Dose selection for radioiodine therapy of borderline hyperthyroid patients with multifocal and disseminated autonomy on the basis of 99mTc-pertechnetate thyroid uptake

The aim of this study was to optimise radioiodine therapy of diffuse and nodular toxic goitre by calculation of the radiation dose delivered to the thyroid on the basis of the pretreatment technetium-99m pertechnetate thyroid uptake under thyrotropin suppression (TcTU(s)). The TcTU(s) value serves as a substitute for the non-suppressible iodine turnover and the functional autonomous mass. Marinelli's formula was used to calculate tissue absorbed doses of 150 Gy, 200 Gy, 250 Gy and 300 Gy to the thyroids of 438 patients with multifocal and disseminated autonomy. The mean age of patients was 70+/-9 years, and the mean thyroid volume was 54+/-26 ml. Two hundred and sixty-one of the patients had at least one documented previous episode of overt hyperthyroidism. Tissue absorbed doses were adapted to the pretreatment TcTU(s): 150 Gy for a TcTU(s) of 1.5%-2.49%, 200 Gy for a TcTU(s) of 2.5%-3.49%, 250 Gy for a TcTU(s) of 3.5%-4.49% and 300 Gy for a TcTU(s) of > or =4.5%. Normalisation of TcTU(s) and thyrotropin (TSH), thyroid volume reduction and frequency of hypothyroidism and recurrent hyperthyroidism were evaluated 1 year after a single radioiodine therapy. The presented dose strategy resulted in normalisation of TcTU(s) in 96% and an increase in TSH to the normal range in 92%. Recurrent hyperthyroidism was observed in only five patients. Thyroid volume decreased from 54+/-26 before treatment to 34+/-20 ml, a mean reduction of 37%. The frequency of hypothyroidism, at 0.9%, was encouragingly low. Dose selection in accordance with pretreatment TcTU(s) can be recommended for elimination of functional autonomous tissue with a single radioiodine therapy in patients of advanced age with enlarged thyroid glands and relevant autonomous masses who are at risk of developing iodine-induced hyperthyroidism.     

99mTcO(BAT-NI), a novel nitroimidazole tracer: in vivo uptake studies in ischaemic myocardium

Myocardial perfusion single-photon emission tomography (SPET) performed with cationic technetium-99m complexes indicates ischaemic areas as cold lesions. By contrast, nitroimidazole derivatives labelled with fluorine-18 or (99m)Tc have recently shown promising results for hot spot imaging of ischaemic myocardium. This study evaluates (99m)TcO(BAT-NI), a new (99m)Tc complex comprising the nitroimidazole ligand, 2,10-dimercapto-2,10-dimethyl-4,8-diaza-6-[4-(2-nitroimidazolyl)butyl]undecane, in a low-flow in vivo model of myocardial ischaemia in thoracotomised rats. To elucidate the influence of the 2-nitroimidazole group on ischaemia-induced uptake, comparisons with ligand derivatives were performed where (a) the 2-nitro group was deleted [(99m)TcO(BAT-I)], (b) the 2-nitroimidazole functionality was replaced by a Br atom [(99m)TcO(BAT-Br)] and (c) the (99m)TcO(BAT) moiety was replaced by an iodine-125 iodophenoxybutyl ligand ((125)IP-NI). The radiolabelled compounds were i.v. injected 15 min after reducing resting myocardial blood flow by 50-60% and the uptake of radioactivity was assessed 90 min post injection. Autoradiography of left ventricular short-axis slices showed median uptake ratios of ischaemic/non-ischaemic myocardium (I/N) of 3.4, 4.5 and 3.4 for (99m)TcO(BAT-NI), (99m)TcO(BAT-I) and (99m)TcO(BAT-Br), respectively. In contrast, (125)IP-NI was not preferentially taken up by ischaemic myocardium. Accumulation of (99m)TcO(BAT-NI) in ischaemic heart regions was comparable to that in the liver. Biodistribution studies showed a median uptake of 0.65% ID/g of (99m)TcO(BAT-NI) in ischaemic tissue and an I/N of 3.3. On planar images of the thorax and upper abdomen the ischaemic hearts were visualised faintly; the median heart to lung count ratio for (99m)TcO(BAT-NI) was 1.7, and the median heart to liver count ratio was 1.0. We conclude that uptake of (99m)TcO(BAT-NI) in ischaemic myocardium does not depend on the nitroimidazole moiety but is intrinsic to the BAT complex. Clinical use of the (99m)TcO(BAT)-labelled tracers seems unlikely owing to their low uptake and their low ischaemic tissue contrast on planar images in vivo.     

