp. Longterm follow-up studies with more patients are necessary to evaluate the diagnostic and therapeutic implications of these results.     

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.     

FDG-PET, 99mTc-HMPAO white blood cell SPET and bone scintigraphy in the evaluation of painful total knee arthroplasties

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), technetium-99m hexamethylpropylene amine oxime (HMPAO)-labelled white blood cell (WBC) scintigraphy and bone scintigraphy were used in the evaluation of total knee arthroplasties (TKAs). We prospectively included 21 patients who had a three-phase bone scan for exclusion of infection of TKAs. Four hours after injection of 185 MBq ^99mTc-HMPAO-labelled WBCs, planar and single-photon emission tomographic (SPET) imaging was performed. Planar imaging was repeated at 24 h p.i. Consecutively images of the knees were obtained with a dedicated PET system 60 min following the injection of 370 MBq of FDG. Focal tracer uptake was scored on SPET and PET visually (0=no uptake, 4=intense uptake). In addition, SUV (standardised uptake value) per voxel was calculated from attenuation-corrected PET images using the MLAA algorithm. Focal uptake at the bone-prosthesis interface was used as the criterion for infection before and after correlation with the third phase of the bone scan. Final diagnosis was based on operative findings, culture and clinical outcome. In the infected TKAs, the WBC scan showed focal activity of grade 2 (n=2), 3 (n=1) or 4 (n=2). PET scan revealed focal activity of grade 4 (n=5) or 3 (n=1). WBC scan alone had a specificity for infection of 53% [positive predictive value (PPV) 42%, sensitivity 100%], compared with 73% for PET scan (PPV 60%, sensitivity 100%). Considering only lesions at the bone-prosthesis interface that were also present on the third phase of the bone scan, we found a specificity of 93% (PPV 83%) for WBC scan. Using these criteria, a specificity of 80% (PPV 67%) was obtained for PET scan. Two out of three false-positive PET scans were due to loosening of the TKA. It is concluded that WBC scintigraphy in combination with bone scintigraphy has a high specificity in the detection of infected TKAs. FDG-PET seems to offer no additional benefit.     

Clinical role of 99mTcO4/MIBI scan, ultrasound and intra-operative gamma probe in the performance of unilateral and minimally invasive surgery in primary hyperparathyroidism

The main purposes of this study were: (a) to investigate the efficacy of an imaging protocol based on the combination of ^99mTcO₄/MIBI scintigraphy and neck ultrasound (US) in selecting patients with primary hyperparathyroidism (HPT) for unilateral neck exploration, and (b) to help define the role of the intraoperative MIBI gamma probe (IMGP) technique in the performance of minimally invasive radio-guided surgery (MIRS). One hundred and forty-three consecutive patients with primary HPT were enrolled in the study. We used a modified ^99mTcO₄/MIBI scintigraphic procedure which included the oral administration of potassium perchlorate to cause rapid ^99mTcO₄ washout from the thyroid tissue, thereby permitting the acquisition of high-quality early MIBI images. A single-photon emission tomography (SPET) acquisition was also obtained in 21 patients, of whom seven had an enlarged parathyroid gland (EPG) in the mediastinum at planar scintigraphy and 14 had discordant scan/US findings for the presence of a cervical EPG. Neck US was performed in the same session as scintigraphy using a small-parts, high-resolution 10-MHz transducer. All patients were then operated on by the same surgical team. Quick PTH assay (QPTH) was used to measure PTH intraoperatively to confirm successful parathyroidectomy. In patients with scan/US evidence of a solitary EPG and with a normal thyroid gland, limited, unilateral neck surgery or, more recently, MIRS was planned (n=91). In patients with scan/US evidence of multiglandular disease (MGD) (n=21) or concomitant nodular goitre (n=24) or in patients with a negative scan/US evaluation (n=7), extensive bilateral neck exploration was planned (n=52). In 87 of the 91 patients (95.6%) in whom preoperative imaging indicated the presence of a solitary EPG and a normal thyroid gland, a single parathyroid adenoma was found at surgery, and these patients were treated by unilateral neck exploration or MIRS. In the remaining four patients of this group, conversion to bilateral neck exploration was required because parathyroid carcinoma (n=3) or MGD (n=1) was diagnosed at operation. In some cases SPET was helpful in better localising the EPG. In particular, in 5 of the 21 patients evaluated, SPET localised an EPG deep in the neck or mediastinum and at surgery a parathyroid adenoma was found in the paratracheal or para-oesophageal space. In 43 of the 46 patients (93.5%) who were candidates for MIRS, the IMGP technique allowed parathyroidectomy to be performed through a small, 2- to 2.5-cm skin incision with a short duration of intervention (mean 34 min). We conclude that: (a) The integrated scan/US imaging protocol that we used appears to be accurate in selecting patients with primary HPT for unilateral neck exploration. (b) In our series the most prevalent cause of bilateral neck exploration was the co-existence of a nodular goitre; thus accurate preoperative evaluation of the thyroid gland by dual-tracer scintigraphy and US imaging is strongly recommended in all patients with HPT. (c) SPET can provide the surgeon with useful information when an EPG is located deep in the neck or mediastinum. (d) IMGP appears to be a useful intraoperative device in HPT patients with solitary parathyroid adenomas and a normal thyroid gland, since it permits minimally invasive and time-saving surgery.     

