Cellular lethal damage of 64Cu incorporated in mammalian genome evaluated with Monte Carlo methods.

Purpose: Targeted Radionuclide Therapy (TRT) with Auger Emitters (AE) is a technique that allows targeting specific sites on tumor cells using radionuclides. The toxicity of AE is critically dependent on its proximity to the DNA. The aim of this study is to quantify the DNA damage and radiotherapeutic potential of the promising AE radionuclide copper-64 (64Cu) incorporated into the DNA of mammalian cells using Monte Carlo track-structure simulations. Methods: A mammalian cell nucleus model with a diameter of 9.3 µm available in TOPAS-nBio was used. The cellular nucleus consisted of double-helix DNA geometrical model of 2.3 nm diameter surrounded by a hydration shell with a thickness of 0.16 nm, organized in 46 chromosomes giving a total of 6.08 giga base-pairs (DNA density of 14.4 Mbp/µm3). The cellular nucleus was irradiated with monoenergetic electrons and radiation emissions from several radionuclides including 111In, 125I, 123I, and 99mTc in addition to 64Cu. For monoenergetic electrons, isotropic point sources randomly distributed within the nucleus were modeled. The radionuclides were incorporated in randomly chosen DNA base pairs at two positions near to the central axis of the double-helix DNA model at (1) 0.25 nm off the central axis and (2) at the periphery of the DNA (1.15 nm off the central axis). For all the radionuclides except for 99mTc, the complete physical decay process was explicitly simulated. For 99mTc only total electron spectrum from published data was used. The DNA Double Strand Breaks (DSB) yield per decay from direct and indirect actions were quantified. Results obtained for monoenergetic electrons and radionuclides 111In, 125I, 123I, and 99mTc were compared with measured and calculated data from the literature for verification purposes. The DSB yields per decay incorporated in DNA for 64Cu are first reported in this work. The therapeutic effect of 64Cu (activity that led 37% cell survival after two cell divisions) was determined in terms of the number of atoms incorporated into the nucleus that would lead to the same DSBs that 100 decays of 125I. Simulations were run until a 2% statistical uncertainty (1 standard deviation) was achieved. Results: The behavior of DSBs as a function of the energy for monoenergetic electrons was consistent with published data, the DSBs increased with the energy until it reached a maximum value near 500 eV followed by a continuous decrement. For 64Cu, when incorporated in the genome at evaluated positions (1) and (2), the DSB were 0.171 ± 0.003 and 0.190 ± 0.003 DSB/decay, respectively. The number of initial atoms incorporated into the genome (per cell) for 64Cu that would cause a therapeutic effect was estimated as 3,107 ± 28, that corresponds to an initial activity of 47.1 ± 0.4 × 10-3 Bq. Conclusion: Our results showed that TRT with 64Cu has comparable therapeutic effects in cells as that of TRT with radionuclides currently used in clinical practice.

In silico Study on the Binding Interactions of SSTA and 18F-SSTA Towards Somatostatin Receptor Subtype 2.

BACKGROUND: Somatostatin analogs (SSTAs) are versatile drugs that target a group of proteins known as somatostatin receptors. SSTAs are used for the treatment and PET-molecular imaging of Neuro Endocrine Tumors (NET), for they are labeled with the radionuclide 18F, a positron emitter radionuclide. OBJECTIVE: The aim of this work was to theoretically study the binding interactions of SSTA labeled with 18F (half-life of 109.7 min) and somatostatin receptor subtype 2. As the labeling of SSTA with 18F required the use of a prosthetic group, a hydrophilicity enhancer, and a linker, the influence of these traits on the interactions of 18F-SSTA with the SSTR-2 binding site was studied. METHODS: The binding modes of 18F-labeled analogues with SSTR-2 were studied by using protein homology modelling, non-equilibrium molecular dynamics, and molecular docking calculations, by means of three docking software: MVD, MOE, and VINA. RESULTS: The results showed the main role of Asp122, Asn276, Phe272 and Phe294 from the SSTR-2 binding site, which form interactions with residues Lys, Trp, Tyr, and Thr from 18F-labeled somatostatin analogues. CONCLUSION: The interaction between Lys (from 18F-SSTA) and Asp122 (from SSTR-2) was identified as the most energetic and considered the one that drives the binding between 18F-SSTA and SSTR-2 (the anchor interaction). Despite the presence of prosthetic groups, linkers, and hydrophilicity enhancers, all the studied 18F-SSTA formed the anchor interaction. The trend in the results agreed with the experimental reports, identifying the main role of Asp122 in the binding of somatostatin-14 to SSTR-2.

