A simple and rapid technique for radiochemical separation of iodine radionuclides from irradiated tellurium using an activated charcoal column

A simple and inexpensive method for the separation of medically useful no-carrier-added (nca) iodine radionuclides from bulk amounts of irradiated tellurium dioxide (TeO₂) target was developed. The β⁻ emitting ¹³¹I radionuclide, produced by the decay of ¹³¹Te through the ^natTe(n, γ)¹³¹Te nuclear reaction, was used for standardization of the radiochemical separation procedure. The radiochemical separation was performed by precipitation followed by column (activated charcoal) chromatography. Quantitative post-irradiation recovery of the TeO₂ target material (98–99%), in a form suitable for reuse in future irradiations, was achieved. The overall radiochemical yield for the complete separation of ¹³¹I was 75–85% (n=8). The separated nca ¹³¹I was of high, 99%, radionuclidic and radiochemical purities and did not contain detectable amounts of the target material. This method can be adopted for the radiochemical separation of other different iodine radionuclides produced from tellurium matrices through cyclotron as well as reactor irradiation.     

Module-assisted preparation of Cu with high specific activity

In this work the production of ⁶⁴Cu via the ⁶⁴Ni(p,n)⁶⁴Cu reaction with optimized conditions for low current irradiation is presented. Different target setups and cleaning steps for lowering metal contaminations in the product were applied. ⁶⁴Cu with high specific activities up to 1685 GBq/μmol was produced despite low overall activity (∼4.2 GBq per run). The module processing leads to a highly reproducible, reliable product quality (<1 μg Cu and <7 μg Ni). Besides its diagnostic value ⁶⁴Cu may be of interest even for therapeutic purposes due to its decay characteristics.     

Development of a large scale production of Cu from Zn at the high energy proton accelerator: Closing the Zn cycle

A number of research irradiations of ⁶⁸Zn was carried out at Brookhaven Linac Isotope Producer aiming to develop a practical approach to produce the radioisotope ⁶⁷Cu through the high energy ⁶⁸Zn(p,2p)⁶⁷Cu reaction. Disks of enriched zinc were prepared by electrodeposition of ⁶⁸Zn on aluminum or titanium substrate and isolated in the aluminum capsule for irradition. Irradiations were carried out with 128, 105 and 92 MeV protons for at least 24 h. After irradiation the disk was chemically processed to measure production yield and specific activity of ⁶⁷Cu and to reclaim the target material. The recovered ⁶⁸Zn was irradiated and processed again. The chemical procedure comprised BioRad cation exchange, Chelex-100 and anion exchange columns. Reduction of the oxidation degree of copper allowed for more efficient Cu/Co/Zn separation on the anion exchange column. No radionuclides other than copper isotopes were detected in the final product. The chemical yield of ⁶⁷Cu reached 92-95% under remote handling conditions in a hot box. Production yield of ⁶⁷Cu averaged 29.2 μCi/[μA−h×g ⁶⁸Zn] (1.08 MBq/[μA−h×g ⁶⁸Zn]) in 24 h irradiations. The best specific activity achieved was 18.6 mCi/μg (688.2 MBq/μg).     

Production of no-carrier-added zirconium-89 for positron emission tomography

The production and radiochemical separation of ⁸⁹Zr from deuteron irradiation of natural yttrium targets is described. The production is optimized in order to minimize the level of the long lived ⁸⁸Zr. The yield of ⁸⁹Zr at 16 MeV incident deuteron energy is 18 ± 1.5 GBq/C (1.8 ± 0.15 mCi/μ Ah) for a target thickness of 240 mg/cm² and the contamination of ⁸⁸Zr is only 0.008% at EOB. The radiochemical separation of ⁸⁹Zr from the irradiated Y targets is by anion exchange chromatography with an overall yield of 80%. The intended use of ⁸⁹Zr is to label monoclonal antibodies (MoAbs) for tumour imaging using PET.     

