Internal dosimetry of 64Cu-DOX-loaded microcapsules by Monte Carlo method.

Some of the issues regarding introducing new radiocompounds in nuclear medicine are the distribution patterns, delivered dose to different organs, diagnostic abilities and side effects. In this study, in order to assess the biodistribution of 64Cu-DOX-loaded microcapsules, rats were IV-injected with the microcapsules, and 1, 4, 14, and 24 h later, the activities of the targeted organs were measured (%ID/g). The accumulated activities were achieved by %ID/g curves, and S-factors were obtained by MCNP outputs. The MIRD formulation and Monte Carlo method were used to determine the absorbed dose in the target organs. The biodistribution data and PET-CT images showed that the lungs were where the majority of activity was seen. According to MIRD and MCNP, the maximum dose delivered in the lungs was 5.79E+01 mGy/MBq and 4.70E+01 mGy/MBq, respectively. Also, the effective dose was 1.2E+01 for MIRD and 8.31E+00 mSv/MBq for MCNP. These results indicate that 64Cu-DOX microcapsules can be considered a new radiocompound in pulmonary imaging, and MCNP simulation can be a reliable method for internal dosimetry.

Initial preclinical evaluation of 68 Ga-DOTA-(Ser) 3 -LTVSPWY peptide as a PET radiotracer for glioblastoma targeting and imaging.

PURPOSE: Imaging of glioblastoma multiform (GBM) tumor using 68 -Galium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaceticacid-Ser-Ser-Ser-Leu-Thr-Val-Ser-Pro-Trp-Tyr ( 68 Ga-DOTA-(Ser)3-LTVSPWY) as a PET radiotracer for HER2 receptor due to fact that this receptor plays a pivotal role in the tumorigenesis and tumor progression in a wide range of cancer. METHODS: 68 Ga-DOTA-(Ser) 3 -LTVSPWY was produced with high radiochemical purity. The affinity and specificity of this radiotracer toward HER2 receptor on the surface of glioma glioblastoma (U-87 MG) cell line were evaluated. Furthermore, the biodistribution and PET imaging of this radiolabeled peptide were investigated on xenografted U-87 MG tumor-bearing mice. RESULTS: The in-vitro specific binding study revealed that the 68 Ga-DOTA-(Ser) 3 -LTVSPWY binds to different cell lines with respect to their level of HER2 expression. The calculated K D and B max of radiolabeled peptide toward U-87 MG cell line were 5.5 ± 2.4 nmol/l and (2.4 ± 0.3) × 10 5 receptors per cell, respectively. The highest tumor uptake was observed at 30-min postinjection, whereas the tumor-to-muscle ratio was about four-fold. The acquired PET images distinctively show tumor site, which was blocked with excess nonlabeled peptide that revealed specific in-vivo targeting of 68 Ga-DOTA-(Ser) 3 -LTVSPWY for glioma. CONCLUSION: 68 Ga-DOTA-(Ser) 3 -LTVSPWY specifically recognizes HER2 receptors and could be a potential candidate for GBM imaging.

Synthesis and evaluation of 99mTc-DOTA-ARA-290 as potential SPECT tracer for targeting cardiac ischemic region.

