International Journal of Radiation Applications and Instrumentation. Part B. Nuclear Medicine and Biology最新文献

Different derivatives of MAG₃ carrying amino acids such as d- or l-alanine, d-serine, d-2-aminobutyric acid, d-valine or d-phenylglycine were synthesized and their ^99mTc-complexes were evaluated in mice and a baboon. The efficiency of renal handling of the examined ^99mTc-complexes is influenced not only by their lipophilicity but also to a great extent by their configuration and the site of substitution. The renal excretion characteristics of ^99mTc-MAGAG-DA are superior to those of ^99mTc-MAG₃ and the studied ^99mTc-complexes in both animal species.

In an attempt to improve the renal handling of ^99mTc-MAG₃ and to evaluate the effect of derivatization we have synthesized different derivatives of MAG₃ in which one or more glycyl groups are replaced by other amino acids such as d- or l-alanine, D-serine, D-2-aminobutyric acid, D-valine or D-phenylglycine. Due to the presence of a chiral centre in the ligand core, exchange labelling of each of the MAG₃ derivatives results in the formation of two diastereomeric technetium complexes. These isomers were separated by HPLC and evaluated in mice. Biodistribution in mice indicates that the efficiency of renal handling of the examined ^99mTc-complexes is not only influenced by their lipophilicity but also to a great extent by their configuration. The renal excretion characteristics of isomer dA of ^99mTc-MAGAG in mice are superior to those of all other studied ^99mTc-complexes and also of the reference compound [¹³¹I]Hippuran. The isomers lB of several alanyl derivatives of ^99mTc-MAG₃ exhibit a pronounced renal retention in both mice and baboon. The results of the evaluation in a baboon confirm the superiority of ^99mTc-MAGAG-dA over ^99mTc-MAG₃ and the other studied ^99mTc-complexes.

Radioiodinated (+)−3-Iodo-MK-801 is a high affinity radioligand for the N-methyl-d-aspartate (NMDA) receptor-channel complex. We have demonstrated in vivo localization in the CNS of rat which is stereoselective and blocked by coinjection of unlabeled MK-801. Autoradiography indicates localization in vivo which is in concordance with in vitro autoradiographic studies. These results indicate that radioiodinated (+)−3-Iodo-MK-801 is a useful probe for in vitro and in vivo autoradiographic studies and suggest that radioligands for the NMDA receptor may be developed which will provide in vivo images of receptor distribution in man.

Two methods were investigated for the no-carrier-added synthesis of N-succinimidyl 4-[¹⁸F]fluorobenzoate (S[¹⁸F]FB). The first, an attempted nucleophilic aromatic substitution by [¹⁸F]fluoride on N-succinimidyl 4-nitrobenzoate was unsuccessful. The second method involved three steps; [¹⁸F]fluoride for trimethylammonium substitution on 4-formyl-N,N,N-trimethylanilinium triflate, oxidation to 4-[¹⁸F]fluorobenzoic acid, followed by reaction with N-hydroxysuccinimide and dicyclohexylcarbodiimide to form S[¹⁸F]FB. Total synthesis and purification time was 100 min and the overall radiochemical yield was 25% (decay corrected). A monoclonal antibody F(ab′)₂ fragment could be labeled in 40–60% yield by reaction with S[¹⁸F]FB for 15–20 min. The tissue distribution in normal mice and in vitro tumor binding of the antibody F(ab′)₂ labeled by reaction with S[¹⁸F]FB were comparable to those observed for the fragment after radioiodination using N-succinimidyl 4-[¹²⁵I]iodobenzoate.

Lung scintigraphy using N-isopropyl-p-[¹²³I]iodoamphetamine (IMP) was performed on 26 patients with pulmonary tuberculosis. Early (5 min after injection) and late images (4 h after injection) were obtained with a large-field γ-camera equipped with a digital computer. Lung scintigraphy using [^99mTc]MAA (MAA) was also done. Although early IMP images showed the same findings as [^99mTc]MAA images, a discrepancy between delayed IMP images and [^99mTc]MAA images was seen in some patients. Increment of activities seen in late images was demonstrated in most patients whose chest x-ray findings included exudative inflammatory changes. Uptake and clearance of IMP was considered to be affected by the active phase of pulmonary tuberculosis.