Radiochemical studies relevant to 86Y production via 86Sr(p,n)86Y for PET imaging

A novel production technique of yttrium-86 based on bombardment of deposited strontium carbonate was investigated. ⁸⁶Y was produced via proton-induced reactions on SrCO₃ target that was prepared by the sedimentation method. Production yield of 0.37 mCi/μAh at 30 μA was measured by means of γ-ray spectrometry for natural target. The separation of ^86/87/88Y from Cu and Sr was carried out by two ion-exchange columns.     

Quantitative H and hyperpolarized He magnetic resonance imaging: Comparison in chronic obstructive pulmonary disease and healthy never-smokers

Objective

The aim of this study was to quantitatively evaluate the relationship between short echo time pulmonary ¹H magnetic resonance imaging (MRI) signal intensity (SI) and ³He MRI apparent diffusion coefficients (ADC), high-resolution computed tomography (CT) measurements of emphysema, and pulmonary function measurements.

Materials and methods

Nine healthy never-smokers and 11 COPD subjects underwent same-day plethysmography, spirometry, short echo time ((TE) = 1.2 ms) ¹H and diffusion-weighted hyperpolarized ³He MRI (b = 1.6 s/cm²) at 3.0 T. In addition, for COPD subjects only, CT densitometry was also performed.

Results

Mean ¹H SI was significantly greater for never-smokers (12.1 ± 1.1 arbitrary units (AU)) compared to COPD subjects (10.9 ± 1.3 AU, p = 0.04). The ¹H SI AP-gradient was also significantly greater for never-smokers (0.40 AU/cm, R² = 0.94) compared to COPD subjects (0.29 AU/cm, R² = 0.968, p = 0.05). There was a significant correlation between ¹H SI and ³He ADC (r = −0.58, p = 0.008) and significant correlations between ¹H MR SI and CT measurements of emphysema (RA₉₅₀, r = −0.69, p = 0.02 and HU₁₅, r = 0.66, p = 0.03).

Conclusions

The significant and moderately strong relationship between ¹H SI and ³He ADC, as well as between ¹H SI and CT measurements of emphysema suggests that these imaging methods and measurements may be quantifying similar tissue changes in COPD and that pulmonary ¹H SI may be used to monitor emphysema as a complement to CT and noble gas MRI.     

Chelating ion-exchange methods for the preparation of no-carrier-added Cu

IntroductionWe have developed a method for producing no-carrier-added ⁶⁴Cu by using chelating resin bearing iminodiacetic acid groups.MethodsWe optimized the conditions for the selective separation of radioactive Cu from Ni and Co using the chelating resin and produced no-carrier-added ⁶⁴Cu under the optimized conditions. We analyzed the amounts of the metal ions present in ⁶⁴Cu by inductively coupled-plasma mass spectroscopy (ICP-MS) and optical emission spectroscopy (ICP-OES), and performed radiolabeling of monoclonal antibodies in order to investigate the quality of the ⁶⁴Cu produced in this study.ResultsRadioactive Cu was separated from Ni and Co with 0.1 and 2 M HCl solutions. The yield of ⁶⁴Cu isolated from the ⁶⁴NiO target was almost 87%. The radiochemical purity of ⁶⁴Cu obtained from different amounts of ⁶⁴NiO targets was >99% in all cases. We found that the ⁶⁴Cu solution presented extremely low amounts of the metal ions and showed high specific activity (average: 595 GBq/μmol). Moreover, the antibodies were labeled with ⁶⁴Cu with a high average efficiency (average: 88%).ConclusionsWe could efficiently separate ⁶⁴Cu by using short ion-exchange columns. The chelating ion-exchange method provides a high quality of ⁶⁴Cu that is sufficient for the synthesis of ⁶⁴Cu-labeled antibodies and medical applications.     

