The impact of one HF-rTMS session on mood and salivary cortisol in treatment resistant unipolar melancholic depressed patients.

BACKGROUND: Recent studies indicate that medication resistant depressed patients can be successfully treated by a series of sessions of High Frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS), delivered on the left dorsolateral prefrontal cortex (DLPFC). However, changes in subjectively experienced mood give only limited insight into the underlying physiological responses. Previous studies in depressed patients, as well as in healthy volunteers, have reported a possible impact of HF-rTMS on the hypothalamic-pituitary-adrenal (HPA) axis. OBJECTIVE: We wanted to evaluate the emotional and neurobiological impact of one session of HF-rTMS applied on the left DLPFC in a sample of unipolar treatment resistant depressed patients of the melancholic subtype. METHODS: 20 right-handed antidepressant-free depressed patients were studied using a sham-controlled, 'single' blind, crossover design. We examined subjective mood changes with Visual Analogue Scales (VAS). To examine HF-rTMS effects on the HPA-axis, we analyzed salivary cortisol levels. Mood assessment and salivary cortisol levels were assessed before and immediately after stimulation. To detect any delayed effects, all measurements were also re-assessed 30 min post HF-rTMS. The left DLPFC was determined under MRI guidance. RESULTS: One session of HF-rTMS did not result in any subjectively experienced mood changes. However, salivary cortisol concentrations decreased significantly immediately and 30 min after active HF-rTMS. CONCLUSIONS: Although one session of HF-rTMS on the left DLPFC did not influence mood subjectively in melancholic unipolar depressed patients, we found support for the hypothesis that a single session has a significant impact on the HPA-axis, as measured by salivary cortisol. Our results may provide more insight into the underlying working mechanisms of HF-rTMS in unipolar melancholic depression, and could add further information about endocrinological functioning in affective disorders.

The early effect of proton pump inhibitor therapy on the accuracy of the 13C-urea breath test.

BACKGROUND: The intake of proton pump inhibitors may interfere with the reliability of the urea breath test. AIM: Prospective study to assess the accuracy of the urea breath test during the first days of therapy with proton pump inhibitors. PATIENTS: Thirty patients who needed to start proton pump inhibitors therapy and 53 volunteers. METHODS: A 13C-urea breath test was performed respectively before starting proton pump inhibitors therapy and every morning before its intake up until 10 days. The test was considered positive for values of 13CO2 > or = 3.0% delta over baseline. The coefficient of reproducibility for 95% interval of confidence of the urea breath test was calculated in both groups. RESULTS: Of the 30 patients receiving proton pump inhibitors, 47% were positive for Helicobacter pylori. Among these, 43% developed false negative breath tests in the first 10 days. False positive results occurred in 37.5% of H. pylori-negative subjects in the first 10 days. The coefficient of reproducibility of the urea breath test was significantly higher in the group treated with proton pump inhibitors (11.0 versus 1.8 for the control group, p < 0.0001). CONCLUSION: The intake of proton pump inhibitors impairs the accuracy of the 13C-urea breath test. False negative and false positive 13C-urea breath tests are common, occur as soon as after 1 day and increase with prolonged duration of treatment. The coefficient of reproducibility of the test in patients receiving proton pump inhibitors is not acceptable for clinical purpose and the test should not be performed once the medication has been started.

Drainage pattern of the upper medial quadrant of the breast in young healthy women after subdermal injection: a lymphscintigraphic study.

This study examines the lymphatic drainage after injection of a radiotracer in the upper medial quadrant of the right breast in young healthy female subjects. Most studies concerning lymphatic drainage pathways have focused on the upper lateral quadrant of the breast because of the high incidence of carcinoma in this quadrant while the drainage pattern of the medial quadrant has been less studied. We injected radiotracer (Human Serum Albumin labeled with 99 technetium) subdermally into the upper medial quadrant of the right breast tissue of 33 young healthy female volunteers and obtained static images with a scintillation camera briefly after injection and approximately one hour after injection. We identified lymphatic pathways in 82.8% of our subjects, lymph nodes in 79.3% and in 3.4%, a sentinel lymph node was found in the internal mammary chain. In early images, lymph nodes were visualized in 65.5% of subjects while in 17.2% of subjects, lymphatic vessels only appeared on later images.

