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

Kits for direct labeling of IgG with ^99mTc were used without modification for the preparation of [⁶⁷Cu]IgG. The IgG was pre-treated to generate thiolate groups which would bind ⁶⁷Cu. The direct labeling of reduced IgG with ⁶⁷Cu was highly efficient, resulting in approx. 95% ⁶⁷Cu binding. Non-reduced IgG (negative control) had labeling efficiencies of less than 10%. IgG pre-exposed to Cu(II) had reduced amounts of ^99mTc bound to it. The results demonstrate a direct relationship between copper- and ^99mTc-binding sites in IgG.

In order to investigate the metastatic potential of tumors in vivo by measuring hyaluronic acid metabolism, C57BL/6 mice with B16 melanoma variants and C3H/He mice with FM3A tumor variants were evaluated using N-[¹⁸F]fluoroacetyl-d-glucosamine (¹⁸F-GlcNFAc). The uptake of ¹⁸F-GlcNFAc was slightly higher (P < 0.05) in B16-F10 tumors (high metastatic potential) than in B16-F1 (low metastatic potential). Analysis of metabolites showed that acid-insoluble fraction was the largest one in the liver by 60 min, whereas in the tumors, phosphates fraction was the major metabolite. Slower metabolism in tumors was suggested, and it may be one of the reasons for the difficulty of detecting the characteristics of their hyaluronic acid synthesis. ¹⁸F-GlcNFAc uptake by FM3A variants showed no significant correlation with their metastatic potential. In addition, N-acetyl-d-[l-¹⁴C]glucosamine, 2-deoxy-d-[l-¹⁴C]glucose and [6-³H]thymidine failed to demonstrate any difference between tumors' metastatic variants in vivo.

Radioiodinated spiperone is of interest for dopamine (DA) receptor studies in the living human brain by single photon emission computed tomography (SPECT). Stimulated by data obtained with [¹¹C]-N-methyl-spiperone we synthesized 4-[¹²³I]iodospiperone and investigated the in vitro binding characteristics of this ligand to the striatal membrane of the rat and the in vivo distribution over various rat brain regions. The in vitro binding experiments showed that this radioligand displays about 10 times less affinity for the DA receptor than spiperone and specific binding, as shown with [³H]spiperone, was not observed. Displacement by butaclamol was not observed. The in vivo studies demonstrated that both 4-[¹²³I]iodospiperone and [³H]spiperone concentrate in striatal tissue, respectively, 1.9 and 3.5 times as high as in cerebellar tissue.

Haloperidol pretreatment largely prevented this accumulation. In view of the obtained target-to-non-target ratios we believe, however, that this accumulation in brain areas rich in DA-receptors does not offer prospects for clinical receptor imaging with SPECT.

Two different methods were evaluated for incorporating [¹²⁵I]cholesteryl iopanoate ([¹²⁵I]CI), a non-hydrolyzable cholesteryl ester analog, into LDL. The first procedure was an organic solvent delipidation-reconstitution procedure (R[¹²⁵I-CI]LDL) while the second involved incubation of detergent (Tween-20)-solubilized [¹²⁵I]CI with whole plasma (D[¹²⁵I-CI]LDL). R[¹²⁵I-CI]LDL behaved similar to native LDL in vitro, but was markedly different in vivo, apparently due to a heterogeneity in particle size. D[¹²⁵I-CI]LDL, however, was metabolized normally both in vitro and in vivo. These results, combined with the residualizing nature of [¹²⁵I]CI, demonstrate that D[¹²⁵I-CI]LDL is appropriate for tracing LDL uptake in vivo.