A simplified and efficient procedure for ^99mTc-HMPAO-labelling of leukocytes is described. For this purpose, the pH and concentration of the ^99mTc-HMPAO preparation was modified. Leukocytes were isolated from a 20 mL mixture of patient blood, 5 mL ACD and 0.8 mL methylcellulose after 1 h sedimentation of erythrocytes and centrifugation (at 400 g) of the obtained plasma layer. Simultaneously, ^99mTc-HMPAO was prepared (one single-dose kit for two patients) by adding 2.2 mL ^99mTc-generator eluate and, after 10 min, 0.3 mL of phosphate buffer to lower the pH to 7. The isolated WBCs were then labelled by the addition of 1-1.2 mL of ^99mTc-HMPAO solution and incubated for 20 min. The unbound tracer was then discarded, the labelled WBC washed and finally resuspended in autologous cell-free plasma. Leukocytes labelled by this procedure were used for scintigraphic localization of inflammatory lesions and abscesses in the gastro-intestinal tract.

The labelling efficiency was 60 ± 9%, with a separation yield of 55 ± 11%.

17α-[¹²³I]Iodovinyl-11β-methoxyestradiol was injected into 19 women: group 1 (n = 8), initial evaluation of breast cancer; group 2, (n = 11) postoperative follow-up including 9 patients with bone metastases. The primary tumor (size: 8–10 mm) was visualized by breast tomoscintigraphy in $\text{2}\text{4}$ patients of group 1 with high estrogen receptor concentration (162–445 fmol/mg) and was not detectable in 4 patients with low estrogen receptor concentration (6–32 fmol/mg). Axillary lymph node metastases were detected in 1 patient of group 1 and in 1 patient of group 2. In 4 patients of group 2 with previous primary tumor containing estrogen receptors, MIVE₂ uptake in bone metastases was demonstrated. MIVE₂ scintigraphy is an original, specific and non-invasive method for breast cancer estrogen receptor imaging in primary and in metastatic tumors.

A new ligand, an N-p-iodophenethyl diaminodithiol (DADT-IPE), an anlog of N-isopropyl-p-iodoamphetamine (IMP), was synthesized and subsequently complexed with ^99mTc, using stannous chloride as a reducing agent. Two complexes (a and b) were separated from ^99mTc-DADT-IPE by high performance liquid chromatography (HPLC). Competitive inhibition studies showed that the IC₅₀ value of DADT-IPE (70 μM) was similar to that of IMP (49 μM). Biodistribution studies of one of the complexes [^99mTc-DADT-IPE(a)] in rats showed that 0.65% of the injected dose of the tracer remained in the brain at 5 min after intravenous injection, with 0.53% of the dose remaining in the brain at 60 min post-injection, whereas the corresponding values for the other complex [^99mTc-DADT-IPE(b)] were 0.34% dose in the brain at 5 min and 0.28% dose in the brain at 60 min post-injection. The half-life for clearance of ^99mTc-DADT-IPE(a) from rat brain was found to be more than 5 h. These results suggested that ^99mTc-DADT-IPE(a) has characteristics which are suitable for cerebral perfusion imaging.

Labelled fatty acids have been proposed to explore cardiac metabolism. For the analysis of the external detection curve obtained with 16-iodo 9-hexadecenoic acid (IHA), we developed a mathematical 4-compartment model with compartments 0, 1, 2 and 3 representing vascular IHA, intracellular IHA, esterified forms and iodide, respectively. This model, used here for isolated rat hearts perfused in a recirculating system, is validated by an intracellular analysis, then tested in various metabolic conditions. Thus, the mathematical analysis of the external detection curve gives us numerical data on IHA metabolism, especially the distribution between degradation and storage. Our results confirm the suitability of IHA for assessing myocardial metabolism.

The nitrosyl complexes pentachloronitrosylosmate(II), [OsCl₅(NO)]²⁻, and hydroxytetranitronitrosylosmate(II), [Os(OH)(NO₂)₄(NO)]²⁻, were evaluated as parent species for use on the ¹⁹¹Os-^191mIr generator in an attempt to increase the ^191mIr yield of the generator by providing a direct route to a chemically stable ^191mIr daughter. The uptake of the ¹⁹¹Os-labeled complexes by the inorganic ion-exchangers ZrO₂, SnO₂, PbS, MnO₂ and Al₂O₃ and the organic resin AG MP-1 was measured and prototype generators were prepared using those exchangers that demonstrated greater than 90% uptake of the ¹⁹¹Os-labeled complexes. The ^191mIr(III)-nitrosyl complexes produced subsequent to β⁻ decay of the ¹⁹¹Os-nitrosyl parent complexes were found to undergo secondary chemical reactions to form nitro (NO⁻₂) complexes that were tightly retained on the ion exchanger limiting ^191mIr yield to less than 5%.