Validation of a new cycle ergometer

The purpose of this study was to test the concurrent validity of the ICBE compared to the Monark(?) cycle ergometer by indirect dynamic calibration. 42 men were randomly submitted to 2 maximal stress tests with increments of 50 W at 2-min intervals. One test was performed on the Monark(?) bicycle (834/E) and the other on the ICBE. Cardiovascular, perceived exertion and hemodynamic responses were compared between the 2 bicycles. No differences (p>0.05) were observed in resting heart rate (HR), maximum HR, peak oxygen uptake (VO(2P) L·min(-1) and VO(2P) mL·kg(-1)·min(-1)), and number of stages completed. High correlations (r>0.85) were found between HR and VO (2P). Residual analysis indicated strong agreement between the 2 cycle ergometers in terms of VO(2P) L·min(-1) [-0.36-0.30] and VO(2P) mL·kg(-1)·min(-1) [-4.98-4.46]. Residual dispersion (r=0.25 for both) showed that the mathematical differences in VO(2P) L·min(-1) and VO(2P) mL·kg(-1)·min(-1) between cycle ergometers were independent. The correlation coefficient (r) and coefficient of determination (R(2)) between VO(2P) L·min(-1) (r=0.90; R (2)=0.80) and VO(2P) mL·kg(-1)·min(-1) (r=0.90; R(2)=0.81) obtained for the 2 cycle ergometers were high, whereas the standard error of the estimate was low (0.186 L·min(-1) and 2.56 mL·kg(-1)·min(-1), respectively). The ICBE presents concurrent validity for use in submaximal and maximal cardiopulmonary tests.     

Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography.

The purpose of this study was to evaluate the feasibility of absolute quantification of regional cerebral glucose utilization (rCMR(glc)) in mice by use of (18)F-FDG and a small animal PET scanner. rCMR(glc) determined with (18)F-FDG PET was compared with values determined simultaneously by the autoradiographic 2-(14)C-DG method. In addition, we compared the rCMR(glc) values under isoflurane, ketamine and xylazine anesthesia, and awake states. METHODS: Immediately after injection of (18)F-FDG and 2-(14)C-DG into mice, timed arterial samples were drawn over 45 min to determine the time courses of (18)F-FDG and 2-(14)C-DG. Animals were euthanized at 45 min and their brain was imaged with the PET scanner. The brains were then processed for 2-(14)C-DG autoradiography. Regions of interest were manually placed over cortical regions on corresponding coronal (18)F-FDG PET and 2-(14)C-DG autoradiographic images. rCMR(glc) values were calculated for both tracers by the autoradiographic 2-(14)C-DG method with modifications for the different rate and lumped constants for the 2 tracers. RESULTS: Average rCMR(glc) values in cerebral cortex with (18)F-FDG PET under normoglycemic conditions (isoflurane and awake) were generally lower (by 8.3%) but strongly correlated with those of 2-(14)C-DG (r(2) = 0.95). On the other hand, under hyperglycemic conditions (ketamine/xylazine) average cortical rCMR(glc) values with (18)F-FDG PET were higher (by 17.3%) than those with 2-(14)C-DG. Values for rCMR(glc) and uptake (percentage injected dose per gram [%ID/g]) with (18)F-FDG PET were significantly lower under both isoflurane and ketamine/xylazine anesthesia than in the awake mice. However, the reductions of rCMR(glc) were markedly greater under isoflurane (by 57%) than under ketamine and xylazine (by 19%), whereas more marked reductions of %ID/g were observed with ketamine/xylazine (by 54%) than with isoflurane (by 37%). These reverse differences between isoflurane and ketamine/xylazine may be due to competitive effect of (18)F-FDG and glucose uptake to the brain under hyperglycemia. CONCLUSION: We were able to obtain accurate absolute quantification of rCMR(glc) with mouse (18)F-FDG PET imaging as confirmed by concurrent use of the autoradiographic 2-(14)C-DG method. Underestimation of rCMR(glc) by (18)F-FDG in normoglycemic conditions may be due to partial-volume effects. Computation of rCMR(glc) from (18)F-FDG data in hyperglycemic animals may require, however, alternative rate and lumped constants for (18)F-FDG.     