Dopamine D2 receptors in depression measured with single photon emission computed tomography.

Psychobiological theories of mood disorders have been concerned mainly with noradrenaline and serotonin. There exists, however, a recent upsurge of interest in dopamine. We have used single photon emission computed tomography and 123I-iodobenzamide, a high-affinity ligand for D2 receptors, to study these receptors in depression. Subjects were 21 (unipolar) depressed inpatients and 11 normal controls. The mean basal ganglia/cerebellum uptake ratio was 1.94 (+/- 0.27) in the depressed patients versus 1.74 (+/- 0.17) in the controls. This difference was statistically significant (Mann-Whitney U test, p = 0.025). These data could indicate an increase of D2 receptor density in depression.

Prospective evaluation of technetium-99m-HMPAO SPECT in mild and moderate traumatic brain injury.

UNLABELLED: We prospectively evaluated the contribution of 99mTc-HMPAO SPECT in patients who have sustained acute, mild or moderate head trauma. METHODS: Forty-two patients formed the first subgroup of moderate trauma (ModTr) and 25 patients formed the second subgroup of mild trauma (MilTr). All 67 patients underwent an initial SPECT (Tinit) within 4 wk after a closed cranial trauma. After a mean interval of 3 mo from the time of Tinit, all patients were clinically re-evaluated; those with an abnormal Tinit underwent a repeat SPECT (Trpt) as well. All SPECT studies were visually graded by agreement of three observers adjudging a score ranging from 0 (no lesions) to 4. RESULTS: For the group as a whole (ModTr + MilTr), the following results could be derived: (1) in 32/33 Tinit negative cases, clinical symptoms had resolved; (2) the positive predictive value of Tinit was only 20/34 (59%); (3) the sensitivity for the repeat SPECT was 19/20 (95%). CONCLUSION: Our results show that: (1) SPECT alterations correlate well with the severity of the trauma; (2) a negative initial SPECT study is a reliable predictor of a favorable clinical outcome; (3) in cases with a positive initial SPECT, a follow-up consisting of a combination of SPECT and clinical data is necessary; (4) in patients suffering from postconclusive symptoms, SPECT offers an instrument to objective sequelae.

Technetium-99m-tetrofosmin in dipyridamole-stress myocardial SPECT imaging: intraindividual comparison with technetium-99m-sestamibi.

UNLABELLED: Tetrofosmin is a new 99mTc-labeled myocardial perfusion imaging agent. Biodistribution studies suggest more favorable heart-to-adjacent organ biokinetics than for 99mTc-sestamibi after injection during exercise. The aim of this work was to determine intraindividually whether tetrofosmin is more suitable than sestamibi for pharmacological stress testing in a 1-day protocol. METHODS: Thirty subjects underwent two similar 1-day, rest and dipyridamole stress imaging protocols: one using tetrofosmin, the other using sestamibi. SPECT was performed 60 min after tracer administration. Myocardial images were analyzed both visually and quantitatively. RESULTS: Heart-to-liver activity ratios measured on the anterior SPECT projections were significantly higher for tetrofosmin than for sestamibi in the rest and stress studies. Heart-to-lung ratios were similar for both tracers. Significant linear correlations between tetrofosmin and sestamibi perfusion indices were found in normals and in patients with proven or suspected coronary artery disease. In segments showing abnormal uptake during stress, the perfusion indices were similar for tetrofosmin and sestamibi at rest and during stress. The degree of reversibility in these segments was also similar for both tracers. Finally, the extent, intensity and severity of perfusion defects were similar for both tracer studies. CONCLUSION: Tetrofosmin has a more optimal biodistribution than sestamibi when used in a 1-day, rest and dipyridamole stress myocardial SPECT imaging protocol. No significant difference in either the quality or diagnostic interpretation of the images could be demonstrated.

