Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours

Purpose For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with ⁹⁰Y is frequently used [⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical ⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide (considered as the gold standard) and the commercially available ¹¹¹In-pentetreotide.Methods The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide, in accordance with the directives of the German radiation protection authorities.Results The range of doses (mGy/MBq ⁹⁰Y-DOTA-Phe¹-Tyr³-octreotide) for kidneys, spleen, liver and tumour masses was 0.6–2.8, 1.5–4.2, 0.3–1.3 and 2.1–29.5 (⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide), respectively, versus 1.3–3.0, 1.8–4.4, 0.2–0.8 and 1.4–19.7 (¹¹¹In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy.Conclusion Compared with ⁸⁶Y-DOTA-Phe¹-Tyr³-octreotide, dosimetry with ¹¹¹In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy.     

226Ra 228Ra 210Pb和210Po在水生生物及食物链中转移规律的探讨

目的 为了解天然放射性核素²²⁶Ra、²²⁸Ra、²¹⁰Pb与²¹⁰Po在水生物及食物链中转移和蓄积情况。方法 定点采集养殖水产品及栖息环境中水与底质沉积物, 按不同的实验需要, 每个鲜样分别剥取肉, 骨(壳),鳞片和胃肠。烹饪样品, 洗净、称重、清炖, 熟后分离出骨(壳),余为食物。样品分别测定²²⁶Ra、²²⁸Ra、²¹⁰Pb和²¹⁰Po含量。数据按统计学要求处理, 配对数据, 作了配对显着性检验。结果 ²²⁶Ra、²²⁸Ra和²¹⁰Pb主要沉积于骨(壳)中, 浓集系数为10²～10³,肉中为10⁰～10².²¹⁰Po主要蓄积在水生物胃肠中, 浓集系数在10²～10⁴,鱼类胃肠与贝类肉中可达10⁴.水产食品烹饪加工过程²²⁶Ra、²²⁸Ra和²¹⁰Pb在食物链中转移不明显, 经配对显着性检验, 差异无显着性(P0.05);然而210Po在淡水鱼类和虾类中转移是明显的, 肉配对检验有非常显着性差别(P<0.01).结论水生物对²²⁶Ra、²²⁸Ra、²¹⁰Pb和²¹⁰Po有很强浓集能力。     

Technetium-99m mercaptoalbumin as a potential substitute for technetium-99m labelled red blood cells

Technetium-99m labelled red blood cells (^99mTc-RBCs) are far superior to ^99mTc-labelled human serum albumin (^99mTc-HSA) for radionuclide ventriculography, but their labelling is more complex, time consuming and risk bearing (in vitro labelling) or suffers from interference by some medications (in vivo labelling). We have now modified HSA by the introduction of mercapto groups with the purpose of preparing stable and practical ^99mTc-mercaptoalbumin with long retention in the vascular system, that could replace ^99mTc-RBCs. HSA was incubated with N-succinimidyl S-acetylthioacetate (SATA) or N-succinimidyl 2,3-di(S-acetylthio) propionate (SATP) to introduce a chain containing one or two protected sulfhydryl groups on some of the lysine amino groups. After purification by size-exclusion chromatography (SEC), the mercapto groups were deprotected by incubation at alkaline pH or by treatment with hydroxylamine. The reaction products were used with or without SEC purification for direct or exchange labelling experiments with ^99mTc at neutral pH. SEC-HPLC was used to determine labelling yields and to isolate pure ^99mTc-mercaptoalbumin. Stable ^99mTc-mercaptoalbumin complexes could be formed in 90%–95% yield after coupling albumin with SATA or SATP in all molar ratios used followed by deacetylation in one of the mentioned conditions. The most favourable results were obtained after reaction of SATA or SATP with HSA in a 25: 1 ratio and deprotection with NH₂OH. The stability of the resulting ^99mTc-mercaptoacetyl-albumin (^99mTc-MAHSA) and ^99mTc-dimercaptopropionyl-albumin (^99mTcDMP-HSA) and their retention in vivo in plasma of mice and rabbits are clearly higher than that of conventional ^99mTc-HSA preparations. ^99mTc-DMP-HSA approaches the behaviour of ¹²⁵I-HSA quite well in both animal species. A preliminary study with ^99mTc-DMP-HSA in a volunteer showed a retention in the vascular compartment almost identical to that of ^99mTc-RBCs and clearly higher than that of a common ^99mTc-HSA preparation. The results indicate that these ^99mTc-mercaptoalbumins and especially ^99mTc-DMP-HSA are very promising as a practical alternative to ^99mTc-RBCs.K.A. Verbeke is a Research Assistant for the Belgian National Fund for Scientific Research     