Current status on cyclotron facilities and related infrastructure supporting PET applications in Latin America and the Caribbean.

This review presents the results of a survey conducted by the International Atomic Energy Agency on cyclotrons and related infrastructure used for radionuclide and radiopharmaceutical production which are supporting PET imaging applications in Latin America and the Caribbean region.

Comparative analysis of striatal [18 F]FDOPA uptake in a partial lesion model of Parkinson's disease in rats: Ratio method versus graphical model.

Animal models of Parkinson's disease are useful to evaluate new treatments and to elucidate the etiology of the disease. Hence, it is necessary to have methods that allow quantification of their effectiveness. [18 F]FDOPA-PET (FDOPA-PET) imaging is outstanding for this purpose because of its capacity to measure changes in the dopaminergic pathway noninvasively and in vivo. Nevertheless, PET acquisition and quantification is time-consuming making it necessary to find faster ways to quantify FDOPA-PET data. This study evaluated Male Wistar rats by FDOPA, before and after being partially injured with 6-OHDA unilaterally. MicroPET scans with a duration of 120 min were acquired and Patlak reference plots were created to estimate the influx constant Kc in the striatum using the full dynamic scan data. Additionally, simple striatal-to-cerebral ratios (SCR) of short static acquisitions were computed and compared with the Kc values. Good correlation (r > 0.70) was obtained between Kc and SCR, acquired between 80-120 min after FDOPA administration with frames of 10 or 20 min and both methods were able to separate the FDOPA-uptake of healthy controls from that of the PD model (SCR -28%, Kc -71%). The present study concludes that Kc and SCR can be trustfully used to discriminate partially lesioned rats from healthy controls.

Semiautomatic assessment of whole-body tumor burden with 18F-PSMA-1007 in biochemical recurrent prostate cancer.

OBJECTIVE: The aim of the study was to evaluate the 18F-PSMA-1007 PET/computed tomography (CT) semiautomatic volumetric parameters to assess the whole-body tumor burden and its correlation with prostate-specific antigen (PSA) and Gleason score in patients with biochemically recurrent prostate cancer (PCa). MATERIALS AND METHODS: A total of 110 patients referred for 18F-PSMA-1007 PET/CT due to biochemical recurrence were retrospectively analyzed. Whole-body total lesion prostate-specific membrane antigen (wbTl-PSMA) and whole-body PSMA-derived tumor volume (wbPSMA-TV) metrics on 18F-PSMA-1007 were obtained semiautomatically in dedicated software. A Spearman test was performed to explore the correlation of volumetric imaging parameters with PSA levels and Gleason score. To analyze the association between volumetric measures and PSA subgroups, we used a Kruskal-Wallis test and a Dunn's test to identify each group causing an observed difference. RESULTS: A total of 492 metastatic lesions were analyzed, and a significant correlation was found between wbTL-PSMA (R = 0.63, P < 0.0001) and wbPSMA-TV (R = 0.49, P < 0.0001) with serum PSA. A statistically significant difference with wbTL-PSMA was found in patients with a PSA less than or equal 0.5 ng/ml and PSA in the range of 0.51-1.0 ng/ml. CONCLUSION: 18F-PSMA-1007 PSMA volumetric parameters can provide a quantitative imaging biomarker for whole-body tumor burden.

[68Ga]Ga-iPSMA-Lys3-Bombesin: Biokinetics, dosimetry and first patient PET/CT imaging.

BACKGROUND: The prostate-specific membrane antigen (PSMA) and the gastrin-releasing peptide receptor (GRPR) are overexpressed in prostate cancer (PCa). In preclinical studies, the iPSMA-Lys3-Bombesin (iPSMA-BN) heterodimeric ligand has shown a suitable affinity for PSMA and GRPR. This research aimed to assess the biokinetics and radiation dosimetry of [68Ga]Ga-iPSMA-BN in four healthy volunteers based on biodistribution data obtained from whole-body PET/CT studies, as well as to visualize the [68Ga]Ga-iPSMA-BN tumor uptake in a patient with PCa. METHODS: PET/CT images acquired at 5 min, 0.5, 1, and 2 h after radiotracer administration (124.5 ± 2.1 MBq) were corrected for attenuation, scattering, dead-time, and decay. The activity in the segmented volumes of interest (VOIs) in each source organ at different times was adjusted to mono- and bi-exponential biokinetic models (A(t)VOI), from which the total disintegrations (N) were calculated to assess the internal radiation doses by using the OLINDA V1.1 code. RESULTS: Images from the patient showed an evident uptake by the metastasis (SUVmax of 4.7) and by the organs expressing GRPR (pancreas) and PSMA (salivary glands). The average effective dose was 2.70 ± 0.05 mSv, which was like those known for most of the 68Ga studies, making [68Ga]Ga-iPSMA-BN a promising dual-target PET imaging radiotracer for PCa. CONCLUSIONS: [68Ga]Ga-iPSMA-BN, capable of detecting both PSMA and GRPR with suitable biokinetics and dosimetric patterns, could be a potential complementary diagnostic tool for the improvement of prostate cancer PET imaging.