Visualizing ocular melanoma using iodine-123-N-(2-diethylaminoethyl)4-iodobenzamide SPECT.

UNLABELLED: Radiolabeled benzamides have recently been introduced for the detection of melanoma. We evaluated the potential clinical applicability of 123I-N-(2-diethylaminoethyl) 4-iodobenzamide ([123I]IDAB) for SPECT imaging of ocular melanoma. METHODS: Fourteen patients were studied, 10 with or suspected of malignant ocular melanoma and four with ocular naevi. All patients underwent SPECT imaging of the head and whole-body scintigraphy 4-5 hr after injection of 170 MBq [123I]IDAB. RESULTS: A definite tracer hyperfixation was observed in the pathological eye in 9 of 10 (90%) patients with ocular melanoma. The pathological-to-normal eye ratio averaged 1.46 (range 1.07-2.86). The melanoma nature of the scintigraphic lesions was confirmed after enucleation in eight cases and by clinical evolution in two. A false-negative scan was reported in a patient with a small and hypochromic lesion. In patients with ocular naevi, no false-positive scintigrams were documented. CONCLUSION: Iodine-123-IDAB scintigraphy may contribute significantly to decide about enucleation in cases where some doubt persists with conventional techniques.

One-year follow-up of technetium-99m-HMPAO SPECT in mild head injury.

UNLABELLED: We evaluated the predictive capacity of 99mTc-HMPAO SPECT for clinical outcome during a follow-up period of 12 mo after mild head injury. METHODS: We prospectively evaluated 136 patients with mild head injury who underwent initial SPECT imaging (SPECTO) within 4 wk after the trauma. Re-evaluations were made 2.9-3.3 mo (T3mo), 5.7-6.3 mo (T6mo) and 11.9-12.6 mo (T12mo) postinjury. All patients with an abnormal SPECT underwent a repeat study at the subsequent time of evaluation. Patients with a previously normal SPECT scan did not undergo a repeat study. Clinical reassessments (CLIN) were performed as long as the earlier study had been positive or until patients were completely asymptomatic. RESULTS: During all follow-up evaluations, SPECT had a high sensitivity and negative predictive value, increasing from 91% and 89%, respectively, at T3mo to 100% at T6mo and at T12mo. Clinical normalization occurred earlier than scintigraphic normalization. However, at 12 mo postinjury, we observed considerable improvement in the specificity and positive predictive value of SPECT (85% and 83%, respectively). The persistent lesions on the SPECT scan were related to their severity and to localization in the frontal cortex. CONCLUSION: A normal 99mTc-HMPAO SPECT scan is a reliable tool in the exclusion of clinical sequelae of mild head injury. At 12 mo postinjury, a positive SPECT study is also a reliable predictor for clinical outcome.

Renal technetium-99m-DMSA SPECT in normal volunteers.

UNLABELLED: Dimercaptosuccinic acid (DMSA) renal scintigraphy today is considered a sensitive and useful technique for the detection of cortical abnormalities. Recent studies have suggested that lesion detection can be improved by SPECT imaging. This study investigated normal kidneys using different SPECT modalities. METHODS: Ten young, healthy volunteers with normal clinical history and normal renal ultrasound underwent planar and SPECT DMSA imaging 2 to 4 hr after intravenous injection of 99mTc-DMSA (185 MBq). Analysis of SPECT data was focused on the homogeneity of cortical uptake (comparison of upper and lower pole activity) as well as on the presence or absence of focal cortical defects. RESULTS: No abnormality could be observed on the planar images. SPECT revealed, in seven kidneys (five left and two right), the presence of a hypoactive upper pole. This was visually observed on the coronal slices with up to 35% difference between upper and lower pole. Moreover, three focal cortical defects were visualized on the coronal slices as well as on three-dimensional surface shade displays. CONCLUSION: These normal patterns should be recognized when evaluating a patient with possible renal involvement.

Effect of oral glucose loading on the biodistribution of BMIPP in normal volunteers.

UNLABELLED: We have evaluated whether myocardial uptake of the fatty acid analog 123I-15-(p-iodophenyl)-3-R,S-methyl pentadecanoic acid (BMIPP) is dependent on the dietary state. METHODS: We compared the biodistribution of 150 MBq of 123I-BMIPP in six healthy volunteers in two states: after at least 12 hr of fasting and after oral glucose loading (75 g) 60 min before tracer administration, followed by a meal enriched in carbohydrates and protein. Planar and tomographic acquisitions were performed over a 4-hr time period after tracer injection; data were corrected for radioactive decay and injected dose. Radioactivity was measured in blood samples drawn at several points. RESULTS: Significant increases of glycemia and insulinemia and a significant drop in plasma nonesterified acids were documented after glucose loading. Half-time values for plasma radioactivity were significantly shorter in the glucose-loaded state than in the fasted state (4.3 +/- 1.4 min compared to 6.3 +/- 1.3 min, p < 0.05). Activity in the heart and liver tended to be higher in the glucose-loaded state than in the fasted state. SPECT images at 0.5 hr after tracer injection demonstrated that the myocardial wall-to-cavity ratio was higher after glucose than in the fasted state (2.53 +/- 0.59 compared to 2.11 +/- 0.21, p = 0.15). Washout from the liver between 1 and 4 hr after injection increased from 18.6% +/- 4.4% in the fasted study to 24.1% +/- 2.4% after glucose (p = 0.04). Washout from the myocardium between 0.5 and 3.5 hr after injection increased from 13.1% +/- 8.8% in the fasted study to 24.0% +/- 3.7% after glucose (p = 0.05). CONCLUSION: These results indicate that fasting before BMIPP scintigraphy is not mandatory to obtain adequate SPECT images. At the tire when SPECT is usually performed, glucose loading may provide improved ratios between myocardial and blood pool activity.

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.

Evaluation of 99mTc-RP128 as a potential inflammation imaging agent: human dosimetry and first clinical results.

UNLABELLED: 99mTc-RP128 is a bifunctional peptide chelate designed to target the tuftsin receptor, expressed by neutrophils, monocytes, and macrophages. Studies in animal models of both infectious and noninfectious inflammation have shown a positive correlation between accumulation of 99mTc-RP128 and quantitative measures of inflammation. A phase 1 trial was conducted with the objective of determining the safety, biodistribution, and human dosimetry of 99mTc-RP128 in eight healthy volunteers. For evaluation of the potential of 99mTc-RP128 for imaging sites of inflammation, 10 patients with active rheumatoid arthritis were studied. METHODS: Normal biodistribution was determined using the conjugate view method up to 24 h after intravenous injection of 280 MBq 99mTc-RP128. Dosimetry calculations were based on standard MIRD methodology, using the International Commission on Radiological Protection model 30 of the gastrointestinal tract and a voiding bladder model with an interval of 4.8 h. For rheumatoid arthritis patients, whole-body scans and spot views of the hands, knees, and feet were obtained at 1 and 3 h after injection of 475 MBq 99mTc-RP128. RESULTS: 99mTc-RP128 was cleared rapidly from the blood by renal excretion, and no major organs showed significant accumulation. The synovia of the major joints were visualized for all subjects. The effective dose equivalent and the effective dose were calculated to be 0.011 and 0.0094 mSv/MBq, respectively. The highest dose was to the bladder wall, which received 0.076 mGy/MBq. In all rheumatoid arthritis patients, we observed a markedly increased uptake in several affected joints. Painful and swollen joints were detected with a sensitivity of 76% and 69%, respectively. Seventy-three percent of the joints with radiographic signs of erosion were scintigraphically positive. In some patients, lines of increased activity were observed and were considered to correspond to uptake in the synovium lining tendon sheaths in the wrists and hands. CONCLUSION: This study shows that 99mTc-RP128 is safe and can successfully be used to visualize clinically affected joints in patients with long-standing rheumatoid arthritis. A proposed radioactive dose of 450-500 MBq will produce an effective dose well within the range of effective doses for commonly used radiopharmaceuticals.

Automatic determination of left ventricular ejection fraction from gated blood-pool tomography.

UNLABELLED: The aim of this study was to develop and validate a new algorithm to automatically compute left ventricular ejection fraction (LVEF) from gated blood-pool tomography (GBPT). The results were compared with those of conventional planar radionuclide angiocardiography (PRNA). METHODS: Fifty-three consecutive patients received an injection of 740 MBq (99m)Tc-labeled human serum albumin. PRNA and GBPT were performed consecutively in a random sequence. PRNA served as the reference, and GBPT images were processed using a new edge detection algorithm. The algorithm is fast (<45 s), fully automatic, and works in three-dimensional space. The method includes identification of the valve plane and the septum. The left ventricular cavity at end-diastole is delineated by segmentation using an iterative threshold technique. An optimal threshold is reached when the corresponding isocontour best fits the first derivative of the end-diastolic count distribution in three dimensions. This optimal threshold is then applied to delineate the left ventricular cavity on the other time bins. The data are corrected for the partial-volume effect. Left ventricular volumes are determined using a geometry-based method and are used to calculate the ejection fraction. RESULTS: The success rate of the new algorithm was 94%. LVEFs calculated from GBPT agreed well with those calculated from PRNA (r = 0.78; GBPT = 0.94 PRNA + 6.33). The systematic error was 2.8%, and the random error was 8.8%. Excellent inter- and intraobserver reproducibility was found, with average differences of 1.1% +/- 4.6% and 1.1% +/- 5.0%, respectively, between the two measurements. CONCLUSION: This new algorithm provides a fast, automated, and objective method to calculate LVEF from GBPT.

Abnormal free fatty acid uptake in subacute myocardial infarction after coronary thrombolysis: correlation with wall motion and inotropic reserve.

UNLABELLED: Iodine-123-free fatty acid analogs, such as beta-methyliodophenylpentadecanoic acid (BMIPP), allow for myocardial metabolic studies with SPECT. The goal of this investigation was to determine whether BMIPP uptake can be used to differentiate viable myocardium from scar tissue soon after coronary thrombolysis for acute myocardial infarction. METHODS: BMIPP and 99mTc-sestamibi (MIBI) myocardial distribution after injection at rest were analyzed in 22 patients 4 to 10 days after coronary thrombolysis. The relative uptake of the two tracers was compared on a segmental basis to the regional wall motion and to the inotropic reserve assessed by two-dimensional echocardiography and low-dose dobutamine stimulation. RESULTS: Three segmental patterns were identified in the infarct-related coronary artery territory. Segments with normal BMIPP and MIBI uptake showed normal wall motion. Segments with more reduced BMIPP uptake than MIBI uptake (mismatching) showed either normal wall motion or demonstrated inotropic reserve during dobutamine stimulation. Segments with matched defects always showed abnormal wall motion and did not demonstrate inotropic reserve, regardless of the MIBI uptake. CONCLUSION: In patients with subacute myocardial infarction, combined imaging of BMIPP and MIBI at rest might be more sensitive than MIBI or wall motion at rest alone to demonstrate myocardial areas that have been acutely ischemic. Mismatching is due to more severely depressed fatty acid metabolism than expected on the basis of the flow and is indicative of jeopardized, but viable myocardium. In dysfunctional segments, mismatching may correspond either to stunned or to hibernating myocardium. Matched defects are associated with scar tissue.

Prediction of functional outcome after myocardial infarction using BMIPP and sestamibi scintigraphy.

UNLABELLED: We determined the predictive value of combined beta-methyl iodophenyl pentadecanoic acid (BMIPP) and sestamibi scintigraphy for the functional outcome after myocardial infarction and compared the value of this approach with dobutamine echocardiography. METHODS: Rest BMIPP, rest sestamibi and low-dose dobutamine echocardiographic studies were obtained in 18 patients 4 to 10 days after infarction (mean 6.7 +/- 2.0 days). Six months later, a rest echocardiographic study was performed to assess functional outcome. RESULTS: Wall motion improved in 27/33 segments (82%) which showed mismatching but not in 19/21 segments (90%) with matched defects (p < 0.001). The accuracy of combined BMIPP and sestamibi SPECT in predicting segmental functional outcome was higher (85%) than that of sestamibi uptake alone (77%). Wall motion improved in 16/20 segments (80%) showing contractile reserve and not in 21/34 segments (63%) with the negative dobutamine test, giving an accuracy of 69% for dobutamine echocardiography. Combination of the two techniques resulted in higher positive (94%) and negative predictive values (94%). CONCLUSION: Mismatching of BMIPP and sestamibi uptake is predictive for long-term functional recovery after acute myocardial infarction. In contrast, segments with matched defects contain only scar tissue. Combined BMIPP and sestamibi scintigraphy offers increased accuracy compared to dobutamine echocardiography.

Effect of PEEP on regional ventilation and perfusion in the mechanically ventilated preterm lamb.

Improvement of gas exchange through closer matching of regional ventilation (V) and lung perfusion (Q) with the application of positive end-expiratory pressure (PEEP) was evaluated in vivo in six mechanically ventilated preterm lambs (107-126 days/145 days gestation). Changes in V and Q were determined from in vivo scintigraphic measurements in four lung regions with inhaled radioactive 81mKr, and infused 81mKr/dextrose and/or [99mTc]MAA as PEEP was applied at 2, 4, and 6 cm H2O in each animal. Dynamic compliance varied between 0.02 and 0.40 ml/cm H2O, which was consistent with surfactant deficiency. As PEEP was increased, the regional distribution of Q shifted from the rostral to the caudal lung regions (p less than 0.02 to less than 0.05), while that of V remained unchanged. Regional V/Q matching improved together with a trend towards improvement of arterial blood gases as PEEP was increased from 2 to 4 cm H2O. Pulmonary scintigraphy offers a noninvasive methodology for the quantitative assessment of regional V and Q matching in preterm lambs and may be clinically applicable to ventilated neonates.

Technetium-99m-MRP20, a potential brain perfusion agent: in vivo biodistribution and SPECT studies in normal male volunteers.

The lipophilic neutral complex [99mTc][TcO(MRP20)] [MRP20 is (N-(2(1H pyrolylmethyl]N'-(4-pentene-3-one-2)ethane-1,2-diamine)] is known to cross the blood-brain barrier in non-primate animals. We report here its in vivo biodistribution, radiation dosimetry, and single-photon emission computed tomography (SPECT) characteristics in man. Following i.v. administration of 15-25 mCi of the tracer, the maximum uptake of activity in the brain peaked at 1 min p.i. Fifteen minutes p.i., the percentage retained in the brain was 5.2 +/- 1.6, which remained fairly constant over 24 hr. Blood clearance was relatively slow with an apparent affinity of the compound for the cellular fraction of the blood, however, soft-tissue and facial activity cleared at a rate four times faster than that of the brain. SPECT images obtained at 15 min, 1 hr, 3 hr, 7 hr, and 24 hr p.i. showed no redistribution of the tracer within the brain. The dosimetry is favorable for administration of 25-30 mCi of MRP20. Our results indicate that this compound is rapidly extracted and retained by the brain and may be used for SPECT imaging of regional blood flow.

Synthesis, radiosynthesis, and in vitro characterization of [125I]-2- iodo-L-phenylalanine in a R1M rhabdomyosarcoma cell model as a new potential tumor tracer for SPECT.

[125I]-2-iodo-L-phenylalanine, a new radioiodinated phenylalanine analog was evaluated as a potential specific tumor tracer for SPECT. The tracer is obtained with an overall radiochemical yield of at least 98%, a purity of > 99%, and a specific activity of 11 MBq/mmol in one pot Kit conditions using the Cu1+ assisted isotopic exchange. The tracer is evaluated in vitro using R1M rat rabdomyosarcoma cells in HEPES buffer with and without Na+ ions and in MEM buffer. The uptake of [125I]-2-iodo-L-phenylalanine follows a reversible pseudo-first-order reaction which is the same in presence and absence of Na+ ions, but the compound is not incorporated into the cell proteins. The reversible uptake is proven to occur with the same affinity as L-henylalanine by a saturable transport system which is competitively inhibited by BCH, an L transport type selective molecule. Trans-stimulation of the efflux by BCH and typical L transported amino acids shows that the transporter is of the antiport type and fulfils all the properties of the LAT1 heterodimer transport system. [125I]-2-iodo-L-phenylalanine is thus a phenylalanine analog that for the uptake uses for the major part the LAT1 transport system which is known to be over-expressed in tumor cells. This, together with the easy Kit preparation, makes [123I]-2-iodo-L-phenylalanine a promising tumor specific tracer for SPECT.

In vitro characterization of the influx of 3-[125I]iodo-L-alpha-methyltyrosine and 2-[125I]iodo-L-tyrosine into U266 human myeloma cells: evidence for system T transport.

The aim of this study was to investigate the cellular uptake mechanisms responsible for the accumulation of 3-[(125)I]iodo-L-alpha-methyltyrosine ((125)I-3-IMT) and 2-[(125)I]iodo-L-tyrosine ((125)I-2-IT), two radiotracers for metabolic tumor imaging, using single-photon emission tomography, into U266 human myeloma cancer cells. Time course and concentration dependency of (125)I-3-IMT uptake was assessed. Kinetic parameters were calculated using an Eadie Hofstee plot. A set of competitive inhibitors of the main amino acid transport systems was used for the discrimination of the transporters responsible for the uptake of (125)I-3-IMT and (125)I-2-IT. Protein incorporation of both tracers was determined using acid precipitation. The measured maximum velocity for (125)I-3-IMT transport was 4.199 nmol per mg protein 20 s(-1), and the Michaelis constant was 107.9 microM. Addition of 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH), a competitive inhibitor of System L, reduced the influx by 39.0+/-3.3% for (125)I-3-IMT and 66.3+/-0.9% for (125)I-2-IT. The BCH-insensitive influx was further reduced by Tryptophan (Trp) by 43.8+/-3.5% for (125)I-3-IMT and 15.3+/-1.3% for (125)I-2-IT. This suggests involvement of System T transport. We measured <2% of radioactivity in the acid precipitable fractions of both tracers with no increase in time. We conclude that the influx of (125)I-3-IMT and (125)I-2-IT into U266 human myeloma cells is mediated by both System L and System T amino acid transporters. The kinetic parameters suggest that elevated plasma levels of aromatic amino acids will reduce (123)I-3-IMT uptake in myeloma patients. Both tracers do not enter protein synthesis significantly.

Acute effects of oxygen, nifedipine, and diltiazem in patients with cystic fibrosis and mild pulmonary hypertension.

The acute effects of oxygen, nifedipine, and diltiazem were studied in eight patients with cystic fibrosis and mild pulmonary hypertension, to assess the possibility of relieving the latter before the occurrence of irreversible vascular changes. Oxygen decreased pulmonary pressure (-23%) and resistance (-21%), while increasing systemic resistance (+23%). Nifedipine increased cardiac index (+30%), at the expense of augmented right ventricular work (+42%), resulting in a decreased calculated pulmonary resistance (-23%); pulmonary artery pressure remained unchanged, however. Nifedipine decreased arterial Po2 (-10%), suggesting ventilation-perfusion mismatch. Four of the eight patients responded to diltiazem. Their pulmonary pressure (-35%) and resistance (-43%) decreased, while systemic vascular tone remained unchanged. Oxygen in three patients, and diltiazem in two, returned pulmonary pressures and resistances to normal values. Early reversal of pulmonary hypertension is possible, and intervention is desirable before the establishment of chronic hypoxia, cor pulmonale, or right ventricular failure. Our data does not support the use of nifedipine in pulmonary hypertension, but shows that oxygen, and in some cases diltiazem, act as effective and selective pulmonary vasodilators.