99mTc-EDDA/HYNIC-TOC: a new 99mTc-labelled radiopharmaceutical for imaging somatostatin receptor-positive tumours: first clinical results and intra-patient comparison with 111In-labelled octreotide derivatives

[¹¹¹In-diethylene triamine penta-acetic acid-d-Phe¹]-octreotide (DTPA-octreotide) scintigraphy has gained widespread acceptance as a diagnostic clinical procedure in oncology for imaging somatostatin receptor-positive tumours. However, indium-111 as a radiolabel has several drawbacks, including limited availability, suboptimal gamma energy and high radiation burden to the patient. We have recently reported on the preclinical development of ^99mTc-EDDA/HYNIC-TOC, a new octreotide derivative which showed promising results both in vitro and in vivo. We now report our initial clinical experiences with this new radiopharmaceutical in ten oncological patients. The clinical diagnoses were: carcinoid syndrome (n=5), thyroid cancer (n=3), pancreatic cancer (n=1) and pituitary tumour (n=1). The biodistribution and kinetics of ^99mTc-EDDA/HYNIC-TOC were compared with those of ¹¹¹In-DTPA-octreotide in six cases, and with those of ¹¹¹In-DOTA-TOC in five cases. With the new tracer tumours were imaged within 15 min after injection and showed the highest target/non-target ratios 4 h after injection. Tumour uptake persisted up to 20 h p.i. The rate of blood clearance was similar to that of ¹¹¹In-DTPA-octreotide but faster than that of ¹¹¹In-DOTA-TOC, while urinary excretion was lower compared with the ¹¹¹In derivatives. Semi-quantitative region of interest analysis showed that ^99mTc-EDDA/HYNIC-TOC produced higher tumour/organ (target/non-target) ratios than the ¹¹¹In derivatives, especially in relation to heart and muscle. Significantly more lesions could be detected in ^99mTc images. We conclude that ^99mTc-EDDA/HYNIC-TOC shows better imaging properties for the identification of somatostatin receptor-positive tumour sites than currently available ¹¹¹In-labelled octreotide derivatives.     

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 2.8ǂ.3, 2.8ǂ.3 and 2. 8ǂ.4, respectively. After 3 weeks of AD intake, L/B ratios increased to 4.1ǂ.6 and 4.8ǂ.6 in groups A and B, respectively. The L/B ratio was 3.6ǂ.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.     

Technetium-99m sestamibi imaging to predict left ventricular ejection fraction outcome after revascularisation in patients with chronic coronary artery disease and left ventricular dysfunction: comparison between baseline and nitrate-enhanced imaging