Production of Copper Radionuclides in Compact Medical Cyclotrons using Solid Targets.

Over the last several years there has been a growing interest in the use of radiopharmaceuticals labeled with metallic radionuclides, especially isotopes of copper (Cu). Cu has a unique set of radionuclides with a potential application not only for diagnostic imaging but also for applications in targeted radionuclide therapy. To review the methods and routes used for the production of Cu radionuclides in compact medical cyclotrons (Ep<20 MeV) using solid targets. The cyclotron production of Cu radionuclides using solid targets has proven to be very efficient. The large number of compact medical cyclotrons distributed worldwide, and the high target yields in the production of Cu radionuclides achieved at these energies, form a potential network of distribution to satisfy the growing demand for these radionuclides, especially 64Cu.

IAEA contribution to the development of 64Cu radiopharmaceuticals for theranostic applications.

Copper-64 is a very attractive radioisotope with unique nuclear properties that allow using it as both a diagnostic and therapeutic agent, thus providing an almost ideal example of a theranostic radionuclide. A characteristic of Cu-64 stems from the intrinsic biological nature of copper ions that play a fundamental role in a large number of cellular processes. Cu-64 is a radionuclide that reflects the natural biochemical pathways of Cu-64 ions, therefore, can be exploited for the detection and therapy of certain malignancies and metabolic diseases. Beside these applications of Cu-64 ions, this radionuclide can be also used for radiolabelling bifunctional chelators carrying a variety of pharmacophores for targeting different biological substrates. These include peptide-based substrates and immunoconjugates as well as small-molecule bioactive moieties. Fueled by the growing interest of Member States (MS) belonging to the International Atomic Energy Agency (IAEA) community, a dedicated Coordinated Research Project (CRP) was initiated in 2016, which recruited thirteen participating MS from four continents. Research activities and collaborations between the participating countries allowed for collection of an impressive series of results, particularly on the production, preclinical evaluation and, in a few cases, clinical evaluation of various 64Cu-radiopharmaceuticals that may have potential impact on future development of the field. Since this CRP was finalized at the beginning of 2020, this short review summarizes outcomes, outputs and results of this project with the purpose to propagate to other MS and to the whole scientific community, some of the most recent achievements on this novel class of theranostic 64Cu-pharmaceuticals.

Quantitative Analysis of [18F]FFMZ and [18F]FDG PET Studies in the Localization of Seizure Onset Zone in Drug-Resistant Temporal Lobe Epilepsy.

BACKGROUND: Positron emission tomography (PET) imaging in epilepsy is an in vivo technique that allows the localization of a possible seizure onset zone (SOZ) during the interictal period. Stereo-electro-encephalography (SEEG) is the gold standard to define the SOZ. The objective of this research was to evaluate the accuracy of PET imaging in localizing the site of SOZ compared with SEEG. METHODS: Seven patients with refractory temporal lobe epilepsy (Ep) and 2 healthy controls (HC) underwent 2 PET scans, one with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and another with 2'-[18F]fluoroflumazenil (FFMZ), acquired 1 day apart. FDG was acquired for 10 min (static scan) 1 h after administration. An FFMZ scan was acquired for 60 min from radiopharmaceutical administration in a dynamic mode. Each brain PET image was segmented using a standard template implemented in PMOD 3.8. The pons was used as the reference region for modeling of the nondisplaceable binding potential (BPND)for FFMZ, and to obtain uptake ratios for FDG. SEEG studies of patients were performed as a part of their surgical evaluation to define the SOZ. RESULTS: Well-defined differences between HC and Ep were found with both radiopharmaceuticals, showing the utility to identify abnormal brain regions using quantitative PET imaging. Lateralization of the SOZ findings by PET (lower uptake/binding in a specific brain hemisphere) matched in 86% for FFMZ and 71% for FDG with SEEG data. CONCLUSION: Quantitative PET imaging is an excellent complementary tool that matches reasonably well with SEEG to define SOZ in presurgical evaluation.