Radiosynthesis of 1-[F]fluoroethyl-L-tryptophan as a novel potential amino acid PET tracer

¹⁸F labeled natural amino acids have been introduced as promising tumor imaging agents. A novel [¹⁸F]fluoro amino acid analog 1-[¹⁸F]fluoroethyl-L-tryptophan (1-[¹⁸F]FETrp) was designed and synthesized by a two-pot three-step procedure, including the synthesis of 1-[¹⁸F]fluoro-2- (tosyloxy)ethane, the [¹⁸F]fluoroethylation of the precursor N-Boc-L-tryptophan ethyl ester and following the deprotection of the tert-butoxycarbonyl and ethyl ester protecting groups. 1-[¹⁸F]FETrp was resulted in 0.9±0.2% (n=5) radiochemical yields (no decay corrected) by HPLC purification, within a total synthesis time of 65 min. The radiochemical purity of 1-[¹⁸F]FETrp was 95-97%. The radiosynthetic method needs to be further optimized to get a satisfying radiochemical yield.     

A high-yield and simplified procedure for the synthesis of α-[C]Methyl-l-tryptophan

Alpha-[¹¹C]methyl-l-tryptophan (AMT) has been synthesized by stereoselective methylation with [¹¹C]methyl iodide of the lithium-enolate generated by treating dimethyl 2(S),3a(R),8a(S)-(+)-hexahydro-8(phenylsulfonyl) pyrrolo[2,3-b]indole-1,2-dicarboxylate (2) with lithium diisopropyl amide (LDA) at −55 °C, followed by ring opening using trifluoroacetic acid and alkaline hydrolysis of the protecting groups. The crude product was purified by a simple reverse-phase C-18 Sep-Pak procedure. The purified product was isolated with an average radiochemical yield of 53 ± 12% (decay corrected) in 30–35 min from [¹¹C]methyl iodide. At end of synthesis (EOS), 138 ± 35 mCi (n = 24) of product was collected with a specific activity of ca. 1–1.3 Ci/μmol (EOS) (4–5 Ci/μmol @ EOB) starting from 1.5 Ci (EOB) of [¹¹C]CO₂.     

Excitation functions for deuteron induced reactions in natural nickel: Production of no-carrier-added 64Cu from enriched 64Ni targets for positron emission tomography

The excitation functions for the production of ⁶⁴Cu and other radionuclides by the deuteron irradiation of natural Ni targets have been measured up to 19 MeV incident energy. The excitation function for the ⁶⁴Ni(d, 2n)⁶⁴Cu reaction shows a maximum effective cross section of 7.2±0.9 mbarn at 16.2 MeV for the natural Ni target. Data have been used for the production of large quantities of ⁶⁴Cu by the deuteron irradiation of enriched (96.4%) ⁶⁴Ni targets. The radiochemical extraction procedures developed can produce either carrier-free ⁶⁴Cu or utilize a small amount (50 μg) of carrier. The thick target yield of ⁶⁴Cu is 107 ± 16 GBq/C (10.5 ± 1.6 mCi/μ Ah) and the contamination with ⁶¹Cu is only 0.29% at EOB. Data on the production yields of ⁶¹Cu, ⁶⁴Cu, ⁵⁷Ni, ⁵⁵Co, ⁵⁶Co ⁵⁷Co and ⁵⁸Co during the deuteron irradiation of natural Ni and enriched ⁶⁴Ni targets are presented.     

A method for the production of iron-52 with a very low iron-55 contamination

The production and radiochemical separation of ⁵²Fe from ⁴He irradiation of enriched ⁵⁰Cr target is described. Methods developed for the recovery of the target material (⁵⁰Cr) are also described. The yield of ⁵²Fe at 38 MeV incident ⁴He energy is 1667 ± 133 MBq/C (163 ± 13 μCi/μAh) at end of bombardment and the contamination of ⁵⁵Fe is only 0.008%.     

