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

The expression of cell surface antigens of the spontaneous transplantable M3-murine tumour was studied by means of the monoclonal antibody (MAb) B2C114 which recognizes the human blood group-A carbohydrate antigen. Following radioiodination the MAb retained their immunoreactivity and demonstrated a significantly higher in vitro binding with isolated M3-tumour cells as compared with a control antibody. B2C114 revealed 10⁶ antigenic sites per cell, with a constant affinity of 5.1 × 10⁹/M. Biodistribution studies showed that B2C114 discriminated between malignant tumour and mouse normal tissues. Radioimmunodetection of Balb/c mice bearing s.c. M3-tumour showed that tumour was specifically defined without substraction 1 day after injection of the radiolabelled antibody.

We present the original synthesis of two halogenated analogues of the diphenyl piperazine GBR, bromo-GBR and iodo-GBR, as new dopamine uptake carrier ligands. The derivatives were purified by HPLC and chemically characterized. Bromo-GBR and iodo-GBR are potent inhibitors of [³H]GBR 12935 binding to rat striatal membrane, with K_i values of 116 and 113 nM, respectively. We prepared iodo-GBR labeled with iodide-125 from the brominated derivative and concluded that [¹²³I]iodo-GBR could be a potential tool to explore the in vivo dopamine uptake carrier.

An improved method of direct labeling MAbs with ^99mTc is described. Two murine monoclonal antibodies, designated Lym-1 and B72.3, have been successfully labeled with ^99mTc in 0.1 M borate buffer at pH 9.3. The choice of buffer and pH was essential for obtaining a radiolabeling yield ⩾98%. In vitro studies demonstrated that the radiolabeled antibodies were stable and retained their immunoreactivity. Imaging and biodistribution studies using Raji and LS174T human tumor-bearing nude mice demonstrated a significant tumor uptake at 24-h post-injection of ^99mTc-labeled MAbs. This improved labeling method showed better stability than those of previously published methods and resulted in significant improvement in the uptake of antibody in tumor. External images at 24 h post-injection revealed clearly visible tumors demonstrating the benefit of this method for tumor immunoscintigraphy.

We have prepared eight fluorine-substituted corticosteroids representing ligands selective for Type I and Type II corticosteroid receptor subtypes as potential imaging agents for corticosteroid receptor-containing regions of the brain. Receptor binding affinity assays show that fluorine substitution for hydroxyl or hydrogen in these steroids generally results in some reduction in affinity, with the result that the absolute affinity of these fluorine-substituted ligands for receptor is less than that typical for steroid hormones that show receptor-based, target selective uptake in vivo. Five of these compounds were prepared in fluorine-18 labeled form by a simple sulfonate ester displacement reaction, and their tissue distribution was studied in the adrenalectomized rat. There is no selective accumulation nor selective retention of the Type I selective corticosteroids (¹⁸F-RU 26752, 21-[¹⁸F]fluoroprogesterone, 21-[¹⁸F]fluoro-11β-hydroxyprogesterone) in either the brain, or other target tissues (pituitary, kidney, liver). The Type II selective corticosteroids (¹⁸F-RU 28362, ¹⁸F-triamcinolone acetonide) show uptake into the hippocampus which can be partially blocked by a competing ligand; in target tissues outside the brain, the blocking is more complete. All of the ¹⁸F-labeled compounds show considerable defluorination, evident as high bone activity levels. These results, coupled with earlier findings in the literature, suggest that radiolabeled corticosteroid receptor ligands with both greater metabolic stability and higher receptor binding affinity and selectivity are needed for imaging corticosteroid receptors in the hippocampus.

