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

In order to investigate [¹¹C]nicotine binding and metabolism in the living human brain by PET, routine protocols were developed for the preparation and purification of (S)- and (R)-[¹¹C]nicotine and the metabolite ($\text{R}\text{S}$)-[¹¹C]cotinine. (S)- and (R)-[¹¹C]nicotine were prepared by N-methylation with [¹¹C]methyl iodide of the appropriate secondary amine, which was liberated in situ by 2,2,6,6,-tetramethylpiperidine (TMP) from its corresponding biscamsylate-salt. ($\text{R}\text{S}$)-[¹¹C]Cotinine was prepared by N-methylation of the amide precursor using tetrabutylammonium hydroxide as a phase transfer catalyst. Straight-phase semipreparative HPLC was in all purifications found to be superior to reversed-phase since the contamination by the norcompounds was eliminated. Reaction in acetonitrile for both (S)- and (R)-[¹¹C]nicotine (5 min, 130 °C) and ($\text{R}\text{S}$)-[¹¹C]cotinine (l min, 80 °C) with subsequent straight-phase HPLC purification resulted in 35–45% radiochemical yield (from EOB and decay-corrected) with a total synthesis time of 30–35 min, a specific radioactivity of 1000–1500 Ci/mmol (37–55 GBq/μmol, EOS) and a radiochemical purity >99%. The uptake and distribution of these tracers in the human brain was studied in healthy volunteers by PET. The metabolite ($\text{R}\text{S}$)-[¹¹C]cotinine did not cross the blood-brain barrier to any significant degree. The amount of the total radioactivity representing (S)-[¹¹C]nicotine measured in plasma by HPLC was 75% at 4 min and 25% at 50 min.

[³H]CGP-12177, a non-selective β-adrenoceptor antagonist, and [³H]CGP-26505, a β₁-selective β-adrenoceptor antagonist, were intravenously administered to rats. 94–97% of the injected radioactivity disappeared from plasma with $\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ 0.2 and 0.5 min. Total/non-specific binding ratios of 5.4 and 6.9 (CGP-12177) or 2.0 and 2.8 (CGP-26505) were maintained in heart and lung from 10 to 40 min post-injection. Labelled plasma metabolites appeared after >20 min (CGP-12177) or within 2 min (CGP-26505). No metabolites were found in the heart. CGP-12177 binds to blood cells, but CGP-26505 does not. CGP-12177 can be used for PET imaging of total (β₁, and β₂) adrenoceptors in the heart and lung of experimental animals, but CGP-26505 is less suitable for in vivo analysis of the β₁-subpopulation.

Traditionally, when preparing ^99mTc-labeled radiopharmaceuticals, [^99mTc]pertechnetate is added to the entire contents of a vial of reagent kit, and patient doses are subsequently withdrawn from the vial. This technique of compounding can be potentially wasteful for two reasons: (1) once reconstituted with ^99mTc, most reagent kits have a relatively short shelf-life, and thus the entire contents may not be used before expiration and (2) due to a need to conserve radioactivity in many hospitals, enough [^99mTc]pertechnetate is added to the reagent kit in order to retrieve only 1–2 patient doses, even though adequate chemicals (ligand, reducing agent, etc.) are present in the reagent kit to supply as many as 5–10 doses. Hence, a method for optimizing the efficient use of reagent kits would be desirable. The purpose of this study was to determine the feasibility of unit-dosing non-radioactive reagent kits and storing these cold unit doses (CUDs) for eventual labeling with ^99mTc. To evaluate this concept, unit doses were prepared from reagent kits of medronate (MDP) and pentetate (DTPA). The specific variables studied in this research were the effects of storage time, storage temperature and reconstitution volume (dilution) on the unit doses. These effects were monitored by measuring the radiochemical and biodistribution properties of the unit doses following their final reconstitution with [^99mTc]pertechnetate. The labeling efficiency was determined using instant thin layer chromatography (ITLC), and the biodistribution patterns of these radiolabeled CUDs were studied in mice. The results showed that MDP- and DTPA-CUDs stored at −18 °C retained the properties which resulted in acceptable radiochemical purity and biodistribution in mice for as long as 30 days. On the other hand, the radiochemical purity of MDP and DTPA unit doses stored at 25 °C deteriorated rapidly. Mean radiochemical purities as low as 0.58–19.4% were observed on day 30. Altered biodistributions were observed in a manner consistent with the decreased labeling efficiencies. The CUDs of lower dilution (3 mL) appeared to be more stable than the CUDs of higher dilution (10 mL). However, the effect of reconstitution volume was much less significant than the temperature effect on the CUDs. In conclusion, the concept of unit-dosing non-radioactive reagent kits appears to provide an efficient and cost-saving method for preparing infrequent and emergency radiopharmaceutical doses. The study also showed that the storage temperature of these unit doses is critical to the success of the procedure. The volume of reconstitution has a minimal impact on the stability of CUDs if stored at the appropriate temperature.