Objectives: Myocardial infarction caused by ischemia of heart tissue is the main reason for death worldwide; therefore, early detection can reduce mortality and treatment costs. Erythropoietin (EPO) has protection effects on ischemic tissue due to nonhematopoietic peptide (pHBSP; ARA-290) which is derived from the B-subunit of EPO. Materials and Methods: We designed and synthesized a modified DOTA-(Lys-Dabcyl6, Phe7)-ARA-290 using Fmoc solid-phase peptide synthesis strategies. To improve serum stability, Fmoc-Lys-(Dabcyl)-OH as lipophilic amino acid was synthesized along with Fmoc-Phe-OH which then were substituted with Arg6 and Ala7, respectively; they were then investigated for the ability to detect ischemic cardiac imaging. DOTA-(Lys-Dabcyl6,Phe7)-ARA-290 was labeled with technetium 99m, and its radiochemical purity (RCP), stability in the presence of human serum and, specific bind to hypoxic H9c2 cells were evaluated. In vivo studies for biodistribution and SPECT scintigraphy were checked in a normal and cardiac ischemia rat model. Results: Radiolabeling purity was obtained more than 96% by ITLC, and in vitro stability of the radiopeptide up to 6 hr was 85%. The binding of 99mTc-ARA-290 to hypoxic cells was remarkably higher than normoxic cells (3 times higher than normoxic cells at 1 hr). Biodistribution and SPECT imaging on the cardiac ischemic model showed that radiopeptide considerably accumulated in the ischemic region (cardiac ischemic-to-lung rate = 3.65 ID/g % at 0.5 hr). Conclusion: The results of studies, in vitro and in vivo, indicated that 99mTc-DOTA-(Lys-Dabcyl6,Phe7)-ARA-290 could be an appropriate candidate for early diagnosis of cardiac ischemia.

pH-triggered intracellular release of doxorubicin by a poly(glycidyl methacrylate)-based double-shell magnetic nanocarrier.

Two core-double-shell pH-sensitive nanocarriers were fabricated using Fe3O4 as magnetic core, poly(glycidyl methacrylate-PEG) and salep dialdehyde as the first and the second shell, and doxorubicin as the hydrophobic anticancer drug. Two nanocarriers were different in the drug loading steps. The interaction between the first and the second shell assumed to be pH-sensitive via acetal cross linkages. The structure of nanocarriers, organic shell loading, magnetic responsibility, morphology, size, dispersibility, and drug loading content were investigated by IR, NMR, TG, VSM, XRD, DLS, HRTEM and UV-Vis analyses. The long-term drug release profiles of both nanocarriers showed that the drug loading before cross-linking between the first and second shell led to a more pH-sensitive nanocarrier exhibiting higher control on DOX release. Cellular toxicity assay (MTT) showed that DOX-free nanocarrier is biocompatible having cell viability greater than 80% for HEK-293 and MCF-7 cell lines. Besides, high cytotoxic effect observed for drug-loaded nanocarrier on MCF-7 cancer cells. Cellular uptake analysis showed that the nanocarrier is able to transport DOX into the cytoplasm and perinuclear regions of MCF-7 cells. In vitro hemolysis and coagulation assays demonstrated high blood compatibility of nanocarrier. The results also suggested that low concentration of nanocarrier have a great potential as a contrast agent in magnetic resonance imaging (MRI).

Targeting and imaging of HER2 overexpression tumor with a new peptide-based 68Ga-PET radiotracer.

Human epidermal growth factor receptor 2 (HER2) overexpression, as a predictive biomarker, is associated with more tumor aggressiveness and worse clinical outcomes in cancer, whereas it's accurate identification has led to the choice of effective treatments in many patients. In this study, a peptide-based PET probe (68Ga-DOTA-(Ser)3-LTVSPWY) was developed for imaging HER2 expression in tumors. The DOTA-(Ser)3-LTVSPWY was labeled with 68Ga and then was evaluated in vitro with HER2-positive SKOV-3 cell line; moreover, the in vivo biodistribution and PET/CT imaging were performed in xenografted tumor-bearing nude mice. The 68Ga-DOTA-(Ser)3-LTVSPWY displayed the high radiochemical purity greater than 95% and good stability in normal saline and human serum. The cellular binding experiments showed that the cell uptake in HER2-positive ovarian cancer cells could be effectively blocked by non-labeled peptide. The Kd and Bmax values for radiolabeled peptide were obtained at 2.5 ± 0.6 nM and (3.4 ± 0.2) × 105 sites per cell, respectively. Biodistribution study demonstrated that tumor-to-blood and tumor-to-muscle ratios were about 1.73 ± 0.36 and 3.78 ± 0.17 at 120 min after the injection of the radiolabeled peptide, respectively. Tumor imaging by PET/CT exhibited high contrast tumor image at 60 min after injection in animal models. Consequently, the results were indicative of the specific accumulation of 68Ga-DOTA-(Ser)3-LTVSPWY peptide in HER2-positive tumors and the suitability of its application as a PET probe for the diagnosis of HER2-overexpression tumor.

