The threshold level of urinary cadmium associated with increased urinary excretion of retinol-binding protein and beta 2-microglobulin: a re-assessment in a large cohort of nickel-cadmium battery workers.

OBJECTIVE: To evaluate the threshold value of urinary cadmium (CdU) for renal dysfunction on the basis of relationships unconfounded by protein degradation, diuresis and the renal effects associated with chronic smoking. Methods We studied 599 workers (451 men, mean age 45.4 years) who were employed in four nickel-cadmium battery plants for 18.8 years on average. After adjustment for covariates by multiple regression, the CdU threshold values for increased concentrations of retinol-binding protein (RBPU) and b(2)-microglobulin (b(2)-mU) were assessed by logistic regression and benchmark dose analyses using as referents workers with CdU<1 µg/g creatinine. Results Relationships between urinary proteins and CdU (µg/g creatinine) were influenced by sex, age, diuresis and especially smoking. When considering all workers, odds for abnormal RBPU and b(2)-mU were significantly increased from CdU of 6-10 and >10, respectively. The benchmark dose (BMD5) and the benchmark dose lower limit (BMDL5) for a 5% excess in the background prevalence of abnormal RBPU and b(2)-mU were estimated at 5.1/3.0 and 9.6/5.9. When excluding ever smokers, odds for abnormal RBPU and b(2)-mU were both increased only among workers with CdU>10 (OR, 21.8, 95% CI, 6.4-74.4 and OR, 15.1, 95% CI, 3.6-63.1, respectively). In never smokers, these BMD5/BMDL5 of CdU were estimated at 12.6/6.6 and 12.2/5.5 while in ever smokers they were 6.2/4.9 and 4.3/3.5. Conclusions On the basis of associations undistorted by smoking and adjusted for covariates, the BMDL5 of CdU for low-molecular-weight proteinuria induced by occupational exposure to Cd can be reliably estimated between 5.5 and 6.6 µg/g creatinine.

Early prediction of endocrine therapy effect in advanced breast cancer patients using 99mTc-depreotide scintigraphy.

UNLABELLED: In vitro assessment of hormone receptor status using a ligand-binding assay or immunohistochemistry in breast cancer patients predicts endocrine responsiveness with an accuracy of only 60%-70%. Assessment of an end product of estrogen receptor stimulation, such as the progesterone receptor, is assumed to provide a measure of functional receptor content and has proven to increase predictive accuracy. In analogy with the estrogen-dependent regulation of somatostatin receptor (SSTR) expression in endocrine-responsive human breast cancer cell lines, efficient antiestrogen treatment in patients may result in a downregulation of SSTR at the cell surface in breast tumors. In vivo imaging of this molecular event by means of sequential (99m)Tc-depreotide scintigraphy could enable selection of breast cancer patients susceptible to endocrine therapy. METHODS: Twenty patients with a diagnosis of advanced breast cancer in whom first- or second-line hormonal therapy was going to be initiated were included. Patients underwent sequential (99m)Tc-depreotide scintigraphy before and 3 wk after initiating hormonal treatment. Follow-up data were retrieved from routine clinical evaluation by means of physical examination, imaging (e.g., bone scan, CT, MRI) and blood analysis. Lesion-to-background ratios (L/BGs) were calculated on planar and SPECT images and a change of >25% between the baseline and follow-up scan was considered significant. RESULTS: At 6 mo after initiation of treatment, 8 patients had stable disease and were considered to be responding to hormonal treatment, whereas 10 patients had progressive disease and were considered to be nonresponders. The positive and negative predictive values of baseline (99m)Tc-depreotide scintigraphy for endocrine responsiveness were 73% (8/11) and 100% (7/7), respectively. Sequential scans were always both positive or both negative. The relative change in (99m)Tc-depreotide uptake between sequential scans significantly differed in responders compared with nonresponders (P= 0.017)-uptake decreased in the first group and increased in the latter. As such, baseline (99m)Tc-depreotide scintigraphy combined with the changes in tracer uptake between the baseline and follow-up scan predicted endocrine responsiveness with an accuracy of 100%. CONCLUSION: Sequential (99m)Tc-depreotide scintigraphy could allow for separation of responders and nonresponders immediately or as early as 3 wk after initiation of treatment.

99mTc depreotide scan compared with 99mTc-MDP bone scintigraphy for the detection of bone metastases and prediction of response to hormonal treatment in patients with breast cancer.