Reducing renal uptake of 90Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

OBJECTIVE: The purpose of this study was to improve the tumor-to-kidney uptake ratios of (90)Y- and (177)Lu-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys(3,4,10), d-Phe(7), Arg(11)]alpha-melanocyte stimulating hormone(3-13) {DOTA-Re(Arg(11))CCMSH} through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. METHODS: A new peptide of DOTA-Re(Glu(2), Arg(11))CCMSH was designed, synthesized and labeled with (90)Y and (177)Lu. Pharmacokinetics of (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH was determined in B16/F1 murine melanoma-bearing C57 mice. RESULTS: (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH exhibited significantly (P<.05) less renal uptake values than (90)Y- and (177)Lu-DOTA-Re(Arg(11))CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The renal uptake values of (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH were 28.16% and 28.81% of those of (90)Y- and (177)Lu-DOTA-Re(Arg(11))CCMSH, respectively, at 4 h postinjection. (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH displayed higher tumor-to-kidney uptake ratios than (90)Y- and (177)Lu-DOTA-Re(Arg(11))CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The tumor-to-kidney uptake ratio of (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH was 2.28 and 1.69 times of (90)Y- and (177)Lu-DOTA-Re(Arg(11))CCMSH, respectively, at 4 h postinjection. The (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH activity accumulation was low in normal organs except for kidney. CONCLUSIONS: Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of (90)Y- and (177)Lu-DOTA-Re(Glu(2), Arg(11))CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma.     

The addition of DTPA to [<Superscript>177</Superscript>Lu-DOTA<Superscript>0</Superscript>,Tyr<Superscript>3</Superscript>]octreotate prior to administration reduces rat skeleton uptake of radioactivity

Peptide receptor-targeted radionuclide therapy is nowadays also being performed with DOTA-conjugated peptides, such as [DOTA(0),Tyr(3)]octreotate, labelled with radionuclides like (177)Lu. The incorporation of (177)Lu is typically >/=99.5%; however, since a total patient dose can be as high as 800 mCi, the amount of free (177)Lu(3+) (= non-DOTA-incorporated) can be substantial. Free (177)Lu(3+) accumulates in bone with unwanted irradiation of bone marrow as a consequence. (177)Lu-DTPA is reported to be stable in serum in vitro, and in vivo it has rapid renal excretion. Transforming free Lu(3+) to Lu-DTPA might reroute this fraction from accumulation in bone to renal clearance. We therefore investigated: (a) the biodistribution in rats of (177)LuCl(3), [(177)Lu-DOTA(0),Tyr(3)]octreotate and (177)Lu-DTPA; (b) the possibilities of complexing the free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate to (177)Lu-DTPA prior to intravenous injection; and (c) the effects of free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate, in the presence and absence of DTPA, on the biodistribution in rats. (177)LuCl(3) had high skeletal uptake (i.e. 5% ID per gram femur, with localization mainly in the epiphyseal plates) and a 24-h total body retention of 80% injected dose (ID). [(177)Lu-DOTA(0),Tyr(3)]octreotate had high and specific uptake in somatostatin receptor-positive tissues, and 24-h total body retention of 19% ID. (177)Lu-DTPA had rapid renal clearance, and 24-h total body retention of 4% ID. Free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate could be complexed to (177)Lu-DTPA. Accumulation of (177)Lu in femur, blood, liver and spleen showed a dose relation to the amount of free (177)Lu(3+), while these accumulations could be normalized by the addition of DTPA. After labelling [DOTA(0),Tyr(3)]octreotate with (177)Lu the addition of DTPA prior to intravenous administration of [(177)Lu-DOTA(0),Tyr(3)]octreotate is strongly recommended.     

An artificial amino acid, 4-iodo-L-meta-tyrosine: biodistribution and excretion via kidney.