99mTc-sestamibi thyroid uptake in euthyroid individuals and in patients with autoimmune thyroid disease

Purpose We investigated the biokinetics of ^99mTc-sestamibi in the thyroid of euthyroid volunteers (EVs) and in patients with autoimmune thyroid diseases and determined the best time interval between ^99mTc-sestamibi injection and calculation of uptake.Methods Forty EVs, 30 patients with Graves disease (GD), 15 patients with atrophic Hashimotos thyroiditis (AHT) and 15 patients with hypertrophic Hashimotos thyroiditis (HHT) underwent ^99mTc-sestamibi thyroid scintigraphy. Dynamic images were acquired for 20 min, and static images were obtained 20 min, 60 min and 120 min post injection. Five-, 20-, 60- and 120-min uptake, time to maximal uptake (T_max) and T_1/2 of tracer clearance were calculated. Thyroid hormones and antibodies were measured. ^99mTc-pertechnetate uptake was investigated in GD patients.Results T_max was approximately 5 min in all four groups. The mean T_1/2 value for EVs was similar to the GD value and lower than the HHT and AHT values. The mean (±SD) 5-min uptake was 0.13% (±0.05%) for EVs. The 5-min uptake in GD was higher than that in EVs(P<0.001) and correlated with free thyroxine (r=0.54) and with ^99mTc-pertechnetate uptake (r=0.68). Uptake in HHT was higher than that in AHT (P=0.0003) and EVs (P=0.002). Uptake in AHT was lower than uptake in EVs (P=0.0001).Conclusion Five minutes is the optimal time interval between ^99mTc-sestamibi injection and calculation of thyroid uptake. Five-minute uptake differentiates euthyroid individuals from GD patients. There is a high correlation between ^99mTc-sestamibi and ^99mTc-pertechnetate uptake in GD. The reduced ^99mTc-sestamibi uptake in AHT patients is probably due to glandular destruction and fibrosis. Inflammatory infiltrate and high mitochondrial density in thyrocytes possibly explain the increased uptake in GD and HHT.     

Establishment of radioactive astatine and iodine uptake in cancer cell lines expressing the human sodium/iodide symporter

The sodium/iodide symporter (NIS) has been recognized as an attractive target for radioiodine-mediated cancer gene therapy. In this study we investigated the role of human NIS for cellular uptake of the high LET alpha-emitter astatine-211 ((211)At) in comparison with radioiodine as a potential radionuclide for future applications. A mammalian NIS expression vector was constructed and used to generate six stable NIS-expressing cancer cell lines (three derived from thyroid carcinoma, two from colon carcinoma, one from glioblastoma). Compared with the respective control cell lines, steady state radionuclide uptake of NIS-expressing cell lines increased up to 350-fold for iodine-123 ((123)I), 340-fold for technetium-99m pertechnetate ((99m)TcO(4)(-)) and 60-fold for (211)At. Cellular (211)At accumulation was found to be dependent on extracellular Na(+) ions and displayed a similar sensitivity towards sodium perchlorate inhibition as radioiodide and (99m)TcO(4)(-) uptake. Heterologous competition with unlabelled NaI decreased NIS-mediated (211)At uptake to levels of NIS-negative control cells. Following uptake both radioiodide and (211)At were rapidly (apparent t(1/2) 3-15 min) released by the cells as determined by wash-out experiments. Data of scintigraphic tumour imaging in a xenograft nude mice model of transplanted NIS-modified thyroid cells indicated that radionuclide uptake in NIS-expressing tumours was up to 70 times ((123)I), 25 times ((99m)TcO(4)(-)) and 10 times ((211)At) higher than in control tumours or normal tissues except stomach (3-5 times) and thyroid gland (5-10 times). Thirty-four percent and 14% of the administered activity of (123)I and (211)At, respectively, was found in NIS tumours by region of interest analysis ( n=2). Compared with cell culture experiments, the effective half-life in vivo was greatly prolonged (6.5 h for (123)I, 5.2 h for (211)At) and preliminary dosimetric calculations indicate high tumour absorbed doses (3.5 Gy/MBq(tumour) for (131)I and 50.3 Gy/MBq(tumour) for (211)At). In conclusion, NIS-expressing tumour cell lines of different origin displayed specific radionuclide uptake in vitro and in vivo. We provide first direct evidence that the high-energy alpha-emitter (211)At is efficiently transported by NIS. Application of (211)At may direct higher radiation doses to experimental tumours than those calculated for (131)I. Thus, (211)At may represent a promising alternative radionuclide for future NIS-based tumour therapy.     