68Ga-DOTATATE PET/CT Compared with 131I-MIBG SPECT/CT in the Evaluation of Neural Crest Tumors.

OBJECTIVES: 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) has shown promising results in imaging of neural crest tumors (NCT). Herein, we compared the performance of 68Ga-DOTATATE PET/CT and 131I-MIBG single photon emission computed tomography (SPECT)/CT in the initial diagnosis, staging and follow-up of patients with NCTs. METHODS: Twenty-five patients (males:females=8:17; age range=2-71 years) with clinically proven or suspicious neuroblastoma, pheochromocytoma (PCC) or paraganglioma (PGL) were enrolled in this prospective study and underwent both 68Ga-DOTATATE PET/CT and 131I-MIBG SPECT/CT. A composite reference standard derived from histopathological information, together with anatomical and functional imaging findings, was used to validate the results. Imaging findings were assessed on a per-patient and on a per-lesion basis. Sensitivity and accuracy were assessed using McNemar's test. RESULTS: Referring to radiological imaging and histopathological findings as reference standard, 68Ga-DOTATATE and 131I-MIBG scans showed a sensitivity and accuracy of (100%, 96%) and (86.7%, 88%), respectively, on a per-patient basis. In PCC/PGL patients, on a per-patient basis, the sensitivity of 68Ga-DOTATATE was 100% and that of 131I-MIBG was 77.8%. In neuroblastoma patients, on a per-patient basis, the sensitivities of both 68Ga-DOTATATE and 131I-MIBG were 100%. Overall, in this patient cohort, 68Ga-DOTATATE PET/CT identified 52 lesions and 131I-MIBG SPECT/CT identified only 30 lesions. On a per-lesion analysis, 68Ga-DOTATATE was found to be superior to 131I-MIBG in detecting lesions in all anatomical locations, particularly osseous lesions. According to the McNemar test results, differences were not statistically significant. CONCLUSION: This relatively small patient cohort suggests 68Ga-DOTATATE PET/CT be superior to 131I-MIBG SPECT/CT in providing particularly valuable information for both primary staging and follow-up in patients with NCT.

Development of Ga-68 labeled, biotinylated thiosemicarbazone dextran-coated iron oxide nanoparticles as multimodal PET/MRI probe.

Bifunctional biotinylated thiosemicarbazone dextran-coated iron oxide Nanoparticles (NPs) were fabricated. Aldehyde groups of the oxidized dextran-coating layer were utilized to conjugate biotin as a tumor-targeting agent and thiosemicarbazide as a cation chelator on the surface of NPs. The final product was characterized for physicochemical and biological properties. It was compatible with red blood cells and did not change the blood coagulation time. It also showed a significantly enhanced affinity to biotin receptor-positive 4T1 cells compared to non-biotinylated ones. The r2 relaxivity coefficient value of the final product was 110.2 mM-1 s-1. Although biotinylated NPs were easily radiolabeled with Ga-68 at room temperature, the stable radiolabeled NPs were achieved at a higher temperature (60 °C). The radiolabeled NPs were majorly accumulated in the liver and spleen. However, about 5.4% ID/g of the radiolabeled NPs was accumulated within the 4T1 tumor site. Blocking studies was performed by the biotin molecules pre-injection showed uptake reduction in the 4T1 tumor (about 1.1% ID/g). The radiolabeled NPs could be used for the early detection of biotin receptor-positive tumors via PET-MRI.

Diagnostic fficiency of 68Ga-DOTATATE PET/CT as ompared to 99mTc-Octreotide SPECT/CT andonventional orphologic odalities in euroendocrine umors.