BACKGROUND: The purpose of this study was to determine the potential role of Tc depreotide scintigraphy for the evaluation of bone metastases compared with Tc methylenediphosphonate (MDP) bone scintigraphy and for the prediction of treatment response in breast cancer patients in whom first- or second-line hormonal therapy was to be initiated. METHODS: Twelve patients with a diagnosis of advanced breast cancer were included. All patients underwent both a bone scan and a depreotide scan and at least one other conventional imaging procedure, including plain film radiography (n=11), computed tomography (n=6) or magnetic resonance imaging (n=5), for confirmation of metastatic disease. The mean time interval between the bone scan and the depreotide scan was 30.6 days. Follow-up data were retrieved from routine clinical evaluation by means of physical examination, imaging and blood analysis. RESULTS: On a patient basis we found a sensitivity, specificity and accuracy of, respectively 100%, 50% and 83.3% for the bone scan and 62.5%, 100% and 75% for the depreotide scan in the diagnosis of bone metastasis. In eight patients with available follow-up data two with a positive depreotide scan remained stable and five of six patients with a negative depreotide scan had progressive disease. CONCLUSION: In this small series of breast cancer patients Tc depreotide scintigraphy proves less sensitive but more specific as compared to Tc-MDP bone scintigraphy in measuring the extent of bone metastasis. On the other hand Tc depreotide scintigraphy elucidates, non-invasively, tumour characteristics and may be indicative for prognosis and response to hormonal treatment.

99mTc-ciprofloxacin planar and tomographic imaging for the diagnosis of infection in the postoperative spine: experience in 48 patients.

The non-invasive assessment of postoperative spinal infections can pose a substantial diagnostic challenge, especially in the presence of orthopaedic devices. Whereas white blood cell scanning is of limited use in the spine, the low normal bone marrow uptake of technetium-99m ciprofloxacin combined with its claimed bacterial specificity makes it theoretically an ideal candidate for the evaluation of postoperative spinal infections. This study aimed to evaluate 99mTc-ciprofloxacin planar and single-photon emission tomography (SPET) imaging in relation to microbiological and clinical diagnosis in the postoperative spine. Planar imaging was performed at 1, 3 and 24 h and SPET was performed at 3 h post injection of 370 MBq 99mTc-ciprofloxacin. Images were scored by two independent certified nuclear medicine physicians, blinded to the final diagnosis. Within the 48 patients, there were 13 deep infections. Sensitivity, specificity and accuracy at visual scoring were respectively 54%, 71% and 67% (1 h), 62%, 77% and 73% (3 h), 42%, 91% and 77% (24 h) for planar imaging and 100%, 74% and 81% for SPET. When recently operated patients (< 6 months) were excluded, the specificity of the SPET imaging rose to 81%. In conclusion, unlike white blood cell scanning, 99mTc-ciprofloxacin SPET is sensitive in evaluating infections in the postoperative spine. Sensitivity is much higher for SPET than for planar imaging. However, the results presented prove that its specificity is limited, especially in recently operated patients. Taking this limitation into account, we advise planar and SPET imaging at 3 h post injection and an interval of at least 6 months after surgery to minimise the likelihood of false positives.

99mTc ciprofloxacin imaging for the diagnosis of infection in the postoperative spine.

BACKGROUND: The non-invasive assessment of postoperative spinal infections can pose a substantial diagnostic challenge, especially in the presence of orthopaedic devices. In contrast to white blood cell scanning, which is of limited use in the spine, the low uptake of 99mTc ciprofloxacin into normal bone marrow, combined with its claimed bacterial specificity, makes it, theoretically, an ideal candidate for evaluating postoperative spinal infections. AIM: This study aimed to evaluate 99mTc ciprofloxacin planar and single photon emission tomography (SPET) imaging in relation to microbiological diagnosis in the postoperative spine. METHODS: Only patients with a microbiologically confirmed diagnosis were included in this analysis. Planar imaging was performed at 1, 3 and 24 h, and SPET was performed at 3 h post-injection of 370 MBq 99mTc ciprofloxacin. Images were scored by two independent, certified, nuclear medicine physicians, blinded for the final diagnosis. RESULTS: Within the first 22 consecutive patients with microbiological diagnosis, there were nine deep infections. Sensitivity, specificity and accuracy at visual scoring were, respectively, 67%, 77%, 73% (1 h), 78%, 69%, 73% (3 h), and 56%, 92%, 77% (24 h) for planar imaging, and 100%, 54%, and 73% for SPET. CONCLUSION: In contrast to white blood cell scanning, SPET with Tc ciprofloxacin is sensitive in evaluating infections in the postoperative spine. Sensitivity is higher for SPET than for planar imaging. However, the results presented prove that its specificity is limited, especially in patients who have recently (< 6 months) undergone surgery. Taken this limitation into account, we advise planar and SPET imaging at 3 h post-injection and at an interval of at least 6 months after surgery to minimize the chance for false positives.