Incremental diagnostic value of preoperative 99mTc-MIBI SPECT in patients with a parathyroid adenoma.

The purpose of this prospective study was to evaluate the diagnostic value of early parathyroid SPECT combined with quantitative analysis as compared with planar imaging in patients undergoing minimally invasive radioguided surgery. METHODS: A total of 52 consecutive patients with primary hyperparathyroidism underwent planar and SPECT parathyroid scintigraphy 2-5 d before surgery. Each patient had a single-tracer dual-phase technique using (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) and a double-tracer subtraction technique using a delayed (99m)Tc-pertechnetate scan. Immediately after the first (99m)Tc-MIBI planar image, a SPECT study was acquired. Before radioguided parathyroidectomy, each patient was reinjected with (99m)Tc-MIBI. Serum calcium levels were available for all patents before surgery and at 8 and 24 h after surgery. Serum parathyroid hormone (PTH) levels were also available for all patients. Quantitative analysis was performed using the average count ratio of parathyroid to left thyroid lobe, right thyroid lobe, and maximum thyroid activity. All patients had histopathologic examination of the removed glands. RESULTS: The average time for radioguided surgery was 30 min (range, 20-40 min). Postsurgical calcium levels correlated significantly with the adenoma weight (r = 0.5; P = 0.016). Combined planar scintigraphy correctly identified 41 adenomas (79%). SPECT increased the sensitivity to 96%. SPECT was superior to planar imaging in 9 patients, mainly in patients with ectopic adenomas or with multinodular goiters. Gland size did not affect significantly the detectability of SPECT. (99m)Tc-MIBI retention was noted in only 31 adenomas (60%). The average uptake ratios of parathyroid counts to the left lobe, right lobe, and maximum thyroid activity were 1.20 +/- 0.42, 1.29 +/- 0.45, and 0.84 +/- 0.35, respectively. The latter ratio was significantly correlated with PTH levels before surgery (r = 0.408; P = 0.04). CONCLUSION: Our data indicate that early preoperative SPECT in patients with primary hyperparathyroidism is essential for accurate localization of parathyroid adenomas and for the selection of patients who are candidates for minimally invasive radioguided surgery. Planar parathyroid imaging is less sensitive compared with SPECT, and washout kinetics of (99m)Tc-MIBI are unreliable in the dual-phase technique. Patients with higher presurgical PTH levels may especially benefit from radioguided surgery.     

Technetium-99m-MRP20, a potential brain perfusion agent: in vivo biodistribution and SPECT studies in non-primate animals

MRP20 (N-(2(1H pyrolylmethyl]N'-(4-pentene-3-one-2] ethane-1,2-diamine) complexes with technetium-99m, yielding a neutral, lipophilic species. This compound has been characterized as [TcO(MRP20)]. Biologic investigation of [99mTc][TcO(MRP20)] in female rats showed 2.35% ID in the brain 30 min p.i. with no significant wash-out over 3 hr. A single-photon emission computed tomography (SPECT) study in a dog demonstrated rapid tracer uptake in the brain, reaching a maximum within 1 min, with 2.24% i.d. 15 min p.i., decreasing to 1.7% after 4 hr. The complex undergoes hydrolysis in vitro forming a cationic species. This is possibly the trapping mechanism in the brain in vivo. The main excretory route of [99mTc][TcO(MRP20)] is via the hepatobiliary tract. There is evidence of some "in vivo" cell labeling and soft-tissue uptake.     