Carbon-11 labelled tyrosine to study tumor metabolism by positron emission tomography (PET)

To measure the rate of protein synthesis in human neoplasms by positron emission tomography, we prepared no carrier added DL-(1-¹¹C)-tyrosine by ¹¹C-carboxylation of the appropriate -lithioisocyanide followed by hydrolysis of the isocyanide function and removal of the protecting methoxy group. The purification, resolution and solvent switch to saline was performed by high performance liquid chromatography (HPLC). DL-(1-¹¹C)-Tyrosine in 0.1 N NaH₂PO₄ buffer was prepared with a radiochemical yield of 8%–16% (EOS, 35 min). The enantiomeric separation and solvent switch to saline were achieved in 5 min and 10 min respectively. Consequently L-(1-¹¹C)-tyrosine in physiological saline was obtained in 2%–4% radiochemical yield. Tumor accumulation in rats with the experimental WALKER 256 carcinosarcoma was observed for both the L- and D-isomer. Using positron emission tomography a tumor/muscle ratio of two was observed for the L-isomer 15 min after injection. The corresponding figure for the D-isomer was 2.5. The first clinical results with DL-(1-¹¹C)-tyrosine show accumulation of radioactivity in meningioma, a primary breast carcinoma and in liver metastases of a colonic carcinoma.     

Differentiation of intracranial tuberculomas and high grade gliomas using proton MR spectroscopy and diffusion MR imaging

Objective

The purpose of this study was to determine whether proton MR spectroscopy (¹H MRS) and diffusion-weighted (DW) imaging can be used to differentiate intracranial tuberculomas from high grade gliomas (HGGs).

Materials and methods

A total of 41 patients (19 with intracranial tuberculomas and 22 with HGGs) were examined in our study. ¹H MRS and DW imaging were performed at a 1.5T MR scanner before operation or treatment. Concentrations of N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lipid and lactate (LL) in the contrast-enhancing rim of each lesion were expressed as metabolite ratios and were normalized to the contralateral hemisphere. The apparent diffusion coefficient (ADC) was also calculated. The metabolite ratios and ADC values in the enhancing rim of intracranial tuberculomas and HGGs were compared using the Wilcoxon rank sum test. Diagnostic accuracy was compared using receiver operating characteristic (ROC) analysis.

Results

Significant differences were found in the maximum Cho/Cr (P = 0.015), Cho/NAA (P = 0.001) and Cho/Cho-n ratios (P = 0.002), and minimum ADC value (P < 0.001) between the intracranial tuberculomas and HGGs. Diagnostic accuracy was higher by minimum ADC value than maximum Cho/Cr, Cho/NAA and Cho/Cho-n ratios (93.8% versus 75.7%, 80.8% and 78.1%).

Conclusion

These results suggest a promising role for ¹H MRS and DW imaging in the differentiation between the intracranial tuberculomas and HGGs.     

Value of F-FDG PET/CT in the diagnosis of primary gastric cancer via stomach distension

Objective

To clarify the usefulness of ¹⁸F-FDG PET/CT for detecting primary gastric cancer via gastric distention using a mixture of milk and Diatrizoate Meglumine.

Materials and methods

A total of 68 patients (male: 47, female: 21; age: 41–87 years) suspected of gastric carcinoma underwent ¹⁸F-FDG PET/CT imaging. After whole-body PET/CT imaging in a fasting state, the patients drank a measured amount of milk with Diatrizoate Meglumine. Local gastric district PET/CT imaging was performed 30 min later. The imaging was analyzed by semi-quantitative analysis, standardized uptake value (SUV) of the primary tumor was measured in a region of interest. The diagnosis results were confirmed by gastroscopy, pathology, and follow-up results.

Results

Of the 68 patients, 56 malignant gastric neoplasm patients (male: 37, female: 19) were conformed. The sensitivity, specificity, positive predictive value and negative predictive value of fasting whole-body PET/CT imaging for a primary malignant tumor were 92.9%, 75.0%, 94.5%, and 69.0%, respectively. The values for distension with a mixture of milk and Diatrizoate Meglumine were 91.1%, 91.7%, 98.1%, and 68.8%, respectively. The area under the curve was 0.919 ± 0.033 and 0.883 ± 0.066 for the diagnosis of gastric cancer with SUV_max in a fasting state and after intake of mixture respectively, the differences were not statistically significant (P = 0.359). Using gastric distension with a mixture of milk and Diatrizoate Meglumine, the mean ratio of the lesion's SUV_max to the adjacent gastric wall SUV_max increased significantly from 3.30 ± 3.05 to 13.50 ± 15.05, which was statistically significant (P < 0.001).