Porphyrins as ligands for 64copper: background and trends.

Porphyrins and 64Cu have emerged as a novel synergic option for applications in PET molecular imaging. Both the characteristics and photophysical properties of macrocyclic porphyrins and the relatively long half-life of the copper isotope, in addition to the increased tumor-specific uptake of porphyrins compared to normal cells, make this complex an attractive option not only for diagnosis but also for therapeutic applications. Herein, we present an overview of the latest results on the development of PET agents based on porphyrins and 64Cu, including methods used to improve the selectivity of these macrocycles when conjugated with biological units such as monoclonal antibodies, peptides or proteins.

Disruption of behavior and brain metabolism in artificially reared rats.

Early adverse life stress has been associated to behavioral disorders that can manifest as inappropriate or aggressive responses to social challenges. In this study, we analyzed the effects of artificial rearing on the open field and burial behavioral tests and on GFAP, c-Fos immunoreactivity, and glucose metabolism measured in anxiety-related brain areas. Artificial rearing of male rats was performed by supplying artificial milk through a cheek cannula and tactile stimulation, mimicking the mother's licking to rat pups from the fourth postnatal day until weaning. Tactile stimulation was applied twice a day, at morning and at night, by means of a camel brush on the rat anogenital area. As compared to mother reared rats, greater aggressiveness, and boldness, stereotyped behavior (burial conduct) was observed in artificially reared rats which occurred in parallel to a reduction of GFAP immunoreactivity in somatosensory cortex, c-Fos immunoreactivity at the amygdala and primary somatosensory cortex, and lower metabolism in amygdala (as measured by 2-deoxi-2-[18 fluoro]-d-glucose uptake, assessed by microPET imaging). These results could suggest that tactile and/or chemical stimuli from the mother and littermates carry relevant information for the proper development of the central nervous system, particularly in brain areas involved with emotions and social relationships of the rat. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1413-1429, 2017.

Targeting Metabolic Remodeling in Triple Negative Breast Cancer in a Murine Model.

Background: Chemotherapy is the backbone of systemic treatment for triple negative breast cancer (TNBC), which is one of the most relevant breast cancers molecular types due to the ability of tumor cells to develop drug resistance, highlighting the urgent need to design newer and safer drug combinations for treatment. In this context, to overcome tumor cell drug resistance, we employed a novel combinatorial treatment including Doxorubicin, Metformin, and Sodium Oxamate (DoxMetOx). Such pharmacological combination targets indispensable hallmarks of cancer-related to aerobic glycolysis and DNA synthesis. Materials and Methods: Thirty-five female nude mice were transplanted subcutaneously with MDA-MB-231 triple negative human cancer cell line. Once tumors were visible, mice were treated with doxorubicin, metformin, oxamate or all possible pharmacologic combinations. Treatments were administered daily for 15 days and tumors were measured by calipers every day. MicroPET images were taken in three different occasions, basal state, in the middle of the treatment, and at the end of treatment. Western blot analyses, qRT-PCR, flow cytometry, and cytotoxicity assays were performed to elucidate the mechanism of cell death promoted by the drugs in vitro. Results: In this work we assessed the proof of concept of metabolic correction in solid tumors as an effective drug treatment; hence, mice bearing tumors treated with the DoxMetOx therapy showed a complete inhibition of the tumor mass growing in 15 days of treatment depicted by the micro PET images. In vitro studies displayed that the three drugs together act by inhibiting both, mTOR-phosphorylation and expression of LDH-A gene, promoting apoptosis via dependent on the caspase-3 pathway, accompanied by cleavage of PARP. Moreover, induction of autophagy process was observed by the accumulation of LC3-II, a primordial protein implicated in the conformation and elongation of the autophagolysosome. Conclusions: The lack of effective drugs to inhibit TNBC growth is the main cause of therapy failure and tumor relapse. We have showed that targeting crucial molecular pathways in cancer by the combination of Doxorubicin, Metformin, and Oxamate resulted as an efficient and rapid tumor growth inhibitor in a triple negative xenograft model. Our findings are promising for patients diagnosed with TNBC tumors, for which unfortunately there are no reliable drug therapies.