Acceptance of technetium-99m sestamibi as a tracer of myocardial viability is growing, particularly when nitrate-enhanced imaging is used. However, few data are available on the ability of ^99mTc-sestamibi to predict the evolution of global left ventricular ejection fraction (EF). The aim of this study was to examine the ability of resting and nitrate ^99mTc-sestamibi single-photon emission tomography (SPET) to predict EF changes after revascularisation in patients who have chronic coronary artery disease with left ventricular dysfunction. Using baseline resting and nitrate ^99mTc-sestamibi SPET, we studied 61 patients scheduled for revascularisation because of left ventricular dysfunction. EF was estimated using two-dimensional echocardiography before and after the intervention. A post-revascularisation improvement of ̓ EF units was defined as significant. Using a 13-segment model, ^99mTc-sestamibi activity was quantified and the nitrate-induced activity changes calculated. Three different criteria for detecting viability (defined as post-revascularisation reversible dysfunction) in asynergic segments were compared: (1) resting ^99mTc-sestamibi activity ₨%; (2) nitrate ^99mTc-sestamibi activity ₭%; and (3) nitrate-induced increase >+10% or nitrate-induced increase h+10% and nitrate activity ₭%. EF increased significantly in 32 patients. The number of viable asynergic segments was significantly higher in these patients than in the remaining 29 subjects, and the difference was greater (P<0.0002) using definition (3) than using either baseline (P<0.002) or nitrate activity (P<0.0005). There was a significant relationship between EF changes and number of viable asynergic segments: Spearman R=0.38, P<0.005 using baseline; Spearman R=0.39, P<0.002 using nitrate activity; and Spearman R=0.55, P<0.000005 using definition (3). According to receiver operating characteristic (ROC) curve analysis, this last criterion achieved the best results (81% sensitivity, 69% specificity and 75% accuracy), with an area under the ROC curve of 0.838; this area was significantly larger than when using either baseline (0.744, P<0.02) or nitrate activity (0.747, P<0.005). ^99mTc-sestamibi SPET appears able to predict the evolution of global left ventricular EF after revascularisation, thereby confirming the value of ^99mTc-sestamibi as a tracer of myocardial viability. The combination of baseline resting and nitrate imaging seems to significantly improve the diagnostic accuracy of ^99mTc-sestamibi SPET for this particular purpose.     

The value of 99mTc-HMPAO labelled white blood cell scintigraphy in acute appendicitis patients with an equivocal clinical presentation

Various imaging studies can be performed in the evaluation of patients with a clinical presentation equivocal for acute appendicitis. One of these studies is technetium-99m hexamethylpropylene amine oxime (HMPAO) labelled white blood cell (WBC) scintigraphy. The aim of this study was to evaluate the accuracy and clinical value of ^99mTc-HMPAO WBC scintigraphy in the aforementioned group of patients. Forty-one patients who had acute right lower quadrant abdominal pain with a clinical presentation equivocal for acute appendicitis were included in the study. The anterior abdomen and pelvis were imaged up to 4 h after the injection of 125-300 MBq ^99mTc-HMPAO WBCs and the results were immediately reported to the surgeon before a decision was taken on whether to perform laparotomy. Diagnostic accuracy was established by the intra-operative findings and the histopathology in operated patients. In non-operated patients, absence of abdominal symptoms 1 month after scintigraphy and/or identification of another cause of abdominal pain was used to rule out acute appendicitis. There were 16 patients with positive scintigraphy and 81% of these patients were positive within 2 h post injection. There were no false-positive or false-negative results. We operated on 17 (41.4%) patients, and only one patient (5.9%) underwent unnecessary laparotomy. We conclude that ^99mTc-HMPAO WBC scintigraphy is a rapid, highly accurate method for the exclusion of acute appendicitis and that its use can lower the unnecessarily high laparotomy rate in patients with an equivocal clinical presentation.     

The role of 99mTc-MIBI scintigraphy in the assessment of MDR1 overexpression in patients with musculoskeletal sarcomas: comparison with therapy response