Conclusions

¹⁸F-FDG PET/CT imaging is highly accurate for the diagnosis of primary gastric carcinoma. Gastric distention can display the lesions more clearly, however, it cannot significantly improve diagnostic accuracy.     

Clinical values for abnormal F-FDG uptake in the head and neck region of patients with head and neck squamous cell carcinoma

Purpose

Fluorine 18-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) is used to identify index or second primary cancer (SP) of the head and neck (HN) through changes in ¹⁸F-FDG uptake. However, both physiologic and abnormal lesions increase ¹⁸F-FDG uptake. Therefore, we evaluated ¹⁸F-FDG uptake in the HN region to determine clinical values of abnormal tracer uptake.

Methods

A prospective study approved by the institutional review board was conducted in 314 patients with newly diagnosed HN squamous cell carcinoma (HNSCC) and informed consent was obtained from all enrolled patients. The patients received initial staging workups including ¹⁸F-FDG PET/CT and biopsies. All lesions with abnormal HN ¹⁸F-FDG uptake were recorded and most of those were confirmed by biopsies. Diagnostic values for abnormal ¹⁸F-FDG uptake were calculated.

Results

Abnormal ¹⁸F-FDG uptake was identified in primary tumors from 285 (91.9%) patients. False-negative results were obtained for 22.3% (23/103) T1 tumors and 2.2% (2/93) T2 tumors (P < 0.001). Thirty-eight regions of abnormal ¹⁸F-FDG uptake were identified in 36 (11.5%) patients: the thyroid (n = 13), maxillary sinus (n = 7), palatine tonsil (n = 6), nasopharynx (n = 5), parotid gland (n = 2) and others (n = 5). Synchronous SP of the HN was identified in eight (2.5%) patients: the thyroid (n = 5), palatine tonsil (n = 2), and epiglottis (n = 1). The sensitivity and specificity of ¹⁸F-FDG PET/CT for identification of SPs were 75.0% and 98.7%, respectively.

Conclusions

¹⁸F-FDG PET/CT is a reliable method for tumor staging and identify SP in HN region, promoting appropriate therapeutic planning. Additional examinations may be required to identify superficial or small-volume tumors.     

Recovery of 131I from alkaline solution of n-irradiated tellurium target using a tiny Dowex-1 column

A simple and inexpensive ion-exchange chromatography method for the separation of medically useful no-carrier-added (nca) iodine radionuclides from bulk amounts of irradiated tellurium dioxide (TeO₂) target was developed and tested using ¹³¹I. The radiochemical separation was performed using a very small Dowex-1×8 ion-exchange column. The overall radiochemical yield for the complete separation of ¹³¹I was 92±1.8 (standard deviation) % (n=8). The separated nca ¹³¹I was of high, ～99%, radionuclidic and radiochemical purity and did not contain detectable amounts of the target material. This method may be adopted for the radiochemical separation of other different iodine radionuclides produced from tellurium matrices through cyclotron as well as reactor irradiation.     

Evaluation of F-FDG and F-FLT for monitoring therapeutic responses of colorectal cancer cells to radiotherapy

In order to compare the efficacy of ¹⁸F-fluorothymidine (FLT) and ¹⁸F-fluorodeoxyglucose (FDG) for monitoring early responses to irradiation, two human colorectal cancer (CRC) cell lines SW480 and SW620, which were derived from the primary lesions and the metastatic lymph node, underwent X-ray irradiation of 0, 10, or 20 Gy and were examined at 0, 24 and 72 h After irradiation, reduced proliferation of both SW480 and SW620 cells was observed in a dose-dependent manner (P < 0.001), G0-G1 arrest was also noted in both cell types after 72 h in the 20 Gy group (P < 0.001). Although increased apoptosis was observed in both cell lines after irradiation (P < 0.001), a greater percentage of SW480 cells underwent apoptosis in response to irradiation than SW620 cells. Increased Hsp27 and decreased integrin β₃, Ki67 and VEGFR2 expression was observed over time via immunocytochemistry and Western blot analysis (P < 0.001), however, no significant changes were noted in response to irradiation. Finally, reduced uptake of ¹⁸F-FLT by SW480 or SW620 cells was observed at 24-h post-irradiation, however, reduced ¹⁸F-FDG uptake was only observed after 72 h. Therefore, we conclude that ¹⁸F-FLT is a more suitable positron emission tomography (PET) tracer for monitoring early responses to irradiation in primary and metastatic lymph node CRC cells.     