THM₂BED [N,N,N′,N′-tetrakis-(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine] is a new hexadentate ligand which has been synthesized and complexed with gallium isotopes. A conditional stability constant of 22.3 and a pM value of 20.7 have been determined for GaTHM₂BED at physiological pH. Hexachelated and pentachelated complexes of GaTHM₂BED have been isolated via preparatory HPLC and evaluated individually. The hexachelated isomer of ⁶⁸GaTHM₂BED clears slowly from the myocardium of rats and at 1 h post-injection the heart-to-blood ratio is 1.65. The data ratio indicates that this radiotracer may be capable of measuring blood flow in the heart. The ability of ⁶⁸GaTHM₂BED to delineate myocardial tissue in a dog has been evaluated and good images were obtained using hexachelated ⁶⁸GaTHM₂BED. There is evidence that this complex penetrates the blood-brain barrier.

This report, based on the past experience of European centres, offers practical guidance on the chemistry and biochemistry of PET radioligands used for the in vivo imaging of dopamine receptors and re-uptake sites. It mainly summarizes methods for the preparation of D1 and D2 receptor ligands labelled with positron-emitting radioisotopes. Some of these ligands (¹¹C-labelled SCH23390, raclopride and nomifensine, ¹⁸F-labelled butyrophenones, [⁷⁶Br]bromolisuride), which have been found useful in PET clinical investigations, have been emphasized. This report is intended as an introduction and guideline for new PET-groups who want to start research in the dopaminergic neurotransmission imaging field.

The distribution and retention of selenate and selenite in C57L/J mice was investigated using ⁷⁵Se radioisotope. The comparison is made with the normal distribution of the element determined by using radioisotope-induced x-ray fluorescence, RIXRF methods. The distribution of the two oxidation states measured as activity of ⁷⁵Se was almost identical but differed from the normal trace elemental profile, TEP. The excretion rates of the two selenium species in the initial phase are different with more selenate being excreted than selenite in the first 2 days. It was found that the wholebody excretion rates followed a pure first-order pattern this was not true for the individual organs of the animals.

The ¹³N-labeled opioid tetrapeptide, Tyr-D-Met(O)-Phe-Gly-[¹³N]NH₂ (SD-62), was synthesized by amidation of its activated p-nitrophenol ester with [¹³N]ammonia (total synthesis time: 25 min, radiochemical yield: 48%). When injected intravenously into mice, [¹³N]SD-62 was taken up by the brain and this uptake was blocked by naloxone. In addition, the time course of changes in brain radioactivity paralleled that of the analgesic activity of this compound, suggesting that SD-62 underwent binding to brain opioid receptors. Thus, [¹³N]SD-62 appears to hold some promise for use as a radiopharmaceutical for in vivo studies of opioid peptide behavior, using positron emission tomography.

The synthesis, radiochemical analysis and biological characteristics of some 1,8-diamine-3,6-dithiaoctane derivatives labelled with Tc-99m are reported. Analysis by HPLC shows that most of the ^99mTc-chelates are multicomponent. Furthermore, almost all ^99mTc-complexes isolated by HPLC are lipophilic and stable in vitro. The biodistributions of the most lipophilic of these complexes were evaluated in mice. The N-morpholinylethyl and N,N'′-bisalicylyl derivatives of 1,8-diamine-3,6-dithiaoctane yielded ^99mTc-complexes which exhibit considerable uptake and retention in organs of interest, such as the heart and the brain.

^99mTc-Complexes of oxine (ox), thiooxine (tox) and 8-hydroxy-5-quinolinesulphonic acid (HQS) were prepared by ligand exchange of ^99mTcNCl₄⁻ and by stannous and dithionite reduction of ^99mTcO₄⁻. HPLC studies showed that the ^99mTcN-tox preparation was almost pure TcN(tox)₂. ^99mTc(Sn)-ox yielded a number of peaks upon HPLC with the major peak being identified as TcO(ox)₂Cl. No other Tc-complexes responsible for other chromatographic peaks were identified. Biodistribution studies in mice showed that all complexes except ^99mTc-HQS were cleared essentially by the hepatobiliary pathway. The ^99mTc-HQS preparations showed increased renal clearance due to the increased aqueous solubility of the complexes resulting from the presence of the sulphonate group on the quinoline ring.