Biodistribution in rats and estimates of doses to humans from (64)CuCl2, a potential theranostic tracer.

The aim of this study was to obtain data on the biodistribution of (64)CuCl2 in rats and to obtain estimates of the radiation doses to humans by extrapolating the animal data. MicroPET imaging and biodistribution studies were carried out with Wistar rats, and the doses were estimated with OLINDA/EXM. The lower large intestine wall was found to be the critical organ with an absorbed dose of 139±34 and 125±32µGy/MBq for females and males, respectively. The corresponding effective doses were estimated as 47±4 and 39±4µSv/MBq.

PET-Based Human Dosimetry of the Dimeric αvß3 Integrin Ligand 68Ga-DOTA-E-[c(RGDfK)]2, a Potential Tracer for Imaging Tumor Angiogenesis.

UNLABELLED: Peptides containing the Arg-Gly-Asp (RGD) sequence have high affinity for αvß3 integrin receptors overexpressed in tumor cells. The objective of this research was to determine the biodistribution and estimate the radiation dose from (68)Ga-DOTA-E-[c(RGDfK)]2 using whole-body PET scans in humans. METHODS: Five healthy volunteers (2 women, 3 men; mean age ± SD, 37.2 ± 15.6 y; range, 28-65 y; mean weight, 79.2 ± 21.0 kg; range, 64-115 kg) were included. After intravenous injection of the tracer (198.3 ± 3.3 MBq), 3 successive whole-body (vertex to mid thigh) PET/CT scans at 3 time points (30, 60, and 120 min) were obtained on a 16-slice PET/CT scanner. The subjects did not void the bladder until the entire series of images was completed. Low-dose CT without contrast agent was used for anatomic localization and attenuation correction. OLINDA/EXM software was applied to calculate human radiation doses using the reference adult model. RESULTS: The highest uptake was in the urinary bladder, followed by the liver, kidneys, and spleen, in descending order. The critical organ was the urinary bladder wall. The mean effective doses (all subjects, men and women) were 34.1 ± 4.9, 31.0 ± 2.4, and 20.9 ± 5.2 µSv/MBq for the no-voiding, 2.5-h-voiding, and 1-h-voiding models, respectively. CONCLUSION: Of particular interest in this research was the visualization of the choroid plexus and ventricular system, which seems to be a characteristic of RGD-dimeric peptides. Measured absorbed doses and effective doses are comparable to other previously reported RGD-based radiopharmaceuticals labeled with (68)Ga and (18)F. Therefore, (68)Ga-DOTA-E-[c(RGDfK)]2 can safely be used for imaging integrin αVß3 expression.

Metabolic Changes Induced by Electrical Stimulation of Prelemniscal Radiations for the Treatment of Parkinson Disease.

OBJECTIVE: The aim of this work was to study mechanisms of action of electrical stimulation of prelemniscal radiations (Raprl) in the treatment of Parkinson disease, using 2-deoxy-2-fluoro-D-glucose (18F-FDG) Positron Emission Tomography (PET/CT). Materialand Methods: Five patients with PD and predominant unilateral tremor, rigidity and bradykinesia underwent deep brain stimulation (DBS) in contralateral Raprl that improved symptoms from 82.4 to 94.5%. 18F-FDG PET studies were performed before electrode implantation and after DBS therapy. Changes in metabolic activity in PET were evaluated by the maximal standardized uptake value (MSUV) and statistical parametric mapping (SPM) for regions of interest (ROIs) ipsilateral and contralateral to the stimulation site. ROIs were derived from a preoperative probabilistic tractography and included primary motor, supplementary motor and orbitofrontal cortices: Raprl, ventrolateral thalamus, putamen and cerebellum. RESULTS: No significant MSUV changes occurred in ROIs contralateral to Raprl-DBS. In contrast, MSUV decreased ipsilateral to DBS in Raprl, the thalamus, and the primary and supplementary motor cortices. SPM analysis showed metabolic changes which were significantly different after DBS therapy in all ROIs ipsilateral to DBS compared to those in the contralateral side. CONCLUSION: Raprl-DBS decreases the metabolic activity of areas anatomically related to its fiber composition. Improvement of symptoms may result from a decrease in pathological overactivity of circuits related to the ROIs.

A simple and efficient method of nickel electrodeposition for the cyclotron production of (64)Cu.