We evaluated the use of radiolabeled 4-iodo-L-meta-tyrosine as an amino acid transport marker. The pharmacologic features of this compound, particularly the biodistribution and excretion, were examined by conducting in vivo and in vitro studies using 4-(125)I-iodo-L-meta-tyrosine (4-(125)I-mTyr). Results obtained for L-(14)C-Tyr and 3-(125)I-iodo-alpha-methyl-L-tyrosine ((125)I-IMT) were used for comparison. METHODS: In vivo biodistribution studies of 4-(125)I-mTyr were performed in male ddY mice. Urinary excretion of 4-(125)I-mTyr and (125)I-IMT with administration of probenecid was studied. Local distribution of 4-(125)I-mTyr and (125)I-IMT in kidney was visualized by autoradiography. We performed metabolite analysis of 4-(125)I-mTyr in mice. For in vitro studies, reabsorption mechanisms of 4-(125)I-mTyr were compared with those of (125)I-IMT and the parent L-(14)C-Tyr using superconfluent monolayers of the porcine kidney epithelial cell line LLC-PK(1) in medium containing inhibitor (L-Tyr, D-Tyr, and 2,4-dinitrophenol), in Na(+)-free medium, and at 4 degrees C. RESULTS: 4-(125)I-mTyr demonstrated high accumulation in the pancreas and kidney and comparable brain uptake to that of (125)I-IMT. Blood clearance of 4-(125)I-mTyr was faster than that of (125)I-IMT. Three hours after administration, >70% of 4-(125)I-mTyr was excreted via the urine, whereas <5% was found in the feces. Renal autoradiography revealed moderate accumulation of 4-(125)I-mTyr and high accumulation of (125)I-IMT in the renal cortex. Probenecid further reduced accumulation of 4-(125)I-mTyr and (125)I-IMT in the kidney as well as urinary excretion. At 30 min after tracer injection, intact free 4-(125)I-mTyr accounted for >98.1% of the total present in kidney and >96.3% in urine. Protein incorporation was not observed. Uptake of 4-(125)I-mTyr into LLC-PK(1) cell monolayers was remarkably reduced by 5 mmol/L L-Tyr (4.6%) and incubation at 4 degrees C (15.6%) but was reduced by 5 mmol/L D-Tyr (50.0%). L-(14)C-Tyr and (125)I-IMT showed similar results; however, uptake of (125)I-IMT was enhanced by 0.1 mmol/L 2,4-dinitrophenol (165.1%), an inhibitor of generation of energy-rich phosphates. CONCLUSION: The artificial amino acid 4-(125)I-mTyr demonstrated high metabolic stability, rapid blood clearance, rapid urinary excretion, and similar biodistribution to other radiolabeled L-Tyr analogs. 4-(125)I-mTyr can be a competitive substrate of L-Tyr reabsorption. However, 4-(125)I-mTyr demonstrates different pharmacologic features than those of (125)I-IMT, particularly in renal handling. 4-(125)I-mTyr may potentially be applied as a new amino acid transport marker.     

123I-5-IA-85380 SPECT measurement of nicotinic acetylcholine receptors in human brain by the constant infusion paradigm: feasibility and reproducibility.

(123)I-5-IA-85380 ((123)I-5-IA; [(123)I]-5-iodo-3-[2(S)-azetidinylmethoxy]pyridine) is a promising SPECT radiotracer for imaging beta(2)-containing nicotinic acetylcholine receptors (beta(2)-nAChRs) in brain. Beta(2)-nAChRs are the initial site of action of nicotine and are implicated in various neuropsychiatric disorders. The feasibility and reproducibility of the bolus-plus-constant-infusion paradigm for equilibrium modeling of (123)I-5-IA using SPECT in healthy nonsmokers was studied. METHODS: Ten healthy nonsmokers (mean age +/- SD, 43.7 +/- 9.9 y) underwent two (123)I-5-IA SPECT scans within 4 wk. (123)I-5-IA was administered as a bolus (125.8 +/- 14.6 MBq) plus constant infusion (18.1 +/- 1.5 MBq/h). SPECT acquisitions (30 min) and venous blood sampling were performed every 60 min throughout the infusion (10-14 h). The test-retest variability and reliability of plasma activity (kBq/mL), the regional brain activity reflected by units of kBq/mL and %ID/mL (injected dose/mL brain tissue), and the equilibrium outcome measures V(T)' (ratio of total uptake to total plasma parent concentration) and V(T) (ratio of total uptake to free plasma parent concentration) were evaluated in 4 brain areas, including thalamus, striatum, cortex, and cerebellum. RESULTS: Linear regression analysis revealed that time-activity curves for both plasma and brain (123)I-5-IA activity stabilized by 5 h, with an average change of [2.5%/h between 6 and 8 h of infusion, permitting equilibrium modeling. The plasma free fraction (f(1)), total parent, and clearance demonstrated good test-retest variability (mean, 10.9%-12.5%), whereas the variability of free parent was greater (mean, 24.3%). Regional brain activity (kBq/mL) demonstrated good test-retest variability (11.1%-16.4%) that improved when corrected for infusion rate (mean, 8.2%-9.9%) or for injected dose (mean, 9.5%-13.3%). V(T)' demonstrated better test-retest variability (mean, 7.0%-8.9%) than V(T) (mean, 12.9%-14.6%). Reliability assessed by the intraclass correlation coefficient (ICC) was superior for kBq/mL (ICC = 0.83-0.90) and %ID/mL (ICC = 0.93-0.96) compared with V(T)' (ICC = 0.30-0.64) and V(T) (ICC = 0.28-0.60). The lower reliability of V(T) was attributed to the poor reliability of the free fraction (ICC = 0.35) and free parent (ICC = 0.68). CONCLUSION: These results support the feasibility and reproducibility of equilibrium imaging with (123)I-5-IA for measurement of beta(2)-nAChRs in human brain.     

Peak power output, the lactate threshold, and time trial performance in cyclists.