Scintigraphic patterns in patients with subclinical hyperthyroidism

The occurrence of suppressed thyroid stimulating hormone (TSH) levels in the presence of normal free thyroxine (fT4) and free triiodothyronine (fT3) is not rare. Although this entity may be defined as "subclinical hyperthyroidism", many patients presented with the above laboratory findings, suffer from non-specific signs and symptoms that could be related to hyperthyroidism. The aim of this study was to evaluate this entity using the standard method of radionuclide thyroid imaging by (99m)Tc-pertechnetate ((99m)TcO(4)(-)). Fifty-two patients (18 males; mean age: 45+/-9 years and 34 females; mean age: 43+/-11 years) with suppressed serum TSH levels and normal fT3 and fT4 levels, who were referred to our nuclear medicine department for thyroid scintigraphy were prospectively included in the study. Any thyroidal or non-thyroidal medication, thyroid surgery or non-thyroidal diseases constituted the main exclusion criteria. Thyroid scintigraphy was performed 15 min after the i.v. injection of 111 MBq (99m)TcO(4)(-) using a pinhole collimator. Scintigraphic findings were visually evaluated. All patients had normal serum levels of fT4 (mean value 1.53+/-0.14 ng/dl, normal range: 0.89-1.8 ng/dl) and fT3 (mean value 3.9+/-0.17 ng/dl, normal range: 2.3-4.2 ng/dl). Mean value of serum TSH levels was 0.09+/-0.12 microIU/ml (normal range: 0.35-5.5 microIU/ml). The above hormones were tested by the chemiluminescent method. Patients showed seven different scintigraphic patterns in their thyroid scintigrams as follows: hyperactive+hypoactive multinodular goiters, 27%; hyperactive multinodular goiters, 23%; hypoactive multinodular goiters, 15%; solitary hypoactive nodular glands, 14%; normal glands, 9%; solitary hyperactive nodular glands, 8%; and diffuse hyperactive glands, 4%. All but two patients (50/52 = 96%) showed mild to moderate hyperplasia of the thyroid gland. It is concluded that most patients with subclinical hyperthyroidism, (96%) show mild to moderate hyperplasia of the thyroid, and many (65%) show multinodularity with at least one hyperactive nodule.     

Clearance of Tc-99m DTPA aerosol in mismatched and matched pulmonary perfusion defects

PURPOSE: To evaluate clearance changes of Tc-99m DTPA aerosol in mismatched and matched pulmonary perfusion defects. MATERIALS AND METHODS: Twenty-one patients (14 women, 7 men; mean age, 51 +/- 14 years) with possible pulmonary embolism were included in the study. On the day after perfusion (Q) scintigraphy with 5 mCi Tc-99m MAA, radioaerosol inhalation scintigraphy was performed using 45 mCi Tc-99m DTPA. Immediately and 45 minutes after the inhalation, early and delayed inhalation images (EI and DI, respectively) were obtained. Group 1 included 11 patients with mismatched defects who had a high probability of pulmonary embolism according to the Q/EI scan results. Group 2 included 10 patients with matched defects who had a low probability of PE. Contralateral normal lungs of 7 patients in group 2 served as controls (group 3). In groups 1 and 2, regions of interest were drawn over the mismatched and matched perfusion defects where they were best visualized, and this region of interest was mirrored to the same region on EI and DI images. For the control group, this was done in the contralateral normal lung. Mean counts in each region of interest were used for quantitative analysis, and the percentage clearance ratio was calculated using the following formula: early counts - late counts/early counts x 100. RESULTS: The average percentage clearances for the three groups were as follows: group 1, 37% +/- 10%; group 2, 21% +/- 4%; group 3, 24% +/- 7%. Differences between groups 1 and 3 were significant, as were those between groups 1 and 2 (P < 0.05). Patients with mismatched perfusion defects had increased DTPA clearance compared with the control group and those with matched defects. CONCLUSIONS: Vascular occlusion may lead to impairment of the alveolar-capillary barrier and consequently an increase in the clearance of Tc-99m DTPA aerosol in embolized regions. Immediately after inhalation, Tc-99m DTPA imaging should be started in the projection where perfusion defects are best seen to avoid potential misinterpretation of pulmonary embolism.     

Embolic distribution through patent foramen ovale demonstrated by (99m)Tc-MAA brain SPECT after Valsalva radionuclide venography.

Cryptogenic stroke might relate to paradoxical embolism stemming from right-to-left shunt caused by patent foramen ovale (PFO). We performed radionuclide venography using the Valsalva maneuver, followed by (99m)Tc-macroaggregated albumin (MAA) brain SPECT to investigate the fate of emboli originating from the lower extremities. METHODS: Ten patients (9 men, 1 woman; mean age, 61 +/- 17 y) with PFO underwent radionuclide venography with and without the Valsalva maneuver on the whole-body image, followed by brain SPECT with (99m)Tc-MAA to determine the cortical uptake that would detect right-to-left shunt. After counts in each region of interest (ROI) were normalized by comparison with the averaged count, the distribution of MAA was compared with that of (99m)Tc-hexamethyl-propyleneamine oxime (HMPAO) brain SPECT by drawing ROIs on frontal, temporoparietal (anterior circulation territory), occipital, and cerebellar areas (posterior circulation territory). RESULTS: The thyroid on the whole-body scan was visualized after the Valsalva maneuver in 2 of the 10 patients. In 7 of 10 patients, 56 ROIs in the visualized cortical uptake showed that the distribution of MAA correlated well with that of HMPAO according to the equation: HMPAO = -71.21 + 1.71 x MAA, (r = 0.575, P < 0.01). The excess difference in the relative counts in the posterior over anterior circulation territory was 5.6% and 16.1% of the HMPAO and MAA values, respectively. CONCLUSION: Brain SPECT with (99m)Tc-MAA was more sensitive than thyroid visualization in detecting right-to-left shunt. The excess flow in the posterior cerebral circulation indicated an increased likelihood of cerebral emboli originating from the lower extremities and indicated that the flow difference between HMPAO and MAA probably resulted from poor linearization of HMPAO in the high-flow area.     