A novel aluminum vanadate ion exchanger and its use for separation of Ba, In and Ag from Cs, Cd and Au, respectively

A newly designed inorganic ion exchanger, based on aluminum vanadate, has been synthesized and characterized by elemental analysis, spectroscopic tools and powdered X-ray diffraction. The insoluble poorly polycrystalline material is highly stable towards thermal and radiation doses and in various chemical environments. The data of exchange capacities of the solid material for the different alkali and alkaline metal ions determined by batch technique show that the compound can be employed as an ion exchanger. The successful radiochemical separations of the no carrier added daughter nuclides; ^137mBa and ^115mIn from their respective parents present in equilibrium mixtures have been carried out using this material. Elutions of ^137mBa and ^115mIn were performed using 0.0426 mol L⁻¹ ascorbic acid solution and 4.0 mol L⁻¹ HCl, respectively, after sorption of the equilibrated mixtures ¹³⁷Cs–^137mBa at 0.01 mol L⁻¹ HCl medium and ¹¹⁵Cd–^115mIn at pH 7.0, respectively. In another column operation, it has been observed that the separation of gold and silver is possible with the help of the eluents, 0.01% alcoholic solution of Rhodamine-B for gold and 0.5% thiourea solution in 0.1 mol L⁻¹ HClO₄ for silver, respectively, after the sorption of no carrier added onto this material at pH 2.0, at a no carrier added level.     

Cross sections of the Ar(d,α)Cl, Ar(d,α)Cl, and Ar(d,p)Ar nuclear reactions below 8.4 MeV

We have measured the cross section for production of the medically interesting isotope ^34mCl, along with ³⁸Cl and ⁴¹Ar, using deuteron bombardments of ³⁶Ar and ⁴⁰Ar below 8.4 MeV. ALICE/ASH analytical codes were employed to determine the shape of nuclear excitation functions, and experiments were performed using the University of Wisconsin tandem electrostatic accelerator to irradiate thin targets of argon gas.     

Better visualization of a lung tumour with 99mTc-DPD than with 99mTc-glucoheptonate or 67Ga-citrate

A case of a squamous cell lung carcinoma detected with ^99mTc-DPD, ⁶⁷Ga-citrate and ^99mTc-glucoheptonate (GH) is reported. The highest uptake was seen with DPD and the lowest with ⁶⁷Ga. Emission-computed tomography was very useful in DPD imaging but gave less new information in GH and ⁶⁷Ga studies in comparison to traditional planar imaging. The patient had been given both irradiation and chemotherapy, which might be the cause of good accumulation of DPD and rather poor accumulation of GH and ⁶⁷Ga.     

New cross-sections for production of Pd; review of charged particle production routes

Production cross-sections of ¹⁰³Ag obtained by irradiating ^natPd and ^natCd with 70 MeV protons are presented and compared with ALICE-IPPE model calculations. Production of ¹⁰³Ag is of interest for the generation of ¹⁰³Pd widely used in brachytherapy. The investigated energy range of the ¹⁰³Rh(d,2n)¹⁰³Pd reaction was extended up to 40 MeV and the results were compared with the curves of ALICE-IPPE, EMPIRE-II and GNASH theoretical codes. Thick target yields were calculated. An overview and analysis of the most important charged particle induced production routes of ¹⁰³Pd is presented. An explanation of the apparent discrepancy in the activity measurements for ¹⁰³Rh based on X- or gamma-ray is given.     

