[Show abstract][Hide abstract] ABSTRACT: 99mTc-labeling studies have been performed on CCK(4) fragment of cholecystokinin, starting from 99mTc-pertechnetate, by using tin(II)pyrophosphate or tin(II)gluconate as reducing agents, together with NaBH(4) acting as a stabilizing agent of tin(II). Gluconate has been used as exchange ligand in the carrier added experiments and in the syntheses of 99Tc-CCK(4) and Re-CCK(4) complexes to be able to reproduce at macroscopic level the same chemical reactions occurring at non carrier added conditions. 99mTc-labeling yields higher than 95% have been achieved depending on Sn(II) concentration, CCK(4)/gluconate ratio, reaction time and applied temperature. The species produced with 99mTc, 99Tc, and cold rhenium nuclides have been compared by means of HPLC measurements, which showed similar retention times and thus probably the same species in the three situations.
Nuclear Medicine and Biology 11/2001; 28(7):865-73. · 2.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To improve standardization in analytical reagents we investigated Chloramine-T radioiodination (125I) of several biomolecules based on the use of a single amount of the oxidizing agent Chloramine-T as the limiting reagent being exhausted during the course of the reaction. Whenever the labeling yield resulted in less than one atom 125I/molecule, a second amount of the oxidizing agent was added. Thereafter, the integrity of the various biomolecules was assessed using radioimmunoassays, radioreceptor binding assays, or radioimmunometric assays. Purification yields were done by gel permeation (56% +/- 19%, n=230) or by precipitation with trichloroacetic acid (59% +/- 19%, n=230). Specific activity (117 +/- 61 MBq/nmol) and the degree of iodine incorporation (1.4 +/- 0.8 atoms of 125I/molecule) were achieved after 300 sec of incubation. A second addition of Chloramine-T resulted in an increased labeling yield of all biomolecules tested by a mean factor of 1.8 +/- 0.9. After the second addition of Chloramine-T, we observed for some biomolecules a significant (p<0.001) decreased effect in biological performance. In conclusion, the use of Chloramine-T as a limiting reagent resulted in molecules with appropriate immunological and biological performance. In general, tracers were minimally damaged and assessment of the shelf life as well as storing conditions showed the usefulness of the standardization of biomolecule labeling.
Nuclear Medicine and Biology 11/2001; 28(8):999-1008. · 2.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Positron emission tomography (PET) has evolved into a technique that can accurately determine the distribution of positron-emitting radionuclides. The addition of a coincidence detection mode to a standard dual-head detector system has resulted in the option of single-photon and annihilation coincidence detection. This new device for imaging fluorine-18 2-fluoro-2-deoxy-D-glucose (18F-FDG) accumulation in neoplasms became commercially available in 1994. Besides conventional low-energy imaging in the collimated single-photon mode, it offers a relatively inexpensive opportunity to perform uncollimated PET by switching to the coincidence acquisition mode. This review summarises the clinical value of 18F-FDG detection with a dual-head coincidence camera in oncology. The results are compared with the overall results obtained using dedicated PET scanners. With respect to head and neck tumours, 18F-FDG coincidence mode gamma camera imaging (CGI) yields results that are in agreement with those obtained with dedicated PET scanners. With regard to other malignancies, such as lung cancer, lymphoma and brain tumours, data in the literature are too scarce to draw any definite conclusions. In general, the results of 18F-FDG CGI in tumours >15 mm seem to be comparable to those obtained with dedicated PET scanners, whereas in tumours <15 mm, the relative sensitivity of 18F-FDG CGI is approximately 80%. Using attenuation correction, the diagnostic yield of 18F-FDG CGI may increase. However, further clinical investigation is required to definitely establish its value in staging primary disease, therapy monitoring and assessment of tumour recurrence in clinical oncology.
European Journal of Nuclear Medicine 07/2001; 28(6):763-78.