PURPOSE: To determine the relationship between maximum workload (W(peak)), the workload at the onset of blood lactate accumulation (W(OBLA)), the lactate threshold (W(LTlog)) and the D(max) lactate threshold, and the average power output obtained during a 90-min (W(90-min)) and a 20-min (W(20-min)) time trial (TT) in a group of well-trained cyclists. METHODS: Nine male cyclists (.VO(2max) 62.7 +/- 0.8 mL.kg(-1).min(-1)) who were competing regularly in triathlon or cycle TT were recruited for the study. Each cyclist performed four tests on an SRM isokinetic cycle ergometer over a 2-wk period. The tests comprised 1) a continuous incremental ramp test for determination of maximal oxygen uptake (.VO(2max) (L.min(-1) and mL.kg(-1).min(-1)); 2) a continuous incremental lactate test to measure W(peak), W(OBLA), W(LTlog), and the D(max) lactate threshold; and 3) a 20-min TT and 4) a 90-min TT, both to determine the average power output (in watts). RESULTS: The average power output during the 90-min TT (W(90-min)) was significantly (P < 0.01) correlated with W(peak) (r = 0.91), W(LTlog) (r = 0.91), and the D(max) lactate threshold (r = 0.77, P < 0.05). In contrast, W(20-min) was significantly (P < 0.05) related to .VO(2max) (L.min(-1)) (r = 0.69) and W(LTlog) (r = 0.67). The D(max) lactate threshold was not significantly correlated to W(20-min) (r = 0.45). Furthermore, W(OBLA) was not correlated to W(90-min) (r = 0.54) or W(20-min) (r = 0.23). In addition, .VO(2max) (mL.kg(-1).min(-1)) was not significantly related to W(90-min) (r = 0.11) or W(20-min) (r = 0.47). CONCLUSION: The results of this study demonstrate that in subelite cyclists the relationship between maximum power output and the power output at the lactate threshold, obtained during an incremental exercise test, may change depending on the length of the TT that is completed.     

Comparison of integrin alphaVbeta3 expression and glucose metabolism in primary and metastatic lesions in cancer patients: a PET study using 18F-galacto-RGD and 18F-FDG.

The expression of alpha(v)beta(3) and glucose metabolism are upregulated in many malignant lesions, and both are known to correlate with an aggressive phenotype. We evaluated whether assessment of alpha(v)beta(3) expression and of glucose metabolism with PET using (18)F-galacto-RGD and (18)F-FDG provides complementary information in cancer patients. METHODS: Eighteen patients with primary or metastatic cancer (non-small cell lung cancer [NSCLC], n = 10; renal cell carcinoma, n = 2; rectal cancer, n = 2; others, n = 4) were examined with PET using (18)F-galacto-RGD and (18)F-FDG. Standardized uptake values (SUVs) were derived by volume-of-interest analysis. (18)F-Galacto-RGD and (18)F-FDG PET results were compared using linear regression analysis for all lesions (n = 59; NSCLC, n = 39) and for primaries (n = 14) and metastases to bone (n = 11), liver (n = 10), and other organs (n = 24) separately. RESULTS: The sensitivity of (18)F-galacto-RGD PET compared with clinical staging was 76%. SUVs for (18)F-FDG ranged from 1.3 to 23.2 (mean +/- SD, 7.6 +/- 4.9) and were significantly higher than SUVs for (18)F-galacto-RGD (range, 0.3-6.8; mean +/- SD, 2.7 +/- 1.5; P < 0.001). There was no significant correlation between the SUVs for (18)F-FDG and (18)F-galacto-RGD for all lesions (r = 0.157; P = 0.235) or for primaries, osseous or soft-tissue metastases separately (P > 0.05). For the subgroup of lesions in NSCLC, there was a weak correlation between (18)F-FDG and (18)F-galacto-RGD uptake (r = 0.353; P = 0.028). CONCLUSION: Tracer uptake of (18)F-galacto-RGD and (18)F-FDG does not correlate closely in malignant lesions. Whereas (18)F-FDG PET is more sensitive for tumor staging, (18)F-galacto-RGD PET warrants further evaluation for planning and response evaluation of targeted molecular therapies with antiangiogenic or alpha(v)beta(3)-targeted drugs.     

Effect of ramp slope on ventilation thresholds and VO2peak in male cyclists.