In vivo and in vitro multitracer analyses of P-glycoprotein expression-related multidrug resistance

P-glycoprotein (Pgp) is an ABC (ATP binding cassette) transporter that is often overexpressed in tumours, contributing significantly to their multidrug resistance. In this study, we explored whether the radiotracers used in tumour diagnostics can be used for in vivo visualisation of Pgp-related multidrug resistance. We also examined the effects of different Pgp modulators on the accumulation of these radioligands in tumours with or without Pgp expression. In a SCID BC-17 mouse model, cells of the drug-sensitive KB-3-1 (MDR^–) and the KB-V1 Pgp-expressing (MDR⁺) human epidermoid carcinoma cell lines were inoculated to yield tumours in opposite flanks. For in vivo scintigraphic (biodistribution) and positron emission tomography (PET) examinations, the mice were injected with technetium-99m hexakis-2-methoxybutylisonitrile (^99mTc-MIBI), carbon-11 labelled methionine and fluorine-18 fluoro-2-deoxy-d-glucose (¹⁸FDG). For validation, in vitro cell studies with ^99mTc-MIBI, ^99mTc-tetrofosmin, [¹¹C]methionine and ¹⁸FDG were carried out using a gamma counter. The expression and function of the MDR product were proved by immunohistochemistry and spectrofluorimetry. ^99mTc-MIBI uptake was significantly lower in KB-V1 cells as compared with KB-3-1-derived tumours in vivo (Pgp⁺/Pgp^– =0.61±0.13; P<0.01) and cells in vitro (Pgp⁺/Pgp^– =0.08±0.01; P<0.001). Cyclosporin A reversed ^99mTc-MIBI uptake in the Pgp+ cells, while verapamil failed to modify it. ¹⁸FDG uptake was significantly higher in KB-V1 tumours (Pgp⁺/Pgp^– =1.36±0.05; P<0.01) and cells (Pgp⁺/Pgp^– =1.52±0.12; P<0.001). Whereas cyclosporin A eliminated the difference between FDG uptake in MDR⁺ and MDR^– cell lines, verapamil significantly increased it. When the animals were treated with verapamil, the ratio of ^99mTc-MIBI uptake in the MDR⁺ tumours to that in the MDR^– tumours decreased to 0.38±0.05 (P<0.01), while the ratio of ¹⁸FDG uptake increased to 2.1±0.3 (P<0.001). There were no significant differences in the [¹¹C]methionine uptake in the MDR⁺ and MDR^– tumours and cell lines, nor was [¹¹C]methionine accumulation modified by cyclosporin A. Parallel administration of ¹⁸FDG and ^99mTc-MIBI combined with verapamil treatment seems to be a good candidate as a non-invasive marker for the diagnosis of MDR-related Pgp expression in tumours.     

<Superscript>99m</Superscript>Tc-HYNIC octreotide in neuroblastoma

Disease status assessment of neuroblastoma patients requires computed tomography (or magnetic resonance imaging), bone scan, metaiodobenzylguanidine (MIBG) scan, bone marrow tests, and urine catecholamine measurements. There is no clinical experience concerning the evaluation of these patients by means of technetium-99m (^99mTc)-somatostatin analog scintigraphy. Furthermore, these radiopharmaceuticals are promising imaging agents owing to their lower cost, availability, dosimetry, and ease of preparation. An 8-year-old boy already diagnosed with stage-IV neuroblastoma received chemotherapy. In the follow-up, after obtaining the parents’ informed consent, iodin 131 (¹³¹I)-MIBG and ^99mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-octreotide scans were done on separate days to evaluate tumor extension. Even as the ¹³¹I-IBG scan showed mild diffuse uptake in the projection of both lung hili, the ^99mTc-HYNIC-octreotide scan showed multiple axial and appendicular bone uptakes and paravertebral, abdominal, mediastinal, and supraclavicular ganglionar uptakes. The ^99mTc-HYNIC-octreotide showed much more lesion extension than the ¹³¹I-MIBG. Therefore, ^99mTc-HYNIC-octreotide may be a promising radiopharmaceutical for the evaluation of neuroblastoma patients. This finding justifies the pre liminary evaluation of this tracer in the context of a clinical trial.     

RNA m6A甲基化修饰在肿瘤放疗和辐射损伤修复中的关键作用

N6-甲基腺苷(N6-methyladenosine, m6A)是真核信使RNA (mRNA)中最丰富的表观遗传学修饰。m6A甲基化修饰的发生由m6A甲基转移酶(Writers)催化;通过去甲基化酶(Erasers)去除;此外, m6A甲基化修饰被甲基化识别酶(Readers)识别。m6A甲基化修饰可调节RNA的剪接、翻译和稳定性。m6A甲基化修饰参与细胞活动中多种重要功能基因的生物学调控, 重要的是, m6A水平异常变化可影响肿瘤的发生、发展、转移以及复发等过程。电离辐射对m6A水平及m6A甲基化修饰相关酶的水平产生影响。在肿瘤放射治疗过程中, m6A修饰通过影响DNA损伤、肿瘤细胞辐射敏感性等, 进而影响放射治疗疗效。此外, 电离辐射影响m6A甲基化水平, 进而调控辐射损伤修复等过程。本文就RNA的m6A甲基化修饰在肿瘤放疗和辐射损伤修复中作用机制的研究进展进行综述, 旨在为临床肿瘤放射增敏剂及放射防护剂的研发提供新的思路。     