A simple procedure for the preparation of ^99mTc—carbonyl complexes of dithiocarbamates in high yield and radiochemical purity has been developed and used for the preparation of ^99mTc—carbonyl complexes of bis(2-hydroxyethyl)dithiocarbamate and bis(2-hydroxypropyl)dithiocarbamate. These complexes were found to be extremely stable and their biological behaviour was studied in mice and compared to that of the ^99mTcN- and the ^99mTc-complexes [prepared by dithionite (dit) reduction] of the same ligands. The carbonyl complexes were found to be efficient hepatobiliary agents and cleared more rapidly than the corresponding ^99mTcN- and ^99mTc(dit)-complexes.

Various radionuclide-ligand complexes were encapsulated in liposomes and their accumulations in tumors were studied. Increased tumor accumulation was observed with every complex in the liposome-encapsulated form. However, different accumulation levels were registered for the various radionuclides even though they were all delivered using a similar liposome formulation. Though the liposomes remained intact in the circulation, they were degraded in the tumor, liver and spleen eventually. Thus, this suggests that tumor accumulation of liposome-encapsulated radionuclides is dependent on not only the in vivo behavior of the liposomes themselves, but also the characteristics of nuclide—ligand complexes after their release from liposomes. A correct choice of radionuclides and ligands for encapsulation in liposomes would enable excellent tumor-imaging agents to be achieved.

Monoclonal antibodies can be labelled with technetium-99m by prereduction of the antibody with 2-mercaptoethanol, then reduction of pertechnetate with an aliquot of a stannous kit, resulting in > 97% labelling without the need for further purification. The present work shows that equally high labelling can be obtained with a variety of weak ligands and that the optimum quantity of stannous chloride is 2–4 μg. Although the label was stable to challenge with excess DTPA, cysteine was able to remove a portion of the label. We have also shown that this technique works with the IgG_2a isotype in addition to the previously reported IgG₁ isotype. This approach is simple, convenient and reproducible, and warrants further clinical evaluation.

The subcellular distribution of radiocopper in the brain and liver of rats has been determined following i.v. administration of Cu-PTSM, pyruvaldehyde bis(N⁴-methylthiosemicarbazonato)copper(II), labeled with copper-67. Homogenized tissue samples were separated by differential centrifugation into four subcellular fractions: (I) cell membrane + nuclei; (II) mitochondria; (III) microsomes; and (IV) cell cytosol. Upon sacrifice at 10 min post-Cu-PTSM injection, brain fractions, I, II, III and IV contain 35 ± 12, 11 ± 3, 2.8 ± 1.3 and 51 ± 7% of brain activity, respectively (n = 4). In animals sacrificed 24 h post-injection the subcellular fractions of brain tissue show little change from the radiocopper distribution seen at 10 min post-injection, although the mitochondrial fraction may contain slightly more tracer and the cytosolic fraction slightly less (I, 40 ± 10%; II, 18 ± 5%; III, 3.4 ± 1.5%; and IV, 38 ± 5%; n = 5). Subcellular fractions I, II, III and IV of liver contain 25 ± 5, 12 ± 3, 17 ± 4 and 46 ± 6% of ⁶⁷Cu tracer in animals sacrificed 10 min post-Cu-PTSM injection. An identical subcellular distribution of ⁶⁷Cu, was found in the liver following i.v. administration of ionic radiocopper (as Cu-citrate). The liver and brain cytosolic fractions at 10 min post-injection were further separated by Sephadex column chromatography. In liver cytosol, three different radiocopper components with molecular weights of about 140,000, 41,000–46,000 and 10,000–16,000 Da were found. In the brain supernatant fraction, most of the radiocopper was bound to a single low molecular weight cytosolic component (14,000–16,000 Da). These results suggest that the intracellular decomposition of tracer Cu-PTSM may result in the radiocopper entering the normal cellular pools for copper ions.