18-Fluorine fluorodeoxyglucose positron emission tomography for the diagnosis of infection in the postoperative spine.

BACKGROUND: Using conventional imaging methods, including magnetic resonance imaging and labeled leukocyte scanning, the diagnosis of infection in the postoperative spine remains a diagnostic challenge. Recently, promising results have been reported using 18F-fluorodeoxyglucose positron emission tomography for various infectious problems. This study aimed to investigate the value of 18F-fluorodeoxyglucose positron emission tomography in patients suspected of having spinal infection after previous surgery of the spine. METHODS: Fifty-seven consecutive patients with a history of previous spinal surgery were prospectively included between February 1999 and June 2001. 18F-fluorodeoxyglucose positron emission tomography was performed 60 to 90 minutes after injection of 370 MBq 18F-fluorodeoxyglucose. Images were scored visually and semiquantitatively by two blinded, independent, certified nuclear medicine physicians, experienced with positron emission tomography. Differences were assessed by consensus. Results were correlated with final diagnosis allowing calculation of sensitivity, specificity and accuracy. Receiver operating characteristic analysis was performed to find optimal cut-off values. RESULTS: Fifteen patients had spinal infection. Using the most sensitive cut-off values sensitivity, specificity and accuracy were 100%, 81%, and 86%, respectively, for both visual and semiquantitative scoring. In the group without metallic implants (n = 27), false positives (n = 2) only occurred in the first 6 months after surgery. In the group with metallic implants (n = 30), false positives (n = 6) were not confined to recently operated patients. CONCLUSIONS: Overall accuracy was excellent (86%) with a negative predictive value of 100%. 18F-fluorodeoxyglucose positron emission tomography holds promise to become the standard imaging technique in this difficult patient population, as it is straightforward, provides a rapid result (2 hours) and because accurate alternatives are lacking.

Biological imaging for the diagnosis of inflammatory conditions.

Radiopharmaceuticals used for in vivo imaging of inflammatory conditions can be conveniently classified into six categories according to the different phases in which the inflammatory process develops. The trigger of an inflammatory process is a pathogenic insult (phase I) that causes activation of endothelial cells (phase II); there is then an increase of vascular permeability followed by tissue oedema (phase III). Phase IV is characterised by infiltration of polymorphonuclear cells, and a self-limiting regulatory process called apoptosis is observed (phase V). If the inflammatory process persists, late chronic inflammation takes place (phase VI). In some pathological conditions, such as organ-specific autoimmune diseases, chronic inflammation is present early in the disease. The aim of nuclear medicine in the field of inflammation/infection is to develop noninvasive tools for the in vivo detection of specific cells and tissues. This would allow early diagnosis of initial pathophysiological changes that are undetectable by clinical examination or by other diagnostic tools, and could also be used to evaluate the state of activity of the disease during therapy. These potential applications are of great interest in clinical practice. In this review, we describe the various approaches that have been developed in the last 25 years of experience. Recent advances in the diagnosis of inflammatory processes have led to the development of specific radiopharmaceuticals that are intended to allow specific stage-related diagnosis.

18 F-Fluorodeoxyglucose triple-headed coincidence detection imaging in oncology: preliminary results and comparison with dedicated PET.

BACKGROUND: Dual head coincidence (DHC) imaging has been proposed as a valuable and cheaper alternative to oncological PET. The increased sensitivity of the recently-developed triple-headed gamma camera (THC) optimized for coincidence detection has not been either validated or compared to the sensitivity of a dedicated PET system in a clinical study. MATERIAL/METHODS: Differences in contrast-to-noise-ratio (CNR) between dedicated FDG PET, DHC and THC imaging were assessed using a hot sphere phantom. Twenty-two oncological patients were prospectively studied with consecutive whole body FDG PET and FDG THC imaging. The images were visually read by 2 experienced nuclear medicine specialists. The diagnostic sensitivity of FDG THC imaging was assessed using FDG PET as the imaging gold standard. Lesion size was determined using computed tomography or magnetic resonance imaging. RESULTS: The mean gain in CNR for THC as compared to DHC imaging was 35% (10-56%). Of 63 lesions, 58 (92%) on FDG PET were also detected with THC imaging. Considering only lesions smaller than 15 mm, the relative sensitivity was 86% (24/29). All lesions above 15 mm (n=34) were detected using THC imaging. CONCLUSIONS: The first clinical results for THC imaging are promising. The overall relative sensitivity in this limited series was 92%. Only a few lesions smaller than 15 mm were missed.