56Fe17+、12C6+重离子束照射后人淋巴细胞基因转录谱的改变

目的 探讨重离子束照射对人淋巴细胞基因转录谱的改变。方法 人淋巴细胞Peng-EBV分别经0.1、0.5和2 Gy ⁵⁶Fe¹⁷⁺、¹²C⁶⁺重离子束照射后,提取各实验组细胞总RNA,利用Agilent人表达谱基因芯片进行基因转录谱的检测并筛选差异表达基因;对差异表达基因进行GO分析;利用KEGG数据库对差异表达基因进行通路分析。结果 Peng-EBV细胞系经⁵⁶Fe¹⁷⁺、¹²C⁶⁺重离子束照射后,0.1、0.5和2.0 Gy剂量组共同差异表达基因分别为101、199和229个。3个剂量组共同差异表达基因14个,其中,GPSM1、TSPYL5、WFDC2、LAD1等基因在两种离子束各剂量组呈现特征性差异表达。0.1和0.5 Gy剂量组涉及主要基因功能包括细胞粘连、胞外基质构建等,参与的显著性Pathway通路分别为3和6条,主要为细胞因子受体相互作用通路等。2 Gy剂量组主要基因功能包括细胞黏连、Rho蛋白信号转导调节等,参与的显著性Pathway通路3条,主要为p53信号通路等。结论 ⁵⁶Fe¹⁷⁺、¹²C⁶⁺重离子束可诱导人淋巴细胞基因转录谱的改变,且不同剂量重离子可诱发不同的差异表达基因及通路。     

Rapid determination of Sr impurities in freshly “generator eluted” Y for radiopharmaceutical preparation

⁹⁰Y is one of the most useful radionuclides for radioimmunotherapeutic applications and has a half-life (t_1/2=64.14 h) suitable for most therapeutic applications, beta particles of high energy and decays to a stable daughter. It is significant that ⁹⁰Y is available conveniently and inexpensively from a radionuclide “generator” by decay of its parent, ⁹⁰Sr. Nevertheless, current and planned clinical applications with [⁹⁰Y] labelled compounds employ activity levels that cannot be readily obtained from an in-house generator, but from commercial sources. We have evaluated Eichrom's Sr-resin, either as an “in-house” generator or as a fast QC method for analysis of ⁹⁰Y solutions.In particular, for the development as a generator, we investigated the percentage of the radio-Sr in the first 8 M HNO₃ eluate: in this fraction the concentration of ⁹⁰Sr must be smaller than 10⁻⁵% (recommendations of the International Commission on Radiological Protection). For evaluation as a rapid QC method, we analyzed the concentration of ⁹⁰Y in all the fractions containing “only” radio-Sr: ⁹⁰Y should not be present in these eluates. After the collection of β⁻ and γ spectra and analysis of them, we concluded that commercial Sr-resin minicolumn cannot give us the results expected; we developed an in-house system loaded with 4 mL of Sr-resin which gave better results as a generator and a rapid QC method.     

Diagnostic Performance of 68Ga-DOTATATE PET/CT, 18F-FDG PET/CT and 131I-MIBG Scintigraphy in Mapping Metastatic Pheochromocytoma and Paraganglioma

Purpose

To evaluate the diagnostic performance of ⁶⁸Ga-DOTATATE ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT), ¹⁸F-FDG PET/CT and ¹³¹I-MIBG scintigraphy in the mapping of metastatic pheochromocytoma and paraganglioma.

Materials and Methods

Seventeen patients (male = 8, female = 9; age range, 13–68 years) with clinically proven or suspicious metastatic pheochromocytoma or paraganglioma were included in this prospective study. Twelve patients underwent all three modalities, whereas five patients underwent ⁶⁸Ga-DOTATATE and ¹³¹I-MIBG without ¹⁸F-FDG. A composite reference standard derived from anatomical and functional imaging findings, along with histopathological information, was used to validate the findings. Results were analysed on a per-patient and on per-lesion basis. Sensitivity and accuracy were assessed using McNemar’s test.