The occurrence of multidrug resistance (MDR), which is in part due to the overexpression of P-glycoprotein (Pgp), is a major problem in neoadjuvant therapy of malignant musculoskeletal tumours. The aim of this study was to investigate the role of technetium-99m hexakis-2-methoxyisobutylisonitrile (^99mTc-MIBI) scintigraphy for functional imaging of the MDR1 phenotype in patients with musculoskeletal sarcomas. We aimed to compare ^99mTc-MIBI uptake and washout kinetics with the expression of Pgp and with chemotherapy response. Twenty-five patients (16 males and 9 females, aged between 8 and 65 years) with malignant musculoskeletal tumours were studied. After injection of 555-740 MBq ^99mTc-MIBI, dynamic flow images of the involved area were obtained for 3 min, and planar images were acquired at 10 min and 1 h. From the dynamic images, a tumour perfusion index (TPI) was obtained using Patlak-Rutland analysis. Tumour to background (T/B) ratios of both early and delayed images and percent wash-out rate (WR%) of ^99mTc-MIBI were calculated. Immunohistochemical analysis of Pgp was performed on biopsy specimens and the degree of expression was graded according to a semiquantitative scoring system, from 0 to 6. After neoadjuvant therapy, tumour response was assessed by examining the ratio of viable cells and by detecting percent necrosis. Scintigraphic results were compared with Pgp status and therapy response. Irrespective of the Pgp status, all patients showed significant perfusion and ^99mTc-MIBI uptake in early images. There was not a significant correlation between T/B ratios of early and delayed images and Pgp expression. We observed a positive correlation between WR% and Pgp status (r=0.61, P<0.01), and the wash-out rate of ^99mTc-MIBI was significantly higher in patients with high Pgp expression than in those with a low Pgp score (33%Nj% vs 17%Nj%). Therapy response was determined in 21 of 25 patients, and in only 5 of 21 cases was the percent necrosis more than 90%. Neither Pgp expression rate nor WR% was found to show a significant correlation with percent necrosis in the bulk tumour specimens. In conclusion, the initial uptake of ^99mTc-MIBI in bone and soft tissue sarcomas did not correlate with Pgp expression. A relationship was found between the wash-out rate of ^99mTc-MIBI and the Pgp score, with a significant difference in WR% being observed between patients with high and patients with low Pgp expression.     

Bone marrow uptake of 99mTc-MIBI in patients with multiple myeloma

In a previous study, we showed the ability of technetium-99m methoxyisobutylisonitrile (^99mTc-MIBI) scan to identify active disease in patients with multiple myeloma (Eur J Nucl Med 1998; 25: 714-720). In particular, a semiquantitative score of the extension and intensity of bone marrow uptake was derived and correlated with both the clinical status of the disease and plasma cell bone marrow infiltration. In order to estimate quantitatively ^99mTc-MIBI bone marrow uptake and to verify the intracellular localization of the tracer, bone marrow samples obtained from 24 multiple myeloma patients, three patients with monoclonal gammopathy of undetermined significance (MGUS) and two healthy donors were studied for in vitro uptake. After centrifugation over Ficoll-Hypaque gradient, cell suspensions were incubated with ^99mTc-MIBI and the uptake was expressed as the percentage of radioactivity specifically retained within the cells. The cellular localization of the tracer was assessed by micro-autoradiography. Twenty-two out of 27 patients underwent ^99mTc-MIBI scan within a week of bone marrow sampling. Whole-body images were obtained 10 min after intravenous injection of 555 MBq of the tracer; the extension and intensity of ^99mTc-MIBI uptake were graded using the semiquantitative score. A statistically significant correlation was found between in vitro uptake of ^99mTc-MIBI and both plasma cell infiltration (Pearson's coefficient of correlation r=0.69, P<0.0001) and in vivo score (Spearman rank correlation coefficient r=0.60, P<0.01). No specific tracer uptake was found in bone marrow samples obtained from the two healthy donors. Micro-autoradiography showed localization of ^99mTc-MIBI inside the plasma cells infiltrating the bone marrow. Therefore, our findings show that the degree of tracer uptake both in vitro and in vivo is related to the percentage of infiltrating plasma cells which accumulate the tracer in their inner compartments.     

Monitoring the chemotherapeutic response in primary lung cancer using 99mTc-MIBI SPET