OBJECTIVES: In view of somatostatin receptor (SSR) expression on cell membranes of the majority of neuroendocrine tumors (NETs), functional imaging exploiting analogs of SSR alongside the anatomical imaging is the mainstay of this diagnostic modality. In this prospective study, we assessed and directly compared the diagnostic parameters of 68Ga-DOTATATE PET/CT and 99mTc-Octreotide SPECT/CT, as well as CT/MRI. METHODS: Twenty-five NET patients, either histologically proven or highly suspicious for NET, who were referred for Octreotide Scan were enrolled in this prospective study. They all underwent 99mTc-Octreotide SPECT/CT and then 68Ga-DOTATATE PET/CT. A blind interpretation was conducted for each imaging as well as for the previously obtained conventional imaging (CT or MRI). The patient-based and lesion-based analysis were conducted and the results of the three modalities were compared. The histopathologic confirmation or follow-up data were considered as the gold standard. Also, the impact of 68Ga-DOTATATE PET/CT on the patient's management was assessed. RESULTS: Overall, 77 lesions in 14 patients, 135 in 19 and 86 in 16 were detected on 99mTc-Octreotide SPECT/CT, 68Ga-DOTATATE PET/CT and CT/MRI, respectively. On patient-based analysis, the sensitivity was 65%, 90% and 71% for 99mTc-Octreotide SPECT/CT, 68Ga-DOTATATE PET/CT and CT/MRI, respectively. Also, the specificity was 80%, 80% and 75% for 99mTc-Octreotide SPECT/CT, 68Ga-DOTATATE PET/CT and CT/MRI, respectively. The correlation between 68Ga-DOTATATE PET/CT and 99mTc-Octreotide SPECT/CT results was significant (=0.02; kappa value=0.57), no correlation, however, was depicted with CI (=0.07; kappa value=0.35). On lesion-based analysis, 68Ga-DOTATATE PET/CT found more organs (=0.02) and lesions (=0.001) in comparison with 99mTc-Octreotide SPECT/CT and also more lesions in comparison with CT/MRI (=0.003). In addition, comparing with 99mTc-Octreotide SPECT/CT and CT/MRI, 68Ga-DOTATATE PET/CT revealed more data in 44% and 36% of the patients, resulting in management modification in 24% and 20%, respectively. CONCLUSION: Comparing with 99mTc-Octreotide SPECT/CT and CT/MRI, 68Ga-DOTATATE PET/CT provided more sensitivity and specificity in patients with NETs showing more involved organs as well as tumoral lesions. Also, 68Ga-DOTATATE PET/CT led to change of management in up to one-fourth of the patients, especially in a sub-group re-evaluated for recurrence.

68Ga-radiolabeled bombesin-conjugated to trimethyl chitosan-coated superparamagnetic nanoparticles for molecular imaging: preparation, characterization and biological evaluation.

INTRODUCTION: Nowadays, nanoparticles (NPs) have attracted much attention in biomedical imaging due to their unique magnetic and optical characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) are the prosperous group of NPs with the capability to apply as magnetic resonance imaging (MRI) contrast agents. Radiolabeling of targeted SPIONs with positron emitters can develop dual positron emission tomography (PET)/MRI agents to achieve better diagnosis of clinical conditions. METHODS: In this work, N,N,N-trimethyl chitosan (TMC)-coated magnetic nanoparticles (MNPs) conjugated to S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (DOTA) as a radioisotope chelator and bombesin (BN) as a targeting peptide (DOTA-BN-TMC-MNPs) were prepared and validated using fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), and powder X-ray diffraction (PXRD) tests. Final NPs were radiolabeled with gallium-68 (68Ga) and evaluated in vitro and in vivo as a potential PET/MRI probe for breast cancer (BC) detection. RESULTS: The DOTA-BN-TMC-MNPs with a particle size between 20 and 30 nm were efficiently labeled with 68Ga (radiochemical purity higher than 98% using thin layer chromatography (TLC)). The radiolabeled NPs showed insignificant toxicity (>74% cell viability) and high affinity (IC50=8.79 µg/mL) for the gastrin-releasing peptide (GRP)-avid BC T-47D cells using competitive binding assay against 99mTc-hydrazinonicotinamide (HYNIC)-gamma-aminobutyric acid (GABA)-BN (7-14). PET and MRI showed visible uptake of NPs by T-47D tumors in xenograft mouse models. CONCLUSION: 68Ga-DOTA-BN-TMC-MNPs could be a potential diagnostic probe to detect BC using PET/MRI technique.

