Pharmacokinetic profile of tamsulosin OCAS

The tamsulosin oral‐controlled absorption system (OCAS®) is a new tablet formulation of the α₁‐adrenoceptor (α₁‐AR) antagonist tamsulosin, which is used for treating lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). The tablet uses the OCAS technology, which was specifically designed to give a more continuous 24‐h release of tamsulosin, resulting in a more consistent and continuous 24‐h plasma concentration, a lower maximum plasma concentration (C_max) and an independence of pharmacokinetics (PKs) on food intake. It was expected that the improved PK profile would translate into a better control of day‐ and night‐time symptoms of BPH and a lower risk of adverse events. Phase I PK studies showed that tamsulosin OCAS indeed has a flattened PK profile with a lower C_max and a more stable and consistent 24‐h concentration of tamsulosin, independent of food intake, compared to conventional tamsulosin. A study combining γ‐scintigraphy and PK analysis of blood samples confirmed that the improved PK profile of tamsulosin OCAS is attributed to the tablet being consistently and continuously released throughout the entire gastrointestinal tract, including the colon.     

Quantitative assessment of technetium-99m methoxyisobutylisonitrile planar perfusion heart studies: application. of multivariate analysis to patient classification

A quantified evaluation of planar cardiac perfusion scintigrams (the objective of the study), obtained using technetium-99m methoxyisobutylisonitrile (MIBI) was performed on the basis of an analysis of circumferential profile curves, representing the perfusion as seen in three typical projections. The analysis involved the curves obtained both at rest and after stress, and was based on a comparison of their shape (trend) with the normal trend (normative evaluation). The latter was obtained by means of an original method of iterative fitting of individual curves into the database. The base consisted of curves recorded in 53 patients (separately in males and females) with normal perfusion of the left ventricle (group I, the reference group). A group of 90 patients suspected of having coronary artery disease (group II) was subdivided into two subgroups on the basis of coronary arteriography: (a) those with and (b) those without critical stenosis of at least one artery. Profile curves characterising the LV perfusion were obtained at rest and after stress. Defects of perfusion were quantified by comparison of individual curves with the normal trends. By means of multivariate analysis it was demonstrated that vectors of mean values characterising the scintigraphically assessed defects of LV perfusion in the two subgroups of group II differed very significantly (P<10^–5). Applying methods of discriminant analysis, a classification of patients from group II was performed into those with probable defects of perfusion and those free of such defects. The sensitivity, specificity and accuracy of diagnosis of coronary ischaemia, based on quantified planar^99mTc-MIBI scintigraphy, reached 86%, 87% and 87%, respectively.     

Pectus excavatum defect on liver-spleen scintigraphy

A 58-year-old man with a pectus excavatum demonstrated a photon-deficient defect within the left lobe of the liver on liver-spleen scintigraphy using Tc-99m SCOL. Computed tomography of the liver clearly revealed the abnormal defect seen on the liver-spleen scan to be due to the pectus excavatum. This case confirms the impression that these skeletal aberrations may cause false-positive hepatic defects.The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense     

Scintigraphic evaluation of myocardial uptake of thallium 201 and technetium 99m pyrophosphate utilizing a rat model of chronic doxorubicin cardiotoxicity

To evaluate the usefulness of myocardial scintigraphy as a monitoring tool for chronic doxorubicin (DXR) cardiotoxicity, a rat model was used to investigate the relationship between the myocardial uptake of thallium 201 (Tl) or rechnetium 99m pyrophosphate (^99mTc-PPi) and histological changes of the heart. Although there was no significant difference in myocardial Tl uptake between control and DXR-treated rats at an early phase after Tl injection, late-phase Tl uptake was significantly higher in the DXR-treated rats than in the control rats, indicating a slow wash-out of Tl from the myocardium. The wash-out rate calculated from scintigraphic examination of DXR-treated rats was significantly decreased with increasing degree of cardiomyopathy. Since the Tl wash-out rate was sharply decreased even in animals with minimal histological changes, it may be a possible monitoring tool for the early detection of chronic DXR cardiotoxicity. On the other hand, myocardial^99mTc-PPi images could be obtained only in rats with severe myocardial changes and hence would not useful for early detection.     

Neuronal dysfunction in heart failure assessed by cardiac 123-iodine metaiodobenzylguanidine scintigraphy

In patients with chronic heart failure, increased sympathetic activity and cardiac sympathetic neuronal dysfunction are present and have been related to unfavourable clinical outcome. Modification of these alterations with the objective to improve prognosis has become an important aim of pharmacological therapy for these patients. A noninvasive technique to assess sympathetic neuronal function at the cardiac level may be valuable in evaluating newly developed therapeutic strategies. 123-iodine metaiodobenzylguanidine can be used visualize cardiac sympathetic nerve function and activity. Single photon emission computerized tomographic is preferred to planar scintigraphy since it does not depend on superposition of other anatomical structures and may allow assessment of regional cardiac 123-iodine metaiodobenzylguanidine uptake. Although the quantitation of cardiac uptake in these tomographic images has several limitations, the use of the left ventricular cavity as a reference, calibrated by the 123-iodine activity in a blood sample drawn at the time of acquisition, may have clinical applications, with respect to the evaluation of therapeutical intervention in patients with heart failure.Abbreviations BS blood sample - CD count density - dP/dt change in pressure over time - [¹²³I] 123-iodine - K_m affinity constant - MIBG metaiodobenzylguanidine - MB_q mega Bequerel - SPECT single photon emission computerized tomography - V_m capacity constant     

Cardiac MIBG scintigraphy is a sensitive tool for detecting cardiac sympathetic denervation in Parkinson's disease.