Prediction and evaluation of the response to chemotherapy (CTx) are important for the correct and cost-effective treatment of patients with primary lung cancer. Although fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is accepted as the most useful and accurate nuclear medicine technique for this purpose, its expense and limited availability restrict its use. Compared with PET agents, technetium-99m methoxyisobutylisonitrile (MIBI), which is used in nuclear oncology, is cheaper and available in any nuclear medicine clinic. With this in mind, in this study we aimed to evaluate the role of ^99mTc-MIBI in monitoring the chemotherapeutic response in primary lung cancer. Twenty patients with primary lung cancer underwent ^99mTc-MIBI single-photon emission tomography (SPET) at 15 min (early) and 3-4 h (delayed) after injection of the tracer. All patients underwent ^99mTc-MIBI SPET study twice: before and after the 3rd cycle of CTx. Patients were divided into two groups, responders [R(+), n=10] and non-responders [R(-), n=10], according to the change in tumour size on CT scan taken 2 weeks after the last cycle of the CTx. From the SPET images early and delayed tumour/lung ratios (ER and DR) were obtained before and after CTx. In the R(+) group, ER and DR decreased significantly after CTx, from 3.28ǃ.55 to 1.78ǂ.72 (P<0.04) and from 3.23ǃ.55 to 2.0ǂ.88 (P<0.05), respectively. However, in the R(-) group, while ER showed a slight and statistically insignificant increase after CTx (from 2.51ǃ.23 to 2.65ǃ.86), DR increased significantly, from 2.74ǃ.37 to 3.27DŽ.31 (P<0.03). The percentage decreases in ER and DR in the R(+) group after CTx was significantly higher than that in the R(-) group: 34.36%ᆮ.7% vs -13.78%ᆯ.58% (P<0.0002) and 29.45%ᆭ.23% vs -18.58%ᆨ.51% (P<0.0005), respectively. Using a decrease of ⁶% as a threshold for monitoring the chemotherapeutic response, ^99mTc-MIBI had a sensitivity of 90% and a specificity of 100%. We found a positive correlation in 14 patients between ER and DR and survival: r=0.6754 and P=0.008, and r=0.5755 and P=0.031, respectively. Our results suggest that ^99mTc-MIBI might be used in routine practice to monitor the chemotherapeutic response in patients with primary lung cancer, especially when PET is not available.     

Diagnosis of pyogenic pelvic inflammatory diseases by 99mTc-HMPAO leucocyte scintigraphy

Pelvic inflammatory disease (PID) is one of the major health problems of women of child-bearing age. Among the most serious complications of PID is the formation of a tubo-ovarian abscess (TOA). Early diagnosis of this condition may prevent serious surgical complications such as peritonitis and sepsis, which may be fatal. The purpose of this study was to investigate the efficacy of technetium-99m hexamethylpropylene amine oxime (HMPAO) leucocyte scintigraphy in the diagnosis of TOA. Twenty women with high clinical suspicion of TOA underwent ^99mTc-HMPAO leucocyte scintigraphy. The labelling of leucocytes with ^99mTc-HMPAO was performed according to a standard protocol. Scans were obtained at 1, 3 and 24 h following the injection of the labelled leucocytes. In eight cases the early and/or late scan was positive, in 11 cases it was negative, and in one case of ovarian cyst torsion, confirmed by laparoscopy, it showed slight uptake in the capsule of the cyst (false-positive). The sensitivity of ^99mTc-HMPAO leucocyte scintigraphy was 100%, specificity 91.6%, positive predictive value 89%, negative predictive value 100% and overall accuracy 95%. It is concluded that leucocyte scintigraphy is a non-invasive, safe, physiological and accurate procedure for the diagnosis of TOA. The 24-h scan is crucial, since in some cases the abscess was not clearly visualized on the early scan. Leucocyte scintigraphy may reduce the need for CT, diagnostic laparoscopy and unnecessary invasive surgical procedures.     

Non-Q-wave myocardial infarction: impaired myocardial energy metabolism in regions with reduced 99mTc-MIBI accumulation

Reduced regional technetium-99m methoxyisobutylisonitrile (^99mTc-MIBI) accumulation in patients with chronic non-Q-wave infarction (NQWI) but without significant coronary artery stenosis indicates non-transmural damage of the myocardial wall. The aim of this study was to characterise cardiac energy metabolism after NQWI using phosphorus-31 magnetic resonance spectroscopy (³¹P-MRS) and to compare the biochemical remodelling with changes in regional ^99mTc-MIBI uptake and with morphological and functional parameters assessed by magnetic resonance imaging (MRI). Fifteen patients with a history of NQWI, exclusion of significant coronary artery stenosis (<50% diameter stenosis) and hypokinesia of the anterior wall (group A) were examined with ³¹P-MRS to study the effects of NQWI on myocardial energy metabolism. Spectroscopic measurements were performed in the infarct-related myocardial region. Corresponding gradient-echo MR images and myocardial ^99mTc-MIBI single-photon emission tomography images were acquired for exact localisation of the infarct region. All examinations were performed at rest under anti-ischaemic medication. Data were compared with those of patients in whom coronary artery disease had been excluded by angiography (group B, n=10). All patients of group A displayed anterior wall hypokinesia in the infarcted area on both ventriculography and MRI, with a reduced myocardial accumulation of ^99mTc-MIBI (66.3%ᆟ.8% vs 95.6%DŽ.2% in group B). The mean wall thickness during the complete cardiac cycle (9.5ǃ.8 mm vs 13.1ǃ.1 mm in group B, P<0.001), the systolic wall thickening (2.6ǃ.4 mm vs 5.8ǃ.5 mm in group B, P<0.01) and the phosphocreatine/adenosine triphosphate ratio (1.12ǂ.22 vs 1.74ǂ.23 in group B, P<0.01) in the hypokinetic area were all significantly reduced. It is concluded that persisting hypokinetic myocardium after NQWI combined with reduced myocellular uptake of ^99mTc-MIBI displays a reduced PCr/ATP ratio. Our results indicate that morphological remodelling after NQWI is accompanied by fundamental changes in cardiac energy metabolism.     