Verapamil does not inhibit 99mTcN-NOET uptake in situ in normal or ischemic canine myocardium.

Bis(N-ethoxy,N-ethyldithiocarbamato)nitrido technetium (V) ((99m)Tc) ((99m)TcN-NOET) is a new myocardial perfusion imaging agent currently undergoing phase III clinical trials in the United States and in Europe. (99m)TcN-NOET cellular uptake has been shown to be inhibited by the calcium channel inhibitor verapamil in cultured newborn rat cardiomyocytes. However, the effect of verapamil on in situ (99m)TcN-NOET myocardial uptake remains unknown. Therefore, the aim of this study was to evaluate whether the inhibitory effect of verapamil on the cellular uptake of (99m)TcN-NOET shown in vitro could be reproduced in situ in a canine model of normal and ischemic myocardium. METHODS: (99m)TcN-NOET uptake in normal and ischemic myocardium (70% flow reduction in the left anterior descending coronary artery) was measured in the absence or presence of verapamil (0.015 mg/kg/min x 10 min) in anesthetized, open-chest dogs (n = 17). Control animals were infused with adenosine (0.2 mg/kg/min) to match the verapamil-induced increase in flow. RESULTS: By verapamil treatment, a clinically relevant plasma concentration of the calcium channel inhibitor was attained (mean +/- SEM, 290 +/- 152 ng/mL). In normal myocardium (n = 8), regional blood flow at the time of (99m)TcN-NOET injection was not statistically different in verapamil- and adenosine-treated dogs (1.69 +/- 0.03 vs. 1.61 +/- 0.04 mL/min/g, respectively). (99m)TcN-NOET uptake was slightly higher in the presence of verapamil (0.39 +/- 0.01 vs. 0.38 +/- 0.01 counts per minute [cpm]/[Bq/kg]/g for adenosine; P = 0.04). However, no significant difference in (99m)TcN-NOET myocardial uptake was observed after normalization of the tracer uptake to regional myocardial blood flow. In ischemic myocardium (n = 9), regional blood flow was lower in verapamil-treated than in adenosine-treated animals (0.22 +/- 0.02 vs. 0.29 +/- 0.03 mL/min/g; P < 0.05). (99m)TcN-NOET uptake in the ischemic area was not inhibited by verapamil (0.09 +/- 0.01 vs. 0.10 +/- 0.01 cpm/[Bq/kg]/g; P = not significant). CONCLUSION: Verapamil does not inhibit (99m)TcN-NOET uptake in situ in normal and ischemic canine myocardium. These results suggest that verapamil should not affect (99m)TcN-NOET myocardial uptake in patients referred for myocardial perfusion imaging.     

Technetium-99m labeling of N-[N-(3-diphenylphosphino propionyl)glycyl]cysteine (PN2S-OH) and its methyl ester derivative (PN2S-OMe)

N-[N-(3-diphenylphosphinopropionyl)glycyl]cysteine and its methyl ester derivative were labeled with (99m)Tc at neutral pH, leading to a single species in high yield (>95%) in 30 min. RP-HPLC comparison with the analogue Re(V)-oxo complexes identified the labeled compounds as the anti isomers of pentacoordinated (99m)TcO[PN(2)S]-OH and (99m)TcO[PN(2)S]-OMe complexes. The compounds are stable from pH 7 to pH 9 when (99m)TcO[PN(2)S]-OH interconverts to related syn isomer, while (99m)TcO[PN(2)S]-OMe undergoes both saponification and interconversion. They exhibit high stability in human plasma and in vivo (mice), and a biodistribution characterized by hepatobiliary excretion.     

99mTc-exametazime as a breast tumor-seeking agent: comparison with 99mTc-sestamibi.