Tetramethylpropyleneamine oxime (TMPAO) was synthesized and complexed to ^99mTc. ^99mTc-TMPAO samples, when challenged with reduced glutathione (GSH), were shown to have two GSH sensitive components, similar to a mixture of d,l and meso ^99mTc-HMPAO. One component had a GSH-induced second-order dissociation rate constant (K₂) similar to ^99mTc-meso-HMPAO. Despite the presence of a large fraction of this component in these samples, brain uptake and autoradiographic studies with ^99mTc-TMPAO were equivalent to ^99mTc-d,l-HMPAO suggesting that both the d,l and meso ^99mTc-TMPAO isomers are efficiently trapped in brain.

A monoclonal antibody, C-215, against colon cancer, was internally labelled with [⁷⁵Se]methionine. The biodistribution was studied in tumour-bearing nude mice and compared with the biodistribution of [¹³¹I]C-215. The tissue uptake was divided into three parts: antibody bound to the antigen, antibody in the extracellular space and uptake of the released radionuclide. [⁷⁵Se]C-215 showed a greater amount of antigen-bound antibody in the tumour, but also a greater unspecific uptake both in tumour and normal tissue.

We have designed and synthesized two radioiodinated analogs of hexadecylphosphocholine in order to evaluate their tumor imaging potential. 12-(m[¹²⁵I]iodophenyl)dodecyl phosphocholine (NM-324) and hexadecyl-2-[N,N-dimethyl-N-(m[¹²⁵I]iodobenzyl-ammonium]ethyl phosphate (NM-326) demonstrated the ability of such compounds to localize in and thereby visualize the Walker 256 tumor in rats. However, the tumor avidity of NM-324 was far superior to NM-326. In addition, NM-324 showed excellent tumor localization in athymic mice bearing subcutaneous human tumors.

Diaminedithiols (DADT) are known to form neutral-lipophilic complexes with ^99mTc in aqueous solutions, where they are readily formed in high yields and demonstrate excellent stability. A new triaminedithiol (TADT) ligand was synthesized, characterized and shown to form a neutral-lipophilic ^99mTc-chelate. The biodistribution of this ^99mTc chelate in rats showed that its uptake in brain or heart following i.v. injection of the ^99mTc chelate was low, but activity taken up was retained over a long period of time. The in vivo and in vitro properties of this chelate indicate the possibility that chemical modification of this TADT ligand may produce ligand systems that form ^99mTc chelates with suitable diagnostic properties.

The interaction of ethanol (EtOH), prolactin (Prl) and luteinizing hormone (LH) was examined in two studies. In the first study, adult male C57 B1/6J mice were given a single intraperitoneal injection of either vehicle or Prl at 5, 10 and 20 mg/kg and a significant dose-related suppression of ethanol consumption was found. This injection did not cause any differences in food intake or body weight. Additionally, a 5 mg/kg dose of Prl was also given to adult male Long Evans Hooded rats and, similarly, there was a significant suppression of ethanol consumption. In a second study, when rats were given a free choice between water and 5% EtOH, three subgroups were found regarding the amount of EtOH consumption: low, medium and high. After 2 weeks of free choice, hypothalamic, but not serum Prl and LH levels, were significantly increased in EtOH-imbibing groups compared to controls. These findings suggest important interactions between EtOH consumption and ambient levels of Prl and LH.

^99mTc-erythromycin (E) and ^99mTc-streptomycin sulphate (SS) were prepared with >98% labelling efficiency. The labels were stable up to 24 h of testing, using ITLC-SG strips and acetone and saline as solvents. The biodistributions of both radiopharmaceuticals versus ⁶⁷Ga-citrate were studied in mice with turpentine-induced abscesses at 6 days post-induction. The mice were sacrificed at 1, 3 and 6 h post-injection of 15 MBq of ^99mTc-E or ^99mTc-SS. Mice injected with ⁶⁷Ga-citrate were sacrificed at 4 and 24 h. The maximum abscess-to-muscle ratios obtained by biodistribution studies were 2.36 ± 1.04 (6 h), 2.38 ± 0.38 (6 h) and 4.76 ± 2.04 (4 h) with ^99mTc-E, ^99mTc-SS and ⁶⁷Ga-citrate, respectively. The maximum abscess-to-contralateral tissue ratios by ROIs over respective areas on scintigrams were 2.38 ± 0.16 (6 h), 3.21 ±0.14 (3 h) and 3.24 ± 0.92 (24 h) for Tc-E, ^99mTc-SS and ⁶⁷Ga-citrate, respectively. The uptake mechanism might be infiltration into interstitial space due to increased capillary permeability.