Imaging macrophages and the apoptosis of granulocytes in a rodent model of subacute and chronic abscesses with radiolabeled monocyte chemotactic peptide-1 and annexin V

Monocytes/macrophages (MJs), the predominant cell types in subacute and chronic inflammation, are attracted to and activated by monocyte chemotactic peptide-1 (MCP-1). MJs promote the resolution of inflammation through the induction of apoptosis and phagocytosis of senescent (spent) and bystander (superfluous) granulocytes. We wished to determine whether MCP-1, which selectively binds to MJs, could be used to image subacute and chronic inflammation. We also sought to image granulocyte apoptosis within these lesions with technetium-99m labeled annexin V, a marker of apoptotic cells. Sterile inflammation was induced in 45 12-week-old male Sprague-Dawley rats by deep intramuscular injection of turpentine into the right thigh. Groups of four to six animals were then imaged 1 h after tail vein injection of 37-148 MBq (1-4 mCi) of ^99mTc-labeled MCP-1 or annexin V 1-14 days after turpentine treatment. Image analysis showed significantly greater activity of both MCP-1 and annexin V in inflamed thighs than in control thighs (165%-290% and 188%-313%, respectively; P<0.01) on days 1-5 after turpentine injection. Dual autoradiography in animals co-injected with iodine-125 labeled bovine serum albumin on days 1 and 4 showed specific location of MCP-1 to infiltrating MJs while annexin V localized to focal zones of apoptosis within granulocytic infiltrates adjacent to abscess cavities. Scintillation well counting on day 5 demonstrated significantly higher (P<0.005) ratios of abscess to control thigh specific activities for MCP-1 (5.83DŽ.17) and annexin V (9.24DŽ.8) as compared to ¹²⁵I-labeled bovine serum albumin (3.11ǂ.65). No significant increases in uptake were noted at imaging or ex vivo analyses on days 13 and 14, when lesions were predominately fibrotic. It is concluded that ^99mTc-labeled MCP-1 and ^99mTc-labeled annexin V both localize in zones of subacute inflammation, reflecting the density of MJs and the incidence of apoptotic granulocytes, respectively. These agents may be useful in the characterization of subacute inflammation.     

Use of myocardial imaging agents for tumour diagnosis – a success story?

The search for new radiopharmaceuticals for tumour diagnosis usually proceeds on the basis of rational concepts drawing on the latest advances in molecular biology. Using this approach, radioactive peptide hormones, antibodies and oligonucleotides have been developed that are used increasingly in nuclear medicine for diagnostic and therapeutic purposes. This article, however, focusses on a group of radiopharmaceuticals whose use in tumour diagnosis was not the outcome of a methodical development programme but rather the result of a chance discovery. These radiopharmaceuticals, thallium-201 and technetium-99m labelled 2-methoxyisobutylisonitrile (MIBI), tetrofosmin and furifosmin, were first developed through extensive research efforts for cardiac imaging, but during their worldwide application for myocardial scintigraphy they were accidentally found to accumulate in tumours. Intensive studies were then begun on cell cultures in an attempt to discover the cause of their uptake into tumours. The aim was to compare the effectiveness of the radiopharmaceuticals for tumour diagnosis in a range of indications and to investigate the various mechanisms by which they are taken up into tumours. While the more favourable radiophysical properties of ^99mTc-MIBI render it superior to ²⁰¹Tl for many diagnostic purposes, neither ^99mTc-tetrofosmin nor ^99mTc-furifosmin has yet proved suitable for clinical routine examinations, although the former has found limited application. In the case of ^99mTc complexes, the breakthrough came with the experimental finding that these substances are substrates of P-glycoprotein, a product of the human multidrug resistance gene (MDR₁). The concentration of ^99mTc complexes in tumour cells is a function of a passive, membrane potential-dependent influx into and a P-glycoprotein-controlled efflux out of the tumour cell. Preliminary studies suggest that in vivo detection of MDR may even be possible. There is also evidence that the P-glycoprotein-mediated transport system can be blocked competitively. However, it will be some time before a system can be developed for detection of MDR on a routine basis.     