(99m)Tc-sestamibi is commonly used for mammoscintigraphy. Occasional uptake of (99m)Tc-exametazime in various tumors has been described. In this study, an intraindividual comparison of these 2 radiopharmaceuticals for mammoscintigraphy was made. METHODS: A kinetic study (30 min) in the lateral prone view of 20 breast tumors (> or =1 cm) in 20 women was conducted with (99m)Tc-exametazime. Thereafter, 21 breast tumors (> or =1 cm) in 21 women were examined with both agents (2 patients were included in both groups) under identical conditions (interval, 2-7 d). In the latter group, the tumor-to-background breast activity ratio and the tumor uptake normalized to the administered activity (cps/MBq) at 10 min after injection were calculated and compared for both agents. RESULTS: All tumors (43 tumors in 39 patients) were visualized with (99m)Tc-exametazime. There was also one instance of false-positive uptake using this agent. The uptake phase lasted approximately 10 min. Thereafter, the activity was practically stable. (99m)Tc-Sestamibi failed to depict 4 tumors. On the group level, the tracers did not differ in tumor-to-background activity ratio or normalized tumor uptake. Intraindividual agreement in tumor-to-background ratios between the tracers was moderate (intraclass correlation coefficient = 0.49). CONCLUSION: Uptake of (99m)Tc-exametazime in breast tumors > or = 1 cm seems to be comparable with that of (99m)Tc-sestamibi at a group level. The specificity is unknown. There is a restricted intraindividual agreement between the tracers, confirming different uptake mechanisms. This may open up possibilities for assessing different tumor characteristics in vivo, especially since the uptake of both agents is based on mechanisms believed to be involved in resistance to antineoplastic drugs.     

Arterial clearance and cerebral uptake of Tc-99m ECD in patients with cerebrovascular disease compared with PET]

Technetium-99m ethyl cysteinate dimer (ECD) has recently developed for SPECT imaging in assessment of cerebral perfusion. We evaluated the arterial blood clearance and the regional brain uptake of Tc-99m ECD compared with the regional CBF measured by PET in patients with cerebrovascular disease. Nine patients with diagnosis of cerebral ischemic disorders (N = 7) and cerebral hemorrhage (N = 2) were studied. PET study was performed with HEADTOME IV by O-15 steady state inhalation method. Immediately after the PET study, 555-740 MBq (5-20 mCi) of Tc-99m ECD was injected intravenously. After injection arterial blood sampling was performed sequentially, and we separated lipophilic fraction from whole blood using ethyl acetate in two cases. The SPECT imaging with Tc-99m ECD (ECD-SPECT) was started 5 min (first imaging) and 60 min (second imaging) after the administration using a high resolution ring type SPECT system (HEADTOME II). Several ROIs were placed on practically the same anatomical location on both SPECT and PET images. Clearance of the tracer in arterial whole blood and lipophilic fraction was rapid. Concerning to the distribution pattern of ECD-SPECT images there was no differences between the 1st imaging and the 2nd imaging, although about 15% of diffuse decrease of Tc-99m ECD uptake was shown in the 2nd images. The brain distribution of ECD-SPECT was comparable to the pattern of CBF image by PET. The regional relative counts of ECD-SPECT corresponded closely to the CBF value by PET, but it was no linear correlation between brain uptake of ECD-SPECT and PET-CBF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neonatal hypothyroid disease: absent salivary gland evident on technetium-99m pertechnetate scan

PURPOSE: Technetium-99m pertechnetate scintigraphy is a well-established technique for diagnosing congenital hypothyroid disease. However, the biodistribution of pertechnetate (TcO4-) in neonates and young infants is not well documented. The purpose of this study was to analyze and document the biodistribution of TcO4- in young infants. MATERIALS AND METHODS: Scintigraphic studies of 31 patients being examined for hypothyroid disease were analyzed. All patients had elevated levels of thyroid-stimulating hormone. Dyshormonogenesis was diagnosed in 7 patients, ectopic thyroid glands in 19, and agenesis in 5. RESULTS: Images of the neck, chest, and abdomen taken in the anterior and left lateral positions using a low-energy, all-purpose collimator were reviewed. Twenty-six of the patients had no accumulation of the isotope in the salivary glands and 11 had no gastric uptake on either view. CONCLUSIONS: Based on the absence of salivary gland activity in the patients examined, this study suggests that this is a normal finding in infants younger than 3 months. A lateral view of the neck with markers is sufficient to localize the thyroid gland, because any activity in the neck region would belong to the thyroid. Furthermore, poor and variable uptake of the isotope in the stomach may lead to false-negative results, so caution is urged in the use of this tracer in Meckel's scintigraphy in young infants, particularly if the study findings are within normal limits.     