Nickel targets for the cyclotron production of (64)Cu were prepared by electrodeposition on a gold backing from nickel chloride solutions using boric acid as buffer. Parameters studied were nickel chloride and boric acid concentration, temperature and current density. All plating conditions studied were successful obtaining efficiencies of approximately 90% in 2-3 h, reaching almost quantitative plating (>97%) in 10-20 h depending on the current density. All plated targets withstood proton irradiations up to 40 µA for 2 h. Recovered nickel was successfully recycled and reused with an overall efficiency >95%.

A quantitative and comparative study of radionuclidic and chemical impurities in water samples irradiated in a niobium target with Havar vs. niobium-sputtered Havar as entrance foils.

Enriched and natural abundance water samples were irradiated in a niobium (Nb) chamber target with Havar and Nb-sputtered Havar foils. Irradiations were performed with 17.5MeV protons at currents from 35 to 100microA lasting for 1-2.5h. Radionuclidic and chemical (cationic) impurities were determined via gamma spectroscopy and ICP-MS, respectively. Anionic impurities were evaluated by ion chromatography. Impurities in water samples irradiated with the Havar-Nb foils were much lower than the samples irradiated with an unmodified Havar foil. No significant differences were observed in the impurity levels between samples of H(2)(18)O-enriched and natural abundance water. Radionuclidic impurities were observed to decrease after 3-4 irradiations on a fresh Havar entrance foil, and reached a constant value for subsequent irradiations with the same integrated current. For targets covered with Havar foil, radionuclidic impurities were found to be proportional to the beam-integrated current regardless of the beam power and, unexpectedly, dependant of the beam power when using a Havar-Nb foil.

Production and separation of non-carrier-added 86Y from enriched 86Sr targets.

The metallic radionuclide (86)Y was produced by irradiation of enriched (86)SrCO(3) on a low-energy proton-only cyclotron. Irradiations up to 20 microA for 2h were performed with 11 MeV protons using a water-cooled target mounting with circulating chilled helium. Experimental thick target yields of 26.7 mCi/microA yielded 24 mCi of (86)Y in 2h of bombardment at 10 microA. The difference in solubility products between Y(OH)(3) and Sr(OH)(2) allows the separation of (86)Y from an alkaline strontium solution by using filter paper with an overall yield of 88 +/- 3%. The concentration of Sr in the final product was found to be on the order of 15 ppm when using 200mg of target material as determined by ICP-MS analysis. The reactivity of (86)Y was determined to be on the order of 1.5 +/- 0.8 Ci/micromol of DOTA. The enriched target material was recovered and converted to its original chemical form with an overall efficiency >90%.

Simultaneous production of high specific activity 64Cu and 61Co with 11.4 MeV protons on enriched 64Ni nuclei.

The (64)Cu and (61)Co radionuclides were produced simultaneously by irradiation of enriched (64)Ni on a low energy proton-only cyclotron. Nickel targets were prepared by electrodeposition of enriched (64)Ni (>95%) on Au backing at thicknesses of 25-225 mg/cm(2) with efficiencies >99%. Irradiations up to 30 microA for 8h were performed with 11.4 MeV protons using a water-cooled target mounting. Radiochemical separation of (64)Cu and (61)Co from (64)Ni was performed by chromatography of the chlorocomplexes in a single step using an anion exchange resin column with a yield >95%. Using this method, the Ni target material was recovered and re-plated for subsequent production runs with an overall efficiency >96%. The excitation function for the (64)Ni(p,n)(64)Cu reaction was measured and compared with published values. Experimental thick target saturation yields of 159 mCi/microA for (64)Cu and 715 microCi/microA for (61)Co were achieved. Typical specific activities of (64)Cu were found to be 18.8+/-3.3 Ci/micromol.

Positron-emitting resin microspheres as surrogates of 90Y SIR-Spheres: a radiolabeling and stability study.

Commercially available resin microspheres and SIR-Spheres were labeled with metallic positron emitters and evaluated as positron emission tomography (PET) imaging surrogates of (90)Y SIR-Spheres. Radiolabeling was performed using a batch method, and in vitro stability over 24 h was evaluated in saline at physiological pH at 37 degrees C. The activity per microsphere distribution, as evaluated by autoradiography, showed the activity per microsphere to be proportional to the square radius of the spheres, suggesting surface binding. The in vivo stability of radiolabeling was evaluated in rats by micro-PET imaging after the intravenous injection of labeled microspheres. The different resin microspheres and radionuclides evaluated in this study all showed good radiolabeling efficiency and in vitro stability. However, only resins labeled with (86)Y and (89)Zr proved to have the in vivo stability required for clinical applications.