This study investigated the effect of 10 W*min(-1) (Slow ramp, SR), 30 W*min(-1) (Medium ramp, MR) and 50 W*min(-1) (Fast ramp, FR) exercise protocols on assessments of the first (VT1) and second (VT2) ventilation thresholds and peak oxygen uptake (VO(2)peak) in 12 highly-trained male cyclists (mean +/- SD age = 26 +/- 6 yr). Expired gas sampled from a mixing chamber was analyzed on-line and VT1 and VT2 were defined as two break-points in 20-s-average plots of pulmonary ventilation (V(E)), ventilatory equivalents for O(2) (V(E)/VO(2)) and CO(2) (V(E)/VCO(2)), and fractions of expired O(2) (F(E)O(2)) and CO(2) (F(E)CO(2)). Arterialized-venous blood samples were analyzed for blood-gas and acid-base status. VO(2)peak was significantly lower (p < 0.05) for SR (4.65 +/- 0.53 l small middle dot min(-1)) compared to MR (4.89 +/- 0.56 l *min(-1)) and FR (4.88 +/- 0.57 l *min(-1)) protocols. CO(2) output and blood PCO(2) were lower (p < 0.05), and V(E)/VCO(2) was higher (p < 0.05), above VT1 for SR compared to MR and FR protocols. No significant differences were observed among the protocols for VO(2), % VO(2)peak, V(E), plasma lactate ([La(-)]) and blood hydrogen ion concentration ([H(+)]), and heart rate (HR) values at VT1 or VT2. The work rate (WR) measured at VT1, VT2 and VO(2)peak increased (p < 0.05) with steeper ramp slopes. It was concluded that, in highly-trained cyclists, assessments of VT1 and VT2 are independent of ramp rate (10, 30, 50 W*min(-1)) when expressed as VO(2), % VO(2)peak, V(E), plasma [La(-)], blood [H(+)] and HR values, whereas VO(2)peak is lower during 10 W*min(-1) compared to 30 and 50 W*min(-1) ramp protocols. In addition, the WR measured at VT1, VT2 and VO(2)peak varies with the ramp slope and should be utilized cautiously when prescribing training or evaluating performance.     

Effect of warm-up on cycle time trial performance

PURPOSE: This study was designed to determine the effect of warm-up on 3-km cycling time trial (TT) performance, and the influence of accelerated VO(2) kinetics on such effect. METHODS: Eight well-trained road cyclists, habituated to 3-km time trials, performed randomly ordered 3-km TT after a) no warm-up (NWU), b) easy warm-up (EWU) (15 min comprised of 5-min segments at 70, 80, and 90% of ventilatory threshold (VT) followed by 2 min of rest), or c) hard warm-up (HWU) (15 min comprised of 5-min segments at 70, 80, and 90% VT, plus 3 min at the respiratory compensation threshold (RCT) followed by 6 min of rest). VO(2) and power output (SRM), aerobic and anaerobic energy contributions, and VO(2) kinetics (mean response time to 63% of the VO(2) observed at 2 km) were determined throughout each TT. RESULTS: Three-kilometer TT performance was (P < 0.05) improved for both EWU (266.8 +/- 12.0 s) (-2.8%) and HWU (267.3 +/- 10.4 s) (-2.6%) versus NWU (274.4 +/- 12.1 s). The gain in performance was predominantly during the first 1000 m in both EWU (48% of gain) and HWU (53% of gain). This reflected a higher power output during the first 1000 m in both EWU (384 W) and HWU warm-up (386 W) versus NWU (344 W) trials. The mean response time was faster in both EWU (45 +/- 10 s) and HWU (41 +/- 12 s) versus NWU (52 +/- 13 s) trials. There were no differences in anaerobic power output during the trials, but aerobic power output during the first 1000 m was larger during both EWU (203 W) and HWU (208 W) versus NWU (163 W) trials. CONCLUSIONS: During endurance events of intermediate duration (4-5 min), performance is enhanced by warm-up irrespective of warm-up intensity. The improved performance is related to an acceleration of VO(2) kinetics.     

Production and separation of Astatine Radionuclides: some new addition to Astatine Chemistry.

For the first time no-carrier-added (nca) (209,210)At radionuclides were produced by heavy ion ((7)Li) activation from 4 mg/cm(2) lead nitrate target. Astatine was separated from the bulk target by three different approaches. Nca astatine radionuclide was selectively partitioned in the (i) polymer rich phase of an aqueous biphasic system consisting of polyethylene glycol (PEG) 4000 (50% w/w) and 2M Na(2)SO(4) solution (ii) aqueous phase of a liquid liquid extraction system being comprised of a liquid cation exchanger, HDEHP (di-2-ethylhexyl phosphoric acid) (0.5%) and liquor ammonia (iii) liquid phase of a solid liquid extraction system of cation exchange resin Dowex-50 and 10(-6)M HCl. Very high separation factors have been achieved in all the three methods.     

Potential of (99m)Tc-MIBI for detecting bone marrow metastases.