Different uptake of 99mTc-ECD and 99mTc-HMPAO in the same brains: analysis by statistical parametric mapping

The purpose of this study was to investigate the differences between technetium-99m ethyl cysteinate dimer (^99mTc-ECD) and technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) uptake in the same brains by means of statistical parametric mapping (SPM) analysis. We examined 20 patients (9 male, 11 female, mean age 62ᆠ years) using ^99mTc-ECD and ^99mTc-HMPAO single-photon emission tomography (SPET) and magnetic resonance imaging (MRI) of the brain less than 7 days after onset of stroke. MRI showed no cortical infarctions. Infarctions in the pons (6 patients) and medulla (1), ischaemic periventricular white matter lesions (13) and lacunar infarction (7) were found on MRI. Split-dose and sequential SPET techniques were used for ^99mTc-ECD and ^99mTc-HMPAO brain SPET, without repositioning of the patient. All of the SPET images were spatially transformed to standard space, smoothed and globally normalized. The differences between the ^99mTc-ECD and ^99mTc-HMPAO SPET images were statistically analysed using statistical parametric mapping (SPM) 96 software. The difference between two groups was considered significant at a threshold of uncorrected P values less than 0.01. Visual analysis showed no hypoperfused areas on either ^99mTc-ECD or ^99mTc-HMPAO SPET images. SPM analysis revealed significantly different uptake of ^99mTc-ECD and ^99mTc-HMPAO in the same brains. On the ^99mTc-ECD SPET images, relatively higher uptake was observed in the frontal, parietal and occipital lobes, in the left superior temporal lobe and in the superior region of the cerebellum. On the ^99mTc-HMPAO SPET images, relatively higher uptake was observed in the medial temporal lobes, thalami, periventricular white matter and brain stem. These differences in uptake of the two tracers in the same brains on SPM analysis suggest that interpretation of cerebral perfusion is possible using SPET with ^99mTc-ECD and ^99mTc-HMPAO.     

99mTc-tetrofosmin SPET in the detection of both primary breast cancer and axillary lymph node metastasis

The aim of this study was to evaluate the usefulness of ^99mTc-tetrofosmin single-photon emission tomography (SPET) in the detection of both primary breast cancer and axillary lymph node metastasis. We studied 192 consecutive patients in whom primary breast cancer was suspected on the basis of mammography and/or physical examination. After intravenous injection of 740 MBq ^99mTc-tetrofosmin, both planar and SPET scintimammography was performed in all patients using a rectangular dual-head gamma camera equipped with low-energy, high-resolution, parallel-hole collimators. In 175 patients with breast cancer at histology, the per-lesion overall sensitivity of SPET and planar imaging for the detection of breast cancer was 95.8% and 75.9% (P<0.0005), respectively. The sensitivity of SPET and planar imaging was, respectively, 96.5% and 79.5% in palpable (P<0.0005) and 90% and 45% in non-palpable lesions (P<0.01). With regard to lesion size, the sensitivity of SPET and planar imaging was, respectively, 90.5% and 45.2% in lesions ⢪ mm (P<0.0005), 95.3% and 81.4% in lesions of 11-20 mm (P<0.005), 100% and 84.6% in lesions of 21-30 mm (P<0.05) and 100% and 95.8% in lesions >30 mm (P>0.05). In the remaining 17 patients with benign mammary lesions at histology, per-lesion overall specificity of SPET and planar imaging was 76.2% and 85.7% (P>0.05), respectively. Neither SPET nor planar imaging showed false-positive results in non-palpable lesions or in those ⢪ mm. In 173 breast cancer patients submitted to axillary lymph node dissection (ALND), per-axilla overall sensitivity of SPET and planar imaging in the detection of axillary lymph node metastasis was 93% and 52.3% (P<0.0005), respectively. The sensitivity of SPET and planar imaging was, respectively, 100% and 82.6% in palpable nodes (P>0.05), 90.5% and 41.3% in non-palpable nodes (P<0.0005), 92.8% and 35.7% in the presence of Г nodes (P<0.0005) and 93.2% and 68.2% in the presence of >3 nodes (P<0.005). The specificity of SPET and planar imaging was 91% and 100% (P<0.05), respectively. ^99mTc-tetrofosmin SPET appears to be a reliable method for the detection of both primary BC and axillary lymph node metastasis, and its diagnostic accuracy exceeds that of ^99mTc-tetrofosmin planar scintimammography. The use of SPET is particularly important in the identification of small non-palpable primary carcinomas and metastatic axillae with Г non-palpable lymph nodes. More extensive use of SPET appears warranted in the management of breast cancer patients.     