[Show abstract][Hide abstract] ABSTRACT: Gated single photon emission computed tomography (SPECT) imaging allows the simultaneous assessment of both perfusion and function by using one single study. The assessment of regional wall motion and thickening pattern with gated SPECT allows viability studies to be performed. Magnetic resonance imaging (MRI) is well validated for the assessment of myocardial wall motion and thickening in patients with normal and impaired ventricular function. The aim of the study was to analyse the concordance between wall motion and thickening scores derived by gated SPECT and MRI imaging. Furthermore, the agreement for myocardial wall motion and thickening according to myocardial perfusion was analysed with both techniques. We studied a group of 21 patients, including 13 with a previous myocardial infarction (all more than 4 months before the study), using both gated SPECT 99Tcm-tetrofosmin myocardial perfusion imaging and MRI. A 13-segment model was used for both gated SPECT and MRI and each segment was visually scored using a scale of 1-3 for wall motion and thickening. There was a high agreement between gated SPECT and MRI for both wall motion (229/273, 84%; k = 0.72, P<0.001) and wall thickening (236/273, 86%; k = 0.77, P<0.001). The agreement for wall motion and thickening was 80% (k = 0.66) and 83% (k = 0.70), respectively, for patients with myocardial infarction; and 90% (k = 0.81) and 92% (k = 0.86), respectively (P = NS), for patients without myocardial infarction. Agreement in segmental wall motion and thickening scores between gated SPECT and MRI was 90% (k = 0.80) and 91% (k = 0.84), respectively, for segments with normal or mild to moderate hypoperfusion; and 71% (k = 0.45) and 77% (k = 0.57), respectively, for segments with severe hypoperfusion or no perfusion. Of the 70 (41%) segments that had severely diminished or no perfusion in post-myocardial infarction patients, 22 (31%) showed preserved wall motion and 17 (24%) showed preserved wall thickening both by gated SPECT and MRI, suggesting residual myocardial viability in malperfused segments. Our results suggest that gated SPECT imaging is a reliable tool for the assessment of regional wall motion and thickening in patients with known or suspected coronary artery disease. In patients with a previous myocardial infarction gated SPECT imaging has the potential to detect preserved wall motion and thickening in regions with fixed perfusion defects indicating the potential presence of residual myocardial viability.
Nuclear Medicine Communications 06/2001; 22(6):663-71. · 1.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) is considered to be a very useful adjunct to anatomic imaging techniques and is now primarily used for oncological indications. These indications include diagnosis, staging, and therapy monitoring. In this review, we discuss the articles in which FDG-PET is clinically used for monitoring therapy in breast cancer, lymphomas and gliomas. It is found that the amount of FDG uptake strongly correlates with response to therapy in breast cancer, lymphomas, and gliomas; a decrease in FDG uptake after therapy indicates a positive response to therapy. However, this conclusion is based on small patient numbers, whereas the exact response mechanism is still unknown. Therefore, more studies in comparable patient groups are required to achieve a better understanding of FDG uptake patterns after therapy. Part IIIb deals with lung, and head and neck cancer, hepatocellular and colorectal tumours, and sarcoma.
Journal of Cancer Research and Clinical Oncology 06/2001; 127(5):269-77. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) is considered to be a very useful adjunct to anatomic imaging techniques and is now primarily used for oncological indications. These indications include diagnosis, staging, and therapy monitoring. In this review, we discuss the articles in which FDG-PET is clinically used for monitoring therapy in lung and colorectal tumours, head and neck cancer, sarcoma, and hepatocellular carcinoma. It is found that the amount of FDG uptake strongly correlates with response to therapy: a decrease in FDG uptake after therapy indicates a positive response to therapy. However, this conclusion is based on small numbers of patients, whereas the exact response mechanism is still unknown. Moreover, in these case series, the interval between tumour therapy and FDG-PET, as well as the method of quantification, SUV or tumour-to-non-tumour ratios, differ per study. Finally, dynamic imaging is a recommended technique by some authors, but it is not a standard technique in clinical practice to evaluate tumour therapy. Therefore, further study is required which has to deal with these major issues before it is possible to draw definite conclusions.
Journal of Cancer Research and Clinical Oncology 06/2001; 127(5):278-85. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study compared the possibilities and limitations of 99mTc-labeled synthetic peptides derived from two human antimicrobial peptides, namely, ubiquicidin (UBI) and lactoferrin (hLF), for the scintigraphic detection of bacterial and fungal infections in mice and rabbits. The rationale of our approach was that selected peptides accumulate in infected areas but not in sterile inflammatory lesions, because they bind preferentially to microorganisms. 99mTc-labeled human neutrophil peptides (defensins), ciprofloxacin, and human polyclonal IgG were included as control agents.
99mTc-labeled peptides and control agents were injected intravenously into animals that had been injected intramuscularly 18 h earlier with multidrug-resistant Staphylococcus aureus, Klebsiella pneumoniae, or fluconazole-resistant Candida albicans. Sterile inflammatory sites were induced by the injection of heat-killed microorganisms or lipopolysaccharide (LPS) into the thigh muscle. Up to 4 h after injection, the accumulation of 99mTc-labeled compounds in the infected/inflamed thigh muscles was determined using scintigraphic techniques and radioactivity counts in dissected tissues.