Synthesis, characterization, and in vitro and in vivo 68Ga radiolabeling of thiosemicarbazone Schiff base derived from dialdehyde dextran as a promising blood pool imaging agent.

To be used as a carrier of 68Ga radioisotope for possible blood pool imaging studies, dialdehyde dextran thiosemicarbazone (DADTSC) Schiff base polymer with different thiosemicarbazone contents (TSCC) = 0.93, 2.43, and 3.4 mmol/g were synthesized and characterized by FT-IR, GPC, and CHNS. Although they were successfully radiolabeled at room temperature, stable radio-complexes were prepared at 60 °C. Effect of thiosemicarbazone content on the dissolution rate, cytotoxicity, coagulation and hemolysis activities, and radiolabeling efficiency of Schiff bases as well as on the in-vitro radio-complexes stability was investigated. DADTSC1 (TSCC = 0.93 mmol/g) showed a less cytotoxicity (cell viability, CV50 = 490 µg/ml), a better solubility, suitable coagulation and hemolytic activities, and a sufficient radiolabeling efficiency (Radiochemical purity (RCP) > 95%) and formed a stable (RCP > 90%) radio-complex, which be chosen for in-vivo biodistribution study in healthy rats through tissue sampling and counting for radioactivity. Like blood pool imaging agents, 68Ga-DADTSC1 presented a retention profile in blood circulation, though more studies, including imaging in larger mammals, are required.

Codelivery of Hydrophobic and Hydrophilic Drugs by Graphene-Decorated Magnetic Dendrimers.

In this study, a nanocarrier was prepared for the codelivery of a hydrophilic drug (doxorubicin) and a hydrophobic drug (curcumin) to cancer cells. In this nanocarrier, the edges of graphene oxide sheets were decorated with a magnetic-functionalized polyamidoamine dendrimer with hydrazone groups at the end of the polymer. The edge functionalization of graphene sheets not only improved the solubility and dispersibility of graphene sheets but also imparted the magnetic properties to the nanocarrier. The resulting nanocarrier was loaded with doxorubicin through the covalent linkage and curcumin through π-π stacking. The nanocarrier showed a pH-sensitive release for both drugs, and the drug release behavior was also improved by the coimmobilization of both drugs. The cytotoxicity assay of nanocarrier showed low toxicity toward MCF-7 cell compared to unmodified graphene oxide, which was attributed to the presence of a magnetic dendrimer. Besides, the drug-loaded nanocarrier was highly toxic for cells even more than for free drugs. The cellular uptake images revealed higher drug internalization for coloaded nanocarrier than for the nanocarrier loaded with one drug alone. All of the results showed that the codelivery of curcumin and doxorubicin in the presence of the nanocarrier was more effective in chemotherapy than the nanocarrier loaded with one drug.

Production of 68Ga-citrate Based on a SnO2 Generator for Short-Term Turpentine Oil-Induced Inflammation Imaging in Rats.