Radioisotopic measurement of glomerular filtration rate in severe chronic renal failure

In order to determine the best method for routine measurement of glomerular filtration rate (GFR) in severe renal failure, we compared simultaneously the urinary clearances of [99mTc] diethylenetriaminepentaacetic acid (DTPA) (UD), [125I]iothalamate (UI), 24-hr creatinine clearance (UC) and plasma clearance of [99mTc]DTPA (PD), based on three plasma samples. In 60 studies in 22 patients with serum creatinine values of 2 to 8 mg/dl, UD and UI were almost identical: UD = 0.358 +/- 0.976 UI +/- 0.87 ml/min, r = 0.990. However, PD overestimated UD by a large and variable extent: PD = 11.3 +/- 0.843 UD +/- 5.5 ml/min, r = 0.694, and was inconsistent in sequential measurements in individual patients. UC also overestimated urinary isotope clearance: UC = 4.2 + 0.95 UI +/- 3.9 ml/min, r = 0.865. Sequential measurements of GFR in five patients with severe but stable renal failure (mean GFR 5.9 ml/min) showed an average standard deviation of only 0.83 ml/min. Thus both UD and UI appear to be reliable and precise measures of GFR in severe renal failure.     

Early uptake of 99mTc-C2A in the acute phase of myocardial infarction as a prognostic indicator for follow-up cardiac dysfunction

OBJECTIVE: The C2A domain of Synaptotagmin I is a molecular probe for the specific imaging of cell death. Here we test the hypothesis that the uptake of 99mTc-C2A in the acute phase of an infarction is associated with cardiac dysfunction in follow-ups. METHODS: The left coronary artery was occluded in Sprague-Dawley rats for 0, 10, 20, and 30 min. 99mTc-C2A was injected intravenously at 2 h of reperfusion. Anterior planar images were acquired with one million counts on a gamma camera 3 h after injection. 99mTc-C2A uptake was calculated as the total counts in the left ventricle region minus blood pool signal. The in-vivo signal detected was correlated with wall motion score index at 1 and 3 weeks follow-ups measured by echocardiography. RESULTS: 99mTc-C2A uptake was higher with increased ischemic time (2244+/-852, 4054+/-1223, and 6178+/-1451 for 10, 20, and 30 min ischemia, analysis of variance P<0.001). A significant correlation was found between 99mTc-C2A uptake and wall motion score index at 1 week (R=0.800, P=0.0006) and 3 weeks (R=0.810, P=0.0008). CONCLUSION: In this ischemia/reperfusion model, 99mTc-C2A uptake in the acute phase was associated with functional abnormality at 1 and 3 weeks. This demonstrates the potential diagnostic and prognostic value of 99mTc-C2A as a novel imaging agent.     

Respiratory clearance of aerosolized radioactive solutes of varying molecular weight

To determine the influence of varying molecular weight (mol wt) on respiratory clearance of aerosolized solutes, we studied eight radiopharmaceuticals, each administered to four dogs: sodium 99mTc pertechnetate (TcO4), 99mTc glucoheptonate ([99mTc]GH), 51Cr-ethylenedinitrotetraacetate ([51Cr]EDTA), 99mTc diethylenetriaminepentaacetate ([99mTc] DTPA), 111In diethylenetriaminepentaacetate ([111In]DTPA), 67Ga desferoxaminemesylate ([67Ga]DFOM), 99mTc dextran ([99mTc]DX) and 111In transferrin ([111In]TF). After aerosolization (0.8 m MMD, 2.4 GSD), clearance was determined for 30 min and then corrected by intravenous injection for nonairspace radioactivity. In-TF clearance (0.11 +/- 0.10%/min) was lower than TcO4 (6.32 +/- 0.62%/min), [99mTc]GH (1.50 +/- 0.37%/min), [51Cr]EDTA (2.38 +/- 1.02%/min), [99mTc]DTPA (3.51 +/- 0.40%/min), [111In]DTPA (2.35 +/- 0.42%/min), [67Ga] DFOM (1.99 +/- 0.49%/min) and [99mTc]DX (1.81 +/- 0.75%/min) clearances (p less than 0.001). TcO4 clearance was higher than others (p less than 0.001). Technetium binding to DX was unsatisfactory; aerosolization caused unbinding from DTPA. We conclude that respiratory clearance of large mol wt solutes within 30 min is negligible and, that clearance of molecules between 347-5,099 daltons differs greatly, suggesting that binding and/or intrapulmonary retention affect transfer.     