[(123)I]Metaiodobenzylguanidine ([(123)I]MIBG) cardiac scintigraphy could be helpful to differentiate Parkinson's disease (PD) from multiple system atrophy (MSA), demonstrating that, in PD with autonomic failure but not in MSA, there is a myocardial postganglionic sympathetic dysfunction. To investigate whether this method is more sensitive than standard autonomic testing to detect early involvement of sympathetic cardiac efferent, we analyse MIBG myocardial uptake in 8 PD patients with normal autonomic testing (nondysautonomia PD group, NDPD) in comparison with 10 PD patients with abnormal autonomic testing (dysautonomia PD group, DPD) and 10 MSA patients. Global MIBG uptake was assessed using the ratio of [(123)I]MIBG uptake in the heart to the upper mediastinum (H/M) on planar scintigraphic data. Regional MIBG uptake was determined on two single photon emission tomography scans in regions of the left ventricle. The mean H/M ratios were significantly different among the three groups (P < 0.0001). H/M ratios of both NDPD and DPD patients groups (H/M = 1.83 +/- 0.50 and 1.24 +/- 0.40, respectively) were significantly lower than in MSA patients (H/M = 2.52 +/- 0.60). However, in NDPD patients, H/M was significantly higher than in DPD patients. When compared to MSA patients, NDPD patients showed a regional reduction in MIBG uptake in all left ventricle regions markedly in the apex and the inferior wall. Our results suggest that MIBG myocardial scintigraphy (analysis of both H/M ratio and regional MIBG uptake) may be more sensitive than standard autonomic testing for the early detection of silent autonomic dysfunction in PD.     

Hepatobiliary scintigraphy in a patient with bilhemia

A 4-year-old child referred for acute jaundice following percutaneous needle biopsy of the liver underwent hepatobiliary scintigraphy. Although all conventional liver tests suggested preservation of hepatocyte function, the tracer uptake in the liver appeared dramatically reduced at scintigraphy and the blood pool activity did not decrease significantly until the end of the study. Visualization of the bile ducts indicated, however, that the tracer was taken up by the hepatocyte and further excreted into the biliary tree. There was no tracer pooling in the biliary tree although no bowel activity was observed, even on delayed images. The association of persistent blood pool activity, bile duct visualization without tracer pooling, and nonvisualization of the bowel was caused by a continuous recirculation of the tracer from the biliary tree into the bloodstream. The presence of a biliovenous fistula was further proven by percutaneous transhepatic cholangiography performed 24 h later. Since 1975, only 16 cases of bilhemia have been reported. To the best of our knowledge the scintigraphic pattern of this rare but lifethreatening complication has not previously been reported.     

Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases. Received 14 April and in revised form 5 July 1997     

The value of pretreatment clinical and biochemical parameters in patients with newly diagnosed untreated prostate carcinoma and no indications for bone metastases on the bone scintigram

Between 10% and 25% of patients with newly diagnosed prostate cancer without bone metastases at the time of diagnosis will develop metastases during follow-up. To determine the value of clinical and biochemical parameters for assessment of prognosis at the time of diagnosis, a retrospective study was performed in 124 consecutive patients with newly diagnosed prostate cancer without bone metastases. The mean follow-up was 41 months, during which time 36 patients died and 15 patients developed metastases. Bone scans were classified from 0 (=normal) through 2 (=abnormal, but not typical for metastases) and were correlated with age, alkaline phosphatase (AP), prostate-specific antigen (PSA), tumour grade, T-stage and N-stage. In patients with a class 2 scan, additional roentgenograms and follow-up were used to exclude metastases at initial stage. All parameters, including therapy, were finally correlated with the development of metastases and survival. For survival 38 patients with proven metastases were used as controls. For all parameters tested, no statistically significant differences were found between the three bone scan classifications. The interval between diagnosis and the development of metastases ranged from 12 to 72 months. For the risk of development of metastases only PSA was found to be a significant correlate (P=0.0075). However, when tumour stages were clustered in limited disease (T0–2) and extensive disease (T3–4), the incidence of metastases was significantly higher in patients with extensive disease than in those with limited disease (P=0.0021). Finally, age, PSA and Anderson classification were found to be significant correlates of survival, but in stepwise analysis PSA was selected as the most prognostic variable (P<0.0001). In contrast with a typical pattern of metastases on bone scintigraphy, an abnormal scan (class 1 and 2) at the time of diagnosis is not a poor prognostic parameter of the risk of death. In conclusion, in patients with prostate cancer without bone metastases at the time of diagnosis, pretreatment PSA and tumour stage can be used for the assessment of risk of development of metastases during follow-up and survival. For this purpose, tumour stage should be clustered in limited and extensive disease. Received 14 April and in revised form 9 June 1997