INTRODUCTION: Gallium-68 citrate has been successfully applied in the PET imaging of infections and inflammation in some centers; however further evaluation of the tracer in inflammation models is of great importance. METHODS: 68Ga-citrate prepared from [68Ga]GaCl3 (eluted form an SnO2 based 68Ge/68Ga generator) and sodium citrate at optimized conditions followed by quality control tests was injected to normal and turpentine-oil induced rats PET/CT imaging studies up to 290 min. RESULTS: 68Ga-citrate was prepared with acceptable radiochemical purity (>99 ITLC, >99% HPLC), specific activity (28-30 GBq/mM), chemical purity (Sn, Fe <0.3 ppm; Zn<0.2 ppm) in 15 min at 50°C. PET/CT imaging of the tracer demonstrated early detection of inflamed site in animal models in 60-80 min. CONCLUSION: This study demonstrated possible early detection of inflammation foci in vivo using 68Ga-citrate prepared using commercially available 68Ge/68Ga generators for PET imaging.

Preparation and radiolabeling of a lyophilized (kit) formulation of DOTA-rituximab with 9°Y and ¹¹¹In for domestic radioimmunotherapy and radioscintigraphy of non-Hodgkin's lymphoma.

BACKGROUND: On the basis of results of our previous investigations on 90Y-DTPA-rituximab and in order to fulfil national demands to radioimmunoconjugates for radioscintigraphy and radioimmunotherapy of Non-Hodgkin's Lymphoma (NHL), preparation and radiolabeling of a lyophilized formulation (kit) of DOTA-rituximab with 111In and 90Y was investigated. METHODS: 111In and 90Y with high radiochemical and radionuclide purity were prepared by 112Cd (p,2n)111In nuclear reaction and a locally developed 90Sr/90Y generator, respectively. DOTA-rituximab immunoconjugates were prepared by the reaction of solutions of p-SCN-Bz-DOTA and rituximab in carbonate buffer (pH = 9.5) and the number of DOTA per molecule of conjugates were determined by transchelation reaction between DOTA and arsenaso yttrium(III) complex. DOTA-rituximab immunoconjugates were labeled with 111In and 90Y and radioimmunoconjugates were checked for radiochemical purity by chromatography methods and for immunoreactivity by cell-binding assay using Raji cell line. The stability of radiolabeled conjugate with the approximate number of 7 DOTA molecules per one rituximab molecule which was prepared in moderate yield and showed moderate immunoreactivity, compared to two other prepared radioimmunoconjugates, was determined at different time intervals and against EDTA and human serum by chromatography methods and reducing SDS-polyacrylamide gel electrophoresis, respectively. The biodistribution of the selected radioimmunoconjugate in rats was determined by measurement of the radioactivity of different organs after sacrificing the animals by ether asphyxiation. RESULTS: The radioimmunoconjugate with approximate DOTA/rituximab molar ratio of 7 showed stability after 24 h at room temperature, after 96 h at 4°C, as the lyophilized formulation after six months storage and against EDTA and human serum. This radioimmunoconjugate had a biodistribution profile similar to that of 90Y-ibritumomab, which is approved by FDA for radioimmunotherapy of NHL, and showed low brain and lung uptakes and low yttrium deposition into bone. CONCLUSION: Findings of this study suggest that further investigations may result in a lyophilized (kit) formulation of DOTA-rituximab which could be easily radiolabeled with 90Y and 111In in order to be used for radioimmunotherapy and radioscintigraphy of B-cell lymphoma in Iran.

Preclinical studies of [61Cu]ATSM as a PET radiopharmaceutical for fibrosarcoma imaging.

[61Cu]diacetyl-bis(N4-methylthiosemicarbazone) ([61Cu] ATSM) was prepared using in house-made diacetyl-bis(N4-methylthiosemicarbazone) (ATSM) ligand and [61Cu]CuCl2 produced via the natZn(p, x)61Cu (180 muA proton irradiation, 22 MeV, 3.2 h) and purified by a ion chromatography method. [61Cu]ATSM radiochemical purity was >98 %, as shown by HPLC and RTLC methods. [61Cu]ATSM was administered into normal and tumor bearing rodents for up to 210 minutes, followed by biodistribution and co-incidence imaging studies. Significant tumor/non-tumor accumulation was observed either by animal sacrification or imaging. [61Cu]ATSM is a positron emission tomography (PET) radiotracer for tumor hypoxia imaging.