Evaluation of uncertainty and detection limits in Pb and Po measurement in water by alpha spectrometry using Po spontaneous deposition onto a silver disk

An easy and accurate method for the determination of ²¹⁰Pb and ²¹⁰Po in water using ²¹⁰Po spontaneous deposition onto a silver disk is proposed and assessed for its detection capabilities according to the ISO Guide for the expression of uncertainty in measurement (GUM) and ISO Standard 11929-7 concerning the evaluation of the characteristic limits for ionizing radiation measurements. The method makes no assumption on the initial values of the activity concentrations of ²¹⁰Pb, ²¹⁰Bi and ²¹⁰Po in the sample to be analyzed, and is based on the alpha spectrometric measurement of ²¹⁰Po in two different aliquots: the first one measured five weeks after the sampling date to ensure radioactive equilibrium between ²¹⁰Pb and ²¹⁰Bi and the second after a sufficient time for the ingrowth of ²¹⁰Po from ²¹⁰Pb to be significant. As shown, for a recommended time interval of seven months between ²¹⁰Po measurements, the applicability of the proposed method is limited to water samples with a ²²⁶Ra to ²¹⁰Pb activity ratio C_Ra/C_Pb≤4, as usual in natural waters. Using sample and background counting times of 24 h and 240 h, respectively, the detection limit of the activity concentration of each radionuclide at the sampling time for a 1 L sample typically varies between 0.7 and 16 mBq L⁻¹ for ²¹⁰Pb in water samples with an initial activity of ²¹⁰Po in the range 0-200 mBq L⁻¹, and between 0.6 and 8.5 mBq L⁻¹ for ²¹⁰Po in water samples with an initial activity of ²¹⁰Pb in the same range.     

Chemical processing for production of no-carrier-added selenium-73 from germanium and arsenic targets and synthesis of l-2-amino-4-([73Se]methylseleno) butyric acid (l-[73Se]selenomethionine)

The Ge(⁴He, xn) and ⁷⁵As(p, 3n) reactions were compared as the best potential routes for routine production of selenium-73 (⁷³Se) for medical applications. With 26 MeV α particles, available with compact cyclotrons, the first reaction required an enriched ⁷⁰Ge target of sodium metagermanate to give a production yield of 1 mCi/μAh (0.037 GBq/μAh) in a 105 mg/cm² target. With 55 MeV protons the As(p, 3n) reaction on natural arsenic yielded 20 mCi/μAh (0.74 GBq/μAh) in a 685 mg/cm² target. A simple method was developed and optimized for both targets in order to isolate and purify the no-carrier-added selenium in the elemental form with a radiochemical yield greater than 75% in less than 90 min. An automated radiochemical processing unit has been designed for the routine production of 100–150 mCi (3.7–5.5 GBq) batches of carrier-free ⁷³Se ready for radiopharmaceutical labeling. 30 mCi (1.11 GBq) (EOS) of l-2-amino-4-([⁷³Se]methylseleno) butyric acid (l-[⁷³Se]selenomethionine) ready for injection with a specific activity of 5 Ci/mmol (185 GBq/mmol) (EOS) were obtained through a fast chemical synthesis. Radiation absorbed dose estimates for l-[⁷³Se]selenomethionine have been determined. A value of 0.70 rem/mCi (0.19 mSv/MBq) administered was calculated for the risk from irradiation in man. The first human PET investigation with [⁷³Se]selenomethionine showed a very good delineation between liver and pancreas.