<Superscript>99m</Superscript>Tc sestamibi myocardial perfusion scintigraphy with the novel use of metamizol for the detection of perfusion reversibility

PURPOSE: This study aims to investigate whether induction with metamizol, an analgesic-antipyretic drug having spasmolitic activity, could be used to increase the detectability of ischemic/jeopardized myocardium during MPS (myocardial perfusion scintigraphy). MATERIALS AND METHODS: Metamizol-enhanced rest MPS (45 min after administration of 1 g metamizol orally, 740 MBq (99m)Tc sestamibi was injected, MPS was acquired 45 min later) was performed in 21 patients who had perfusion defects on their previous stress-rest (99m)Tc sestamibi MPS. Blood pressure was monitored at 15-min intervals. Stress, rest, metamizol-rest MPS images were interpreted on the model of 20 segments using a visual uptake score (VUS; 0 = normal, 1 = mild, 2 = moderate, 3 = significant decreases, 4 = no uptake). (99m)Tc sestamibi uptake ratios (MIBI-UR; mean counts in the region of the perfusion defect/mean counts in the region of the normal-perfused wall) were obtained on each MPS and compared with each other. Average MIBI-UR in each scintigraphic examination was calculated. MPS were compared with coronary angiography results. RESULTS: VUS and MIBI-UR results showed that metamizol-rest MPS displayed the defect reversibility better than rest MPS. Of the 14 segments with fixed perfusion defects on stress-rest MPS, 8 showed improvement of perfusion after metamizol induction. In 33 segments, lesion reversibility was better delineated on metamizol-rest MPS. Metamizol-induced sestamibi uptake was significantly higher (p < 0.001) than stress/baseline rest examinations as calculated by the MIBI-UR. Blood pressure remained unaltered. Coronary angiography results were in concordance with metamizol induced MPS. CONCLUSIONS: Metamizol-enhanced rest MPS increases detectability of ischemic/viable myocardium during MPS. Metamizol should be discontinued like nitrates before stress MPS since it may mask the visualization of ischemic perfusion defects.     

Technetium-99m tetrofosmin imaging in thyroid diseases: comparison with Tc-99m-pertechnetate,thallium-201 and Tc-99m-methoxyisobutylisonitrile scans

Technetium-99m tetrofosmin is a lipophilic phosphine used for myocardial perfusion imaging. Biodistribution studies have shown significant thyroid uptake of tetrofosmin and preliminary reports have suggested that tetrofosmin imaging may be of value in patients with thyroid cancer. In this study, tetrofosmin whole-body scintigraphy was performed in 35 patients with evidence of thyroid diseases. All patients underwent laboratory evaluation of thyroid function as well as^99mTc pertechnetate scan, thallium-201 (n=16)^99mTc-methoxyisobutylisonitrile (MIBI) (n=19) whole-body studies. Thyroid images were semi-quantitatively analysed by a 4-point score: O=no significant uptake; 1=uptake increased as compared to background activity, but inferior to normal thyroid tissue; 2=uptake equal to normal thyroid tissue; 3=uptake superior to normal thyroid tissue. Pathology examinations were obtained. A total of 41 thyroid nodules were detected, of which 15 were goitre nodules, 13 adenomas and 13 malignant lesions. In goitre nodules, concordant results of tetrofosmin and pertechnetate uptake (score 1 or 0) were observed in the majority of lesions (87%). In function adenomas (n=10), both tetrofosmin uptake and pertechnetate uptake were score 3. In non-function adenomas (n=3), tetrofosmin uptake was score 3, while pertechnetate uptake was score 0. In six malignant lesions, tetrofosmin uptake was score 3, while pertechnetate uptake was score 0; in the other seven lesions, where a prevalence of goitre abnormalities was observed, results of tetrofosmin and pertechnetate uptake were similar (score 0 or 1). In seven (70%) of the ten patients with malignant nodules, whole-body tetrofosmin images showed increased abnormal uptake in a total of 28 extra-thyroid tumour sites, as subsequently confirmed by other techniques. When tetrofosmin images were compared to 201T1 and^99mTc-MIBI scans, concordant results were observed in all cases. In conclusion, tetrofosmin imaging may be particularly useful to characterize and stage patients with malignant thyroid nodules; it shows similar results to thallium but provides better image quality. Comparable findings were observed between tetrofosmin and MIBI studies. Thus, tetrofosmin may be an alternative to thallium and MIBI in the aforementioned patients.