Preparation and evaluation of [(61)Cu]-thiophene-2-aldehyde thiosemicarbazone for PET studies.

BACKGROUND: [(61)Cu]Thiophene-2-aldehyde thiosemicarbazone ([(61)Cu]TATS) (4) was prepared according to an analogy of carrier copper compound with antitumor activity, for eventual use in PET. MATERIAL AND METHODS: [(61)Cu]TATS was prepared using copper-61 acetate and in-house made ligand (TATS) in one step. (61)Cu was produced via the (nat)Zn(p,x) (61)Cu nuclear reaction (180 mircoA, 22 MeV, 3.2 h) followed by a two-step chromatography method (222 GBq of (61)Cu(2+)). [(61)Cu]TATS preparation was optimized for reaction conditions (buffer concentration and temperature). The tracer was finally administered to normal rats for biodistribution studies. RESULTS: Total radiolabelling of the tracer took 30 minutes with a radiochemical purity of more than 90% (using HPLC and RTLC) and specific activity of about 250-300 Ci/mmol. The complex was stable in the presence of human serum for an hour. The biodistribution of copper cation and the tracer was checked in wild-type rats for up to 2 hours with significant spleen and lung uptake of the tracer. CONCLUSIONS: The production of (61)Cu via the (nat)Zn(p,x) (61)Cu is an efficient and reproducible method with high specific activity leading to the production and preliminary evaluation of [(61,)Cu]TATS, a potential PET tracer, was reported.

Evaluation of [67Ga]-insulin for insulin receptor imaging.

BACKGROUND: Radiolabelled human recombinant insulin can be used for the imaging of insulin receptors in some tumours where FDG has natural uptake and diminishes the value of its imaging. MATERIAL AND METHODS: Insulin was successively labelled with [(67)Ga]-gallium chloride after conjugation with freshly prepared cyclic DTPA-dianhydride (HPLC radiochemical purity assay > 96%) followed by biodistribution studies in normal rats, white blood cell labelling and preliminary SPECT studies. RESULTS: In vitro studies demonstrated the retention of radiolabelled insulin receptor affinity using freshly prepared human white blood cells at different blood sugar conditions. Preliminary in vivo studies in a normal rat model was performed to determine the biodistribution of the radioimmunoconjugate at up to 44 h. SPECT images revealed high uptake of the liver. CONCLUSION: Radiolabelled insulin is stable enough to be used in biological studies in order to image insulin receptors in diabetic conditions as well as possible tumour imaging applications. The data was consistent with other radiolabelled insulin studies.

Production and biological evaluation of [18F]-6-thia-14-fluoro-heptadecanoic acid.

BACKGROUND: [(18)F]-6-thia-14-fluoro-heptadecanoic acid 3b, a free fatty acid, has been used in myocardial PET imaging. In order to establish an automated synthesis module for routine production in the country, a study was performed for optimization of the production conditions as well as making modifications. MATERIAL AND METHODS: [(18)F]Benzyl-14-Fluoro-6-thia-heptadecanoate 2b was prepared in no-carrier-added (n.c.a) form from Benzyl-14-tosyloxy-6-thia-heptadecanoate 1 in one step at 90 degrees C in Kryptofix2.2.2/[(18)F] with acetonitrile as the solvent followed by Silica column chromatography. The radiolabelled ester 2 was then hydrolysed to yield [(18)F]-6-thia-14-fluoro-heptadecanoic 3b. The final solution was concentrated using the C(18) SPE system and administered to normal rats for biodistribution and co-incidence imaging studies. RESULTS: The synthesis took 15 min with overall radiochemical yield of 15-25% (EOS) and chemical-radiochemical purity of more than 90%. Automation was performed using a two-pot synthesis. The best imaging time was shown to be 140-180 minutes post injection. CONCLUSIONS: Using this procedure a fast, reliable, automated synthesis for the cardial PET tracer, i.e. [(18)F]FTHA, can be obtained without an HPLC purification step.