99mTc-ECD brain perfusion SPET: variability, asymmetry and effects of age and gender in healthy adults

Reliable and high-resolution reference data for regional cerebral blood flow measured with single-photon emission tomography (SPET) are necessary for optimal clinical and research use. Therefore, a large dataset of normal technetium-99m labelled ethylene cysteine dimer (ECD) perfusion SPET in carefully screened healthy volunteers with an age range spanning six decades was created, with correction for non-uniform attenuation and scatter and based on an anatomically standardised analysis. Eighty-nine healthy volunteers, stratified for gender (46 females, 43 males; age 20-81 years), were included. Twelve volunteers underwent repeated ^99mTc-ECD SPET after 2.5DŽ.3 weeks. An automated whole-brain volume of interest analysis with MANOVA as well as voxelwise analysis using SPM99 was conducted. Average intersubject variability was 4.8% while intrasubject reproducibility was 3.0%. An age-related decline in tracer uptake was found in the anterior cingulate gyrus, bilateral basal ganglia, left prefrontal, left lateral frontal and left superior temporal and insular cortex (all P=0.001-0.02). There was an overall increase in right/left asymmetry with age, which was most pronounced in the frontal and temporal neocortex. The most significant correlations between AI and age decade were found in the prefrontal (R=0.35, P=0.001) and superior temporal neocortex (R=0.43, P<0.001). Women had significantly higher uptake in the right parietal cortex (P<0.001), while men showed higher uptake in the cerebellum and the left anterior temporal and orbitofrontal cortex (all P<0.01). This normative dataset allows age- and gender-specific patient and group assessment of ^99mTc-ECD perfusion SPET under a wide variety of clinical circumstances in relation to normal variations and highlights the importance of both age- and gender-specific normal datasets for optimal analysis sensitivity.     

"FUR" – one size suits all

This work used amalgamated data from previous projects in order to test the concept that when organ function is expressed in terms of tracer kinetics, the results are independent of patient size or gender. Dynamic gamma camera studies were analysed by measuring the rate of movement of tracers from the blood into various organs. These rates were expressed as a "fractional uptake rate" (FUR), which is the fraction of tracer in the blood taken up by the organ per unit time. As these values were small, it was convenient to express the FUR per million seconds. The FUR was calculated using the expression FUR = SLOPE (of Rutland-Patlak plot), multiplied by B(0) (the blood curve value back-extrapolated to time zero), and divided by the TOTAL amount of tracer injected. Data were used from adult patients between the ages of 20 and 49 years who had normal organ function. Organ/tracer groups studied were the skeletal uptake of ^99mTc-MDP, the renal uptake of ^99mTc-MAG3, the renal uptake of ^99mTc-MDP, the renal uptake of ^99mTc-DTPA, the hepatic uptake of ^99mTc-colloid, the splenic uptake of ^99mTc-colloid, and the hepatic uptake of ^99mTc-DISIDA. Each organ/tracer group was divided into three subgroups according to patient size (smallest, middle and largest), and also into subgroups according to gender. Comparison of these subgroups did not show any significant size- or gender-related differences in FUR values. It is concluded that for patients with normally functioning organs the FUR is independent of patient size or gender. Thus, the FUR is a valuable way of expressing organ function, particularly in patients with unusual or rapidly changing body size, such as children.