In this study, we evaluated the potential of (99m)Tc-hexakis-2-methoxyisobutylisonitrile (MIBI) for detecting bone metastases in comparison with a conventional bone tracer. METHODS: (99m)Tc-MIBI and (99m)Tc-hydroxymethylene diphosphonate (HMDP) scans were obtained from 99 patients with proven malignant diseases and suspected bone metastases. We compared 373 lesions that showed abnormal uptake on (99m)Tc-MIBI scans or (99m)Tc-HMDP scans (or both). RESULTS: Bone metastases were confirmed in 334 of 373 lesions. Thirty-nine lesions on (99m)Tc-HMDP scans had false-positive findings, but only 2 of these lesions had false-positive findings on (99m)Tc-MIBI scans. (99m)Tc-MIBI and (99m)Tc-HMDP scans were equivalent in 168 of 334 lesions (50.3%). (99m)Tc-MIBI scans correctly detected more lesions than (99m)Tc-HMDP scans: 284 lesions (85.0%) versus 218 lesions (65.3%) (P < 0.005), respectively. (99m)Tc-MIBI scans showed a markedly higher sensitivity for detecting metastases in the femur and humerus compared with (99m)Tc-HMDP scans: 97 of 98 lesions (99.0%) versus 35 of 98 lesions (35.7%) (P < 0.005) and 21 of 22 lesions (95.5%) versus 11 of 22 lesions (50.0%) (P < 0.005), respectively. (99m)Tc-HMDP scans of 17 patients showed no abnormal images. However, (99m)Tc-MIBI scans correctly detected bone metastases, and subsequent development of multiple lesions was observed on follow-up (99m)Tc-HMDP scans of 15 patients. (99m)Tc-MIBI scans were superior to (99m)Tc-HMDP scans in the detection of metastases attributed to breast cancer, multiple myeloma, and hepatoma. On the contrary, (99m)Tc-MIBI scans were less sensitive than (99m)Tc-HMDP scans for detecting bone metastases attributed to prostate cancer in the other skeletal sites except for femur and humerus. CONCLUSION: (99m)Tc-MIBI scans have better sensitivity for detecting bone metastases and provide more specific complementary findings than conventional bone scans. (99m)Tc-MIBI accumulation attributed to bone marrow metastases may occur at an early stage, before the bone remodeling process in the surrounding bone can be detected on conventional bone scans.     

Quantitative 89Zr immuno-PET for in vivo scouting of 90Y-labeled monoclonal antibodies in xenograft-bearing nude mice.

Immuno-PET as a scouting procedure before radioimmunotherapy (RIT) aims at the confirmation of tumor targeting and the accurate estimation of radiation dose delivery to both tumor and normal tissues. Immuno-PET with (89)Zr-labeled monoclonal antibodies (mAbs) and (90)Y-mAb RIT might form such a valuable combination. In this study, the biodistribution of (89)Zr-labeled and (88)Y-labeled mAb ((88)Y as substitute for (90)Y) was compared and the quantitative imaging performance of (89)Zr immuno-PET was evaluated. METHODS: Chimeric mAb (cmAb) U36, directed against an antigen preferentially expressed in head and neck cancer, was labeled with (89)Zr using the bifunctional chelate N-succinyldesferrioxamine B (N-sucDf) and with (88)Y using the bifunctional chelate p-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bz-DOTA). The radioimmunoconjugates were coinjected in xenograft-bearing nude mice, and biodistribution was determined at 3, 24, 48, 72, and 144 h after injection. (89)Zr was evaluated and compared with (18)F in phantom studies to determine linearity, resolution, and recovery coefficients, using a high-resolution research tomograph PET scanner. The potential of PET to quantify cmAb U36-N-sucDf-(89)Zr was evaluated by relating image-derived tumor uptake data (noninvasive method) to (89)Zr uptake data derived from excised tumors (invasive method). RESULTS: (89)Zr-N-sucDf-labeled and (88)Y-p-SCN-Bz-DOTA-labeled cmAb U36 showed a highly similar biodistribution, except for sternum and thigh bone at later time points (72 and 144 h after injection). Small differences were found in kidney and liver. Imaging performance of (89)Zr approximates that of (18)F, whereas millimeter-sized (19-154 mg) tumors were visualized in xenograft-bearing mice after injection of cmAb U36-N-sucDf-(89)Zr. After correction for partial-volume effects, an excellent correlation was found between image-derived (89)Zr tumor radioactivity and gamma-counter (89)Zr values of excised tumors (R(2) = 0.79). CONCLUSION: The similar biodistribution and the favorable imaging characteristics make (89)Zr a promising candidate for use as a positron-emitting surrogate for (90)Y.     

Synthesis and in vivo evaluation of 2 high-affinity 76Br-labeled sigma2-receptor ligands.