Scintigraphy revealed that 99mTc-labeled peptides UBI 29-41, UBI 18-35, UBI 31-38, hLF 1-11, and defensins, which showed preferential in vitro binding to microorganisms in a former study, accumulated at a significantly higher rate (P < 0.01) in bacterial and C. albicans infections in mice and rabbits than in inflamed tissues induced by heat-killed microorganisms or by LPS. No significant difference in the accumulation of 99mTc-labeled ciprofloxacin was observed between infected and sterile inflamed thigh muscles in mice.
99mTc-labeled antimicrobial peptides UBI 29-41, UBI 18-35, UBI 31-38, hLF 1-11, and defensins accumulate significantly in tissues infected with gram-positive and gram-negative bacteria and C. albicans. Significantly lower (P < 0.01) accumulation of these peptides occurs in sterile inflamed tissues. These data indicate that the peptides preferentially tag microorganisms at the site of infection, which is in agreement with their preferential binding to the microorganisms in vitro and in vivo. 99mTc-labeled ciprofloxacin does not distinguish between infections and sterile inflammatory lesions, which implies that its specificity for the detection of bacterial infections is not warranted.
Journal of Nuclear Medicine 06/2001; 42(5):788-94. · 5.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The differentiation of residual viability from necrotic myocardium in patients with a prior myocardial infarction is important when deciding whether revascularization is indicated. Myocardial viability can be assessed by studying perfusion and regional wall motion. Gated single-photon emission tomography (SPET) imaging allows the simultaneous assessment of perfusion and function through a single study. The aim of this study was to analyse the concordance between wall motion score derived by gated SPET and by contrast ventriculography. Furthermore, the agreement between myocardial perfusion and regional myocardial wall motion was analysed for both techniques. We studied a homogeneous group of 26 consecutive patients with a prior myocardial infarction, using both gated technetium-99m tetrofosmin SPET and contrast ventriculography. A seven-segment model of the left ventricle was employed to score regional myocardial wall motion on images obtained with gated SPET and contrast ventriculography using a four-point scale. Contrast ventriculography was performed within 2 weeks of the gated SPET study. Prevalence of abnormal wall motion (akinetic or dyskinetic) was 24/182 (13%) for gated SPET and 25/182 (14%) for contrast ventriculography (P = NS). There was a high agreement (80%) in wall motion score between gated SPET and contrast ventriculography (kappa = 0.67, P < 0.001). The agreement was better in segments with normal or mild to moderate hypoperfusion (82%, kappa = 0.69) than in those with severe hypoperfusion (67%, kappa = 0.56). The agreement between myocardial perfusion and myocardial wall motion was 89% (162/182), kappa = 0.57, for gated SPET and 80% (145/182), kappa = 0.21, for contrast ventriculography. The relation between the summed wall motion scores per patient on gated SPET and contrast ventriculography was excellent (y = 0.81x + 2.9, r = 0.82, P < 0.01). Thirteen (43%) out of 30 segments with severely diminished or no myocardial perfusion showed normal or hypokinetic wall motion on gated SPET, suggesting residual myocardial viability in malperfused regions. Our results suggest that gated SPET imaging is a reliable tool for the assessment of regional wall motion in post-myocardial infarction patients. Furthermore, in patients with a previous myocardial infarction, gated SPET imaging has the potential to detect preserved wall motion in regions with fixed perfusion defects, which might be indicative of residual myocardial viability.
European Journal of Nuclear Medicine 05/2001; 28(4):514-21.
[Show abstract][Hide abstract] ABSTRACT: The presence of a left bundle branch block (LBBB) pattern on the electrocardiogram may frequently lead to perfusion defects in the septum not necessarily due to ischemic heart disease, but probably due to abnormal septal wall motion. The introduction of gated single photon emission computed tomography (SPECT) allows the evaluation of myocardial perfusion and function in one study. Accordingly, we analysed perfusion and function and the relation between perfusion and regional function in the septal region in patients with a LBBB without evidence of a previously sustained myocardial infarction.
We selected 37 patients with a LBBB without a history of a previous myocardial infarction, which was confirmed by echocardiography and/or coronary angiography. All patients underwent technetium-99m tetrofosmin gated SPECT myocardial imaging. Twelve control patients with a low likelihood of coronary artery disease and a normal technetium-99m tetrofosmin gated SPECT myocardial perfusion scintigram were selected as a reference population. The left ventricle (LV) was divided into 18 segments, which were scored for perfusion and function (wall motion and wall thickening) on a 4-point scale.