The potential of seven tracers for the metabolic imaging of tumors by positron emission tomography was studied using five experimental tumor models. The tracers examined were 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG), 2-deoxy-2-[¹⁸F]fluoro-d-galactose (2-[¹⁸F]FdGal) and 2-deoxy-2-[¹⁸F]fluoro-l-fucose (2-[¹⁸F]FdFuc) for investigating energy metabolism. l-[methyl-¹¹C]Methionine ([¹¹C]Met) and 6-[¹⁸F]fluoro-l-fucose (6-[¹⁸F]FFuc) were used for assessing protein and glycoprotein synthesis, while [³H]thymidine ([³ H]Thd) and 2-deoxy-5′-[¹⁸F]fluorouridine ([¹⁸F]FdUrd) were used to investigate nucleic acid metabolism. The highest mean uptake by the five different tumors was found for [³H]Thd, followed in order by [¹⁸F]FDG, [¹¹C]Met, 2-[¹⁸F]FdGal, [¹⁸F]FdUrd, 2-[¹⁸F]FdFuc and 6-[¹⁸F]FFuc. The tumor-to-tissue uptake ratios indicated that the nucleosides, [¹¹C]Met and 6-[¹⁸F]FFuc were better tracers in the brain region. All the tracers except for the fucose analogs were suitable for the thoracic region, while [¹¹C]Thd and [¹⁸ F]FDG were superior in the abdominal region. In comparison with the primary tumor model of Lewis lung carcinoma (3LL), [³H]Thd uptake in the artificial metastatic 3LL model showed the maximum enhancement, followed by [¹⁸F]FDG, [¹¹C]Met and the other tracers. The [¹⁸F]FDG uptake correlated with the [³H]Thd uptake. [¹⁸F]FdUrd, 6-[¹⁸F]FFuc and 2-[¹⁸F]FdGal could be used for distinguishing different types of tumors. The combined use of these radiotracers can possibly allow the assessment of tumor metabolism, and this indicates the viability of tumors.

A significant retention of [¹²⁵I]triiodothyronine ([¹²⁵I]T₃) in the retrobulbar orbital area of mice has been previously shown. The present study was initiated to determine tissue and intracellular localization of the thyroid hormone in the above area which is concerned in human Graves' disease of the thyroid.

Male and female Balb C mice were intravenously injected with 0.1 mL of [¹²⁵I]T₃ (0.2 mCi/gmg). At various time intervals (30 s-10 min) the animals were sacrificed, bled and periorbital tissues were isolated under a dissecting microscope. Three series of samples were prepared: (a) frozen samples for cryomicrotome sections, (b) samples fixed in 10% formaldehyde for paraffin embedded tissues and (c) samples fixed in paraformaldehyde (2%), glutaldehyde (2%) and 0.1 M sodium cacodylate for embedding in Epon-Araldite-DDSA. Sections 5 μ m and 400–600 Å thick for light and electron microscopy, respectively, were coated with Ilford L4 emulsion and exposed for 9–21 days. Light microscope autoradiography demonstrated that [¹²⁵I]T₃ injected intravenously is rapidly transported in the cells of fat tissue of the peribulbar orbital area and tissues with glandular or muscular function: the hormone showed a high affinity for the intra- and extraorbital lacrymal gland cells, the cells of the Harder's gland, those of the sebaceous and meibomian glands of the eye-lids, as well as for local muscular structures. Electron microscope autoradiography showed that radioactivity is already localized inside the cells 30 s after the i.v. injection of [¹²⁵I]T₃ and it is distributed throughout the cytoplasm, with a higher concentration in the vesicles of the Harder's gland cells (rich in lipids and porphyrin), in the endoplasmic reticulum and the mitochondria of the lacrymal glands. 10 min after injection, a shifting of the radioactivity towards the nucleus area was observed. In conclusion, after _vivo injection, the thyroid hormone rapidly penetrates the cells of fat glandular and muscular tissues in the orbital area. Intracellularly, the affinity of the hormone for the secretory vesicles, rough endoplasmic reticulum, mitochondria and nucleus suggest that T₃ could play a role in secretory and metabolic functions of the tissues in the retrobulbar orbital area.