Results

On a per-patient basis, 14/17 patients were detected in ⁶⁸Ga-DOTATATE, 7/17 patients in ¹³¹I-MIBG, and 10/12 patients in ¹⁸F-FDG. The sensitivity and accuracy of ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG were (93.3 %, 94.1 %), (46.7 %, 52.9 %) and (90.9 %, 91.7 %) respectively. On a per-lesion basis, an overall of 472 positive lesions were detected; of which 432/472 were identified by ⁶⁸Ga-DOTATATE, 74/472 by ¹³¹I-MIBG, and 154/300 (patient, n = 12) by ¹⁸F-FDG. The sensitivity and accuracy of ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG were (91.5 %, 92.6 % p < 0.0001), (15.7 %, 26.0 % p < 0.0001) and (51.3 %, 57.8 % p < 0.0001) respectively. Discordant lesions were demonstrated on ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG.

Conclusions

Ga-DOTATATE PET/CT shows high diagnostic accuracy than ¹³¹I-MIBG scintigraphy and ¹⁸F-FDG PET/ CT in mapping metastatic pheochromocytoma and paraganglioma.     

Significance of alteration in biodistribution of labeled lymphocytes exposed to stannous ion

The biodistribution patterns of ^99mTc (^99mTc-lymph) and ¹¹¹In-lymphocytes with [¹¹¹In-(Sn)-lymph] or without (¹¹¹In-lymph) stannous ion treatment was compared in Lewis rats. Syngeneic lymphocytes were labeled with either 125 Ci (4.63 MBq) ^99mTc or 5 uCi (1985 kBq) ¹¹¹In per 2×10⁷ cells. Mean labeling efficiency for ^99mTc and ¹¹¹In was 68.61%±3.90% (SEM) and 87.22%±2.01% (SEM) respectively. ^99mTc-lymph (n=4), ¹¹¹In-lymph (n=6) and ¹¹¹In-(Sn)-lymph (n=6) rats received 2x10⁷ cells and were killed 18 h later. While ^99mTc-lymph demonstrated significantly less localization in spleen, lymph nodes, and blood (P(F)0.01) as compared with ¹¹¹In-lymph, ¹¹¹In-(Sn)lymph also demonstrated a significant difference (P[F]=0.0001) in lymph node accumulation when compared to ¹¹¹In-lymph. As the activity levels utilized are not associated with cell radiation damage, these alterations in biodistribution do not reflect viability or chromosomal damage, but appear related to stannous ion exposure.Support from the American Heart Association-Virginia Affiliate     

Transplant renography: 99m-Tc-DTPA versus 99m-Tc-MAG3. a preliminary note

^99mTc-MAG3 has been proposed as a replacement for both ¹³¹I-hippuran and ^99mTc-DTPA on clinical grounds. We undertook a prospective preliminary study to ascertain whether ^99mTc-MAG3 works better than ^99mTc-DTPA in the follow up of renal transplant recipients. Seventeen patients (21 renograms each MAG3 and DTPA) were studied, together, with a reference group of 10 patients in whom MAG3 and Hippuran clearance rates were determined simultaneously. As expected, ^99mTc-MAG3 analog images were excellent and ^99mTcMAG3 clearance correlated very well with ¹³¹I-hippuran clearance (r=0.978). MAG3 values were 60% of hippuran values. However, when the corresponding renographic and perfusion findings were faced with different diagnostic challenges, such as post transplant renal failure and rejection, ^99mTc MAG3 did not differ from ^99mTc-DTPA in a significant way. ^99mTc-DTPA was superior to ^99mtc-MAG3 in one case of rejection.     