The average LV end-diastolic volume was higher and the average LV ejection fraction was lower in patients with LBBB as compared to controls (142+/-90 vs. 81+/-18 ml, and 48+/-19 vs 62+/-7%, p=0.03 and p=0.02, respectively). Not only in the septum, but also in the other segments, reduced myocardial perfusion and abnormal wall motion/wall thickening was observed in the patients with LBBB (p<0.0001 vs controls). Patients with LBBB showed no correlation between perfusion and function in the septum, and between perfusion in septum and global LV function (r=0.21, p=0.2; r=0.10, p=0.6, respectively). Conversely, a good correlation was found between perfusion and function, either regional or global, in the remote segments (both r=0.79, p<0.0001).
We conclude that patients with LBBB without a previous myocardial infarction show cardiomyopathic changes with perfusion and wall motion abnormalities, involving the entire left ventricle. The severity of diminished septal perfusion is not directly associated with the severity of septal wall motion abnormalities or global LV function. However, in the myocardial segments remote from the septum, reduced perfusion is closely associated with functional abnormalities.
The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 04/2001; 45(1):108-14.
[Show abstract][Hide abstract] ABSTRACT: Gated single-photon emission computed tomography (gated SPECT) myocardial perfusion imaging allows the analysis of left ventricular (LV) perfusion and function during the same acquisition.
Gated SPECT provides additional information to myocardial perfusion, which improves test specificity in patients with known or suspected coronary artery disease and hence diminishes the amount of borderline diagnosis. Because gated SPECT provides reliable information on LV ejection fraction and LV volumes, it is also a valuable tool in risk stratification. In addition, from gated SPECT, images can be reconstructed from which wall motion can be assessed showing a good correlation with wall motion assessed by accepted imaging modalities as echocardiography, magnetic resonance imaging, and contrast angiography. In the future wall motion analysis from gated SPECT may also be used for revascularization stratification.
Gated SPECT gives important additional information beyond myocardial perfusion imaging alone, which could have major clinical implications for optimal patient management.
American Heart Journal 04/2001; 141(3):383-90. · 4.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since human lactoferrin (hLF) binds to bacterial products through its highly positively charged N terminus, we investigated which of the two cationic domains is involved in its bactericidal activity. The results revealed that hLF lacking the first three residues (hLF(-3N)) was less efficient than hLF in killing of antibiotic-resistant Staphylococcus aureus, Listeria monocytogenes, and Klebsiella pneumoniae. Both hLF preparations failed to kill Escherichia coli O54. In addition, hLF(-3N) was less effective than hLF in reducing the number of viable bacteria in mice infected with antibiotic-resistant S. aureus and K. pneumoniae. Studies with synthetic peptides corresponding to the first 11 N-terminal amino acids, designated hLF(1-11), and fragments thereof demonstrated that peptides lacking the first three N-terminal residues are less effective than hLF(1-11) in killing of bacteria. Furthermore, a peptide corresponding to residues 21 to 31, which comprises the second cationic domain, was less effective than hLF(1-11) in killing of bacteria in vitro and in mice having an infection with antibiotic-resistant S. aureus or K. pneumoniae. Using fluorescent probes, we found that bactericidal hLF peptides, but not nonbactericidal peptides, caused an increase of the membrane permeability. In addition, hLF killed the various bacteria, most probably by inducing intracellular changes in these bacteria without affecting the membrane permeability. Together, hLF and peptides derived from its N terminus are highly effective against infections with antibiotic-resistant S. aureus and K. pneumoniae, and the first two arginines play an essential role in this activity.
Infection and Immunity 04/2001; 69(3):1469-76. · 4.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bone scintigraphy continues to be one of the most commonly performed procedures in nuclear medicine. The radionuclide bone scan remains an excellent modality to detect metastatic disease in patients suffering from primary malignancies. This article reviews a number of aspects of bone scintigraphy such as bone physiology, radiopharmaceuticals and uptake mechanisms. As 99mTc labelled bis(di)phosphonates are the most frequently used this article is centred around these imaging agents. In addition to diagnostic bone scintigraphy the use of various bone seeking agents has been extended to the palliative treatment of bone metastases. In this context the radiobiological characteristics of various radionuclides as 89Sr, 32p, 153Sm, 186Re and 117Sn is elucidated. In addition, the clinical efficacy for pain killing of these radionuclides is elucidated on the basis of the radiation properties of these agents. It is concluded that 89Sr and 186Re are presently the radionuclides of choice. The latter agent has a slight advantage as its imaging photons enable individual dosimetry, resulting in an optimosed application scheme.
The quarterly journal of nuclear medicine: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR) 04/2001; 45(1):18-26.