The sigma(2)-receptor has been shown to be upregulated in proliferating tumors cells. The purpose of this study was to compare 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) and 2 new (76)Br-radiolabeled compounds that have a high affinity and selectivity for the sigma(2)-receptor. These are 5-bromo-N-(4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butyl)-2,3-dimethoxybenzamide (compound (1)) and 5-bromo-N-(2-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)ethyl)-2-methoxybenzamide (compound (2)). METHODS: Two sigma(2)-receptor-binding ligands were prepared, from the corresponding tributylstannyl precursors using standard electrophilic chemistry, (76)Br-compound (1) ((76)Br-1) and (76)Br-compound (2) ((76)Br-2). (18)F-FLT, (76)Br-1, and (76)Br-2 were compared using allograft tumors of the EMT-6 cell line (mouse mammary adenocarcinoma) in biodistribution studies at 5 min, 0.5, 1, and 2 h. Imaging of (76)Br-1 and (18)F-FLT was also performed at 2 and 1 h, respectively. RESULTS: (76)Br-1 and (76)Br-2 were synthesized with yields between 50% and 70% with high specific activity. Both compounds showed uptake into the tumor with tumor-to-normal tissue ratios of (76)Br-1 being greater than both (76)Br-2 and (18)F-FLT. Except for the liver and kidney, all ratios were greater than 1 and uptake into the tumor was shown with microPET imaging for (76)Br-1. CONCLUSION: We were able to synthesize two (76)Br-radiolabeled compounds with a high yield and specific activity that target the sigma(2) receptor with high affinity and selectivity. The studies presented show that both of the flexible benzamide compounds can identify EMT-6 breast tumors in vivo. (76)Br-1 also has higher tumor-to-normal tissue ratios when compared with (76)Br-2 and (18)F-FLT. The high affinity and low nonspecific binding of (76)Br-1 indicates that it can be a potential PET radiotracer for imaging solid tumors.     

Production of high purity (94m)Tc for positron emission tomography studies

The radioisotope (94m)Tc (T(1/2) = 52.5 min; I(beta)+ = 72%; E(beta)+ = 2.47 MeV) is of considerable interest for quantitative biodistribution studies of Tc radiopharmaceuticals using positron emission tomography. The nuclear processes (94)Mo(p,n), (93)Nb((3)He, 2n), (92)Mo(alpha,pn), and (92)Mo(alpha,2n)(94)Ru --> (94m)Tc are of potential interest for the production of (94m)Tc. Detailed cross section and yield measurements showed that the (94)Mo(p,n)-reaction over the energy range E(p) = 13 --> 7 MeV is most suitable: The yield of (94m)Tc is high (2 GBq/muAh), the impurity level is low (provided highly-enriched (94)Mo is used as target material), and a small-sized cyclotron is adequate. Using conventional targetry, sufficient quantities of the radioisotope can be produced. The chemical processing methods employed include both solvent extraction and thermochromatography. The quality of the final product is discussed.     

Side effects of anabolic androgenic steroids abuse

Long-term side effects of high doses of anabolic androgenic steroids self-administration were evaluated in this study. Twenty male bodybuilders, voluntarily starting steroid self-administration, were followed every 6 months over 2 years. Physical examination, haematological, metabolic and endocrine variables, semen analysis, hepatic and prostate ultrasound and echocardiographic evaluations were performed. LH values (baseline 3.43 +/- 1.75) were suppressed at 18 (1.98 +/- 1.99) (p = 0.026) and 24 (2.43 +/- 2.17) (p = 0.026), and FSH (3.95 +/- 2.01) at 6 (3.01 +/- 2.16) (p = 0.031), 12 (2.45 +/- 2.54) (p = 0.029), 18 (2.02 +/- 2.29) (p = 0.032) and 24 (3.42 +/- 2.64) (p = 0.032) months and SHBG (34.11 +/- 10.88) values significantly lowered at 12 (24.81 +/- 12.49) (p < 0.05), 18 (21.28 +/- 11.15) (p < 0.01), 24 months (25.42 +/- 11.16) (p < 0.01). A significant decrease in spermatozoa count (p < 0.01), and fertility index (p = 0.01) occurred. HDL-cholesterol (baseline 56.94 +/- 13.54) was reduced at 18 (41.86 +/- 14.17) (p < 0.01) and 24 (43.82 +/- 18.67) (p < 0.05) months and Apo A-1 at 12 (p < 0.001), 18 (p = 0.05) and 24 (p = 0.05) months. The most important long-term adverse effects were lower fertility and the impairment of lipid profile associated with an increased cardiovascular risk.     

Synthesis of new carbon-11 labeled naphthalene-sulfonamides for PET imaging of human CCR8.

Carbon-11 labeled naphthalene-sulfonamides, N-(4-(N-(4-[(11)C]methoxyphenyl)sulfamoyl)naphthalene-1-yl)benzamide ([(11)C]5a), N-(4-(N-(4-[(11)C]methoxyphenyl)sulfamoyl)naphthalene-1-yl)-2-methylbenzamide ([(11)C]5b), N-(4-(N-(4-[(11)C]methoxyphenyl)sulfamoyl)naphthalene-1-yl)-3-methylbenzamide ([(11)C]5c), N-[(11)C]methyl-N-methyl-4-(4-benzamidonaphthalene-1-sulfonamido)piperidine-1-carboxamide ([(11)C]9a) and N-[(11)C]methyl-N-methyl-4-(4-(2-methylbenzamido)naphthalene-1-sulfonamido)piperidine-1-carboxamide ([(11)C]9b), have been synthesized as new potential positron emission tomography (PET) agents for imaging of human CCR8. The target tracers were prepared by either O-[(11)C]methylation or N-[(11)C]methylation of their corresponding precursors using [(11)C]CH(3)OTf and isolated by either a simplified solid-phase extraction (SPE) purification procedure or a high pressure liquid chromatography (HPLC) method in 30-50% radiochemical yields decay corrected to end of bombardment (EOB), 20-25min overall synthesis time, and 74-111GBq/mumol specific activity at end of synthesis (EOS).     

Comparison of polarization transfer sequences for enhancement of signals in clinical 31P MRS studies.

Several (31)P MRS studies in tumors in vivo have shown that levels of phosphocholine (PC) and other phosphomonoesters (PME) and phosphodiesters (PDE) are useful prognostic or early-response indicators. To improve sensitivity for such measurements, four polarization transfer (PT) sequences (insensitive nuclei enhanced by PT (INEPT), distortionless enhancement by PT (DEPT), reverse-INEPT, and heteronuclear single-quantum coherence (HSQC)) were assessed theoretically and experimentally. The presence of homonuclear ((1)H-(1)H) and heteronuclear ((31)P-(1)H) couplings of similar magnitude makes theoretical analysis very sensitive to precise model parameters, especially for the (1)H-detected sequences. The (1)H-(1)H coupling causes the splitting of (1)H peaks, and hence reduces the proton spectral resolution. This effect and a 50% signal loss from gradient-enhanced water suppression negate the usual advantages of (1)H-detection. Among the PT methods, INEPT gave the higher signal enhancement. However, T(2) losses during the long echo times (TEs) required by the weak coupling limited the resulting signals from PC.     

Diffusion-weighted MRI in the evaluation of renal lesions: preliminary results

The purpose of this study was to evaluate the capability and the reliability of diffusion-weighted MRI in the evaluation of normal kidney and different renal lesions. 39 patients (10 normal volunteers and 29 patients with known renal lesions) underwent MRI of the kidneys by using a 1.5 T superconducting magnet. Axial fat suppressed turbo spin echo (TSE) T(2) and coronal fast field echo (FFE) T(1) or TSE T(1) weighted images were acquired for each patient. Diffusion-weighted (DW) images were obtained in the axial plane during breath-hold (17 s) with a spin-echo echo planar imaging (SE EPI) single shot sequence (repetition time (TR)=2883 ms, echo time (TE)=61 ms, flip angle=90 degrees ), with b value of 500 s mm(-2). 16 slices were produced with slice thickness of 7 mm and interslice gap of 1 mm. An apparent diffusion coefficient (ADC) map was obtained at each slice position. The ADC was measured in an approximately 1 cm region of interest (ROI) within the normal renal parenchyma, the detected renal lesions and the collecting system if dilated. ADC values in normal renal parenchyma ranged from 1.72 x 10(-3) mm(2) s(-1) to 2.65 x 10(-3) mm(2) s(-1), while ADC values in simple cysts (n=13) were higher (2.87 x 10(-3) mm(2) s(-1) to 4.00 x 10(-3) mm(2) s(-1)). In hydronephrotic kidneys (n=6) the ADC values of renal pelvis ranged from 3.39 x 10(-3) mm(2) s(-1) to 4.00 x 10(-3) mm(2) s(-1). In cases of pyonephrosis (n=3) ADC values of the renal pelvis were found to be lower than those of renal pelvis of hydronephrotic kidneys (0.77 x 10(-3) mm(2) s(-1) to 1.07 x 10(-3) mm(2) s(-1)). Solid benign and malignant renal tumours (n=7) showed ADC values ranging between 1.28 x 10(-3) mm(2) s(-1) and 1.83 x 10(-3) mm(2) s(-1). In conclusion diffusion-weighted MR imaging of the kidney seems to be a reliable way to differentiate normal renal parenchyma and different renal diseases. Clinical experience with this method is still preliminary and further studies are required.