Comparison of delayed hepatobiliary imaging using 99mTc-Sn-N-pyridoxyl-5-methyltryptophan and 67Ga-citrate imaging for diagnosis of hepatocellular carcinoma

Images were obtained both with a biliary agent, ^99mTc-Sn-N-pyridoxyl-5-methyltryptophan (^99mTc-PMT), and with ⁶⁷Ga-citrate in 40 cases of hepatocellular carcinoma and in 43 cases of other hepatic diseases and results were compared. Positive results were obtained by delayed ^99mTc-PMT imaging in 25 (63%) of 40 cases of hepatoma: the hepatic tumor showed increased uptake in 18 cases (45%) and equilibrated uptake in 7 cases (18%). Positive ⁶⁷Ga-citrate imaging was found in 28 (70%) of the 40 cases of hepatoma: increased uptake was seen in 24 cases (60%) and equilibrated uptake in 4 cases (10%). Of 15 cases of hepatoma giving negative results in the ^99mTc-PMT study, 7 cases (47%) took up ⁶⁷Ga-citrate, and 6 of these showed increased ⁶⁷Ga-citrate uptake by the hepatic tumors. A certain relation existed between the degree of histological differentiation of hepatomas and the intensity of ^99mTc-PMT uptake by those tumors, while such a histological correlation was denied for ⁶⁷Ga-citrate uptake by the tumors. Delayed ^99mTc-PMT imaging is preferable to ⁶⁷Ga-citrate imaging for increasing the specificity of diagnosis of hepatoma. ⁶⁷Ga-citrate should be used in those cases that do not give positive results with ^99mTc-PMT.     

Placenta,embryo, and tumor uptake of 67Ga-citrate and 59Fe-citrate

The uptake of gallium citrate Ga⁶⁷ and ferrous citrate Fe⁵⁹ was studied in pregnant rats with or without a 4-dimethylamino-stilben (DS)-induced sarcoma tumor. The liver and placenta of the mother concentrated ⁶⁷Ga, while the uptake of ⁶⁷Ga in the embryo was minimal. However, the embryo showed higher concentrations of ⁵⁹Fe. Preloading with iron did not affect the ⁶⁷Ga uptake of the placenta, but increased the uptake in the blood and liver of the mother. With regard to ⁵⁹Fe uptake, iron loading only affected the embryo liver. Tumors and the placenta showed a similar ⁶⁷Ga uptake but a different incorporation of ⁵⁹Fe. The probable mechanisms involved are discussed.     

Development of a modular system for the synthesis of PET [C]labelled radiopharmaceuticals

[¹¹C]labelled radiopharmaceuticals as N-[¹¹C]methyl-choline ([¹¹C]choline), l-(S-methyl-[¹¹C])methionine ([¹¹C]methionine) and [¹¹C]acetate have gained increasing importance in clinical PET and for the routine production of these radiopharmaceuticals, simple and reliable modules are needed to produce clinically relevant radioactivity. On the other hand, flexible devices are needed not only for the routine synthesis but also for more complex applications as the development of new tracers. The aim of this work was the adaptation of an Eckert Ziegler modular system for easy routine synthesis of [¹¹C]choline, [¹¹C]methionine and [¹¹C]acetate using components that account for straightforward scaling up and upgrades.     

Molecular structures involved in 67Ga and 59Fe binding by placenta and tumors

The binding of ⁶⁷Ga and ⁵⁹Fe by placenta and tumors was compared. After sonification, about 50% of the total radioactivity was present in the insoluble fraction consisting of heavy subcellular particles (mitochondria, fragments of membranes, nuclei, etc.) and known to be rich in lipo- and glycoproteins. Heat denaturation and gel filtration were used to study transferrin and ferritin distribution in the supernatant. The differences between ⁵⁹Fe and ⁶⁷Ga uptake in this supernatant seemed to indicate that the transferrin-ferritin system plays a less important role in ⁶⁷Ga binding than in ⁵⁹Fe binding.     

“Luxury perfusion” with99mTc-HMPAO and123I-IMP SPECT imaging during the subacute phase of stroke

To compare the merits of¹²³I-isopropyl-iodoam-phetamine (¹²³I-IMP) and^99mTc-HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with¹²³I-IMP and^99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal^99mTc-HMPAO SPECT and abnormal¹²³I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on^99mTc-HMPAO in areas corresponding to defects on the¹²³I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination,^99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on¹²³I-IMP. Crossed cerebellar diaschisis was found in 7 patients with^99mTc-HMPAO and was absent for both¹²³I-IMP and^99mTc-HMPAO in 3. We suggest that SPECT with⁹⁹mTc-HMPAO could show transient hyperemia not demonstrated by¹²³I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with^99mTc-HMPAO than with¹²³I-IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism.