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Separation of 225Ra (t1/2 = 15 d) from its daughter isotope 225Ac (t1/2 = 10 d) is necessary to obtain pure 225Ac for cancer alpha-therapy. In this study, microscale separation of 225Ra from its da...

In this paper, we describe the 147Pm production yields and level of impurities from several targets that consisted of milligram quantities of highly enriched 146Nd oxide irradiated at the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory for durations ranging from 24 to 180 h. A comparison between theoretical and experimental data are also presented, and attempts were made to empirically evaluate the neutron capture cross-sections of 41.3-d 148mPm and 5.4-d 148gPm. For a one-cycle irradiation (~24 days), 147Pm yield reaches a maximum value of 101.8 MBq/mg (2.75 mCi/mg) at 60 days after the end of bombardment. Because of large neutron capture cross-sections of 147Pm, the yield of 147Pm does not significantly increase with longer irradiation. Our estimates of the thermal neutron capture cross-section and resonance integral for 146Nd at 1.48 ± 0.05 b and 2.56 ± 0.25 b, respectively, were consistent with the reported values. The effective neutron capture cross-section of 147Pm to 148mPm was 53.3 ± 2.7 b–a factor of 2 lower than the 98.7 ± 6.5 b calculated from reported cross-sections. The measured σeff to the ground state (5.37-d 148gPm) was 82.0 ± 4.1 b; ~34% lower than the value of 139 ± 10 b calculated from reported cross-sections. In this work, we also describe the development of a chemical process based on extraction and ion-exchange chromatography for separation of 147Pm from milligram quantities of 146Nd and other impurities. Sequential separation of Pm from the Nd target and from other radioisotopic impurities (153Gd and 154&155Eu, 192Ir, and 60Co) was achieved using a LN extraction resin in HCl media followed by further purification of Pm from 60Co and 192Ir using a low cross-linking cation exchange resin. Based on these data, we estimated that two rounds of purification under our experimental conditions can provide a mass separation factor of >104 between Pm and Nd. Our data indicate that curie quantities of 147Pm with suitable chemical and radioisotopic purity for applications in beta voltaic batteries can be produced by irradiating gram quantities of highly enriched 146Nd in the flux trap of HFIR for one cycle.

A search for production of the superheavy elements with atomic numbers 119 and 120 was performed in the 50Ti+249Bk and 50Ti+249Cf fusion-evaporation reactions, respectively, at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. Over four months of irradiation, the 249Bk target partially decayed into 249Cf, which allowed for a simultaneous search for both elements. Neither was detected at cross-section sensitivity levels of 65 and 200 fb for the 50Ti+249Bk and 50Ti+249Cf reactions, respectively, at a midtarget beam energy of Elab=281.5 MeV. The nonobservation of elements 119 and 120 is discussed within the concept of fusion-evaporation reactions including various theoretical predictions on the fission-barrier heights of superheavy nuclei in the region of the island of stability. peerReviewed

Purification of berkelium-249 (249Bk) at Oak Ridge National Laboratory requires a multi-step process with Bk Finishing as the final step. The current multi-process takes 6–7 months, including ~ 3 months spent on Bk Finishing. Recent trials of using columns of either LN resin or MP-1 anion exchange resin adsorbing the tetravalent 249Bk4+ in 8M HNO3-0.5M NaBrO3, followed by eluting impurities (e.g. Ce4+, Cf3+) and stripping 249Bk resulted in a new dual column method of selectively separating 249Bk from other trans-curium elements and fission product impurities, which is proposed to replace the current Bk Finishing with higher Bk purification efficiency and shorter processing period. This paper displays the experimental results and describes the dual column method with relevant chemistry issues.

The heaviest currently known nuclei, which have up to 118 protons, have been produced in 48Ca induced reactions with actinide targets. Among them, the element tennessine (Ts), which has 117 protons, has been synthesized by fusing 48Ca with the radioactive target 249Bk, which has a half-life of 327 d. The experiment was performed at the gas-filled recoil separator TASCA. Two long and two short α decay chains were observed. The long chains were attributed to the decay of 294Ts. The possible origin of the short-decay chains is discussed in comparison with the known experimental data. They are found to fit with the decay chain patterns attributed to 293Ts. The present experimental results confirm the previous findings at the Dubna Gas-Filled Recoil Separator on the decay chains originating from the nuclei assigned to Ts.

Electroplated depositions of Sm were prepared using a vertical well-type electrodeposition unit with an aqueous ammonium acetate electrolyte system, with an average deposition yield just over 87%. The depositions were analyzed for morphology and thickness by scanning electron microscopy (SEM) and chemical composition by energy dispersion X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) before and after firing. The depositions were fired at 125–700 °C, while varying the heating rate from 0.5 to 10 °C/min in either an oxidizing or reducing atmosphere. A heating rate of 10 °C/min was slow enough to prevent disruption of the deposition morphology during firing. A gas sweep enhanced the removal of any organic substituents, with an oxidizing environment being more advantageous than a reducing environment.

Characterization of a samarium thin film deposited on a stainless steel substrate using electrodeposition was carried out with a Thermo Scientific K-Alpha X-ray photoelectron spectrometer. Two types of samarium electrodeposition samples were studied, one as-deposited and one heated to 700 °C in an air atmosphere. Survey scans include peaks coming from the stainless steel substrate, such as Fe and Cr. An x-ray photoelectron spectroscopy (XPS) survey spectrum, Sm 3d, C 1s, and O 1s narrow scans are shown. It was determined, using XPS, that the heating process decomposed the deposited Sm acetate to Sm2O3.

Samarium thin-films doped with a 252 Cf radiotracer were used to study the effects of annealing on the release of fission fragments from electrodeposited films. An ammonium acetate molecular plating technique was utilized to perform the depositions. The fission fragment yields were measured using a unique technique involving the exposure of aluminum foils to the deposited material for a fixed time followed by gamma-ray spectroscopy to determine the rate at which the fission fragments implanted into the foils. Annealing of the electrodeposited films was found to have no effect on the release of fission fragments.

The search for new decay chains of oganesson isotopes is presented. The experiment utilized the Dubna Gas Filled Recoil Separator and a highly segmented recoil-decay detection system. The signals from all detectors were analyzed in parallel by digital and analog data acquisition systems. For the first time, a target of mixed californium (51% Cf249, 13% Cf250, and 36% Cf251) recovered from decayed Cf252 sources was produced and irradiated with an intense Ca48 beam. The observation of a new decay chain of Og294 is reported. The prospects for reaching new isotopes Og295,296 are discussed.

Since 2000, six new super-heavy elements with atomic numbers 113 through 118 have been synthesized in hot fusion reactions of 48Ca beams on actinide targets. These target materials, including 242Pu, 244Pu, 243Am, 245Cm, 248Cm, 249Cf, and 249Bk, are available in very limited quantities and require specialized production and processing facilities resident in only a few research centers worldwide. This report describes the production and chemical processing of heavy actinide materials for super-heavy element research, current availabilities of these materials, and related target fabrication techniques. The impact of actinide materials in super-heavy element discovery is reviewed, and strategies for enhancing the production of rare actinides including 249Bk, 251Cf, and 254Es are described.

Electrodeposition is a technique routinely employed in nuclear research for the preparation of thin solid films of actinide materials used in accelerator beam bombardments, irradiation studies, or as radioactive sources. This study investigates the deposition of both lanthanides and actinides from an aqueous ammonium acetate electrolyte matrix. Electrodepositions were performed primarily on stainless steel disks, with yield analysis evaluated using γ-spectroscopy. Experimental parameters (run time, current density, voltage, electrolyte concentration, and initial analyte mass) were studied and modified to optimize the uniformity and adherence of the deposition while maximizing yield. The procedure utilized samarium as the plating material, both with and without a radioactive tracer. Surface characterization studies were performed by scanning electron microscopy, electron microprobe analysis, radiographic imaging, and x-ray diffraction.

Electrodepositions of californium isotopes were successfully performed at Oak Ridge National Laboratory involving two different types of deposition solutions, ammonium acetate and isobutanol. A californium product that was decay-enriched in 251Cf was recovered for use in super-heavy element research. The californium was purified and then electrodeposited using the isobutanol method onto thin titanium foils for use at the Joint Institute for Nuclear Research. An ammonium acetate method was used to produce a deposition containing 1.7 ± 0.1 Ci of 252Cf onto a stainless steel substrate. This is the largest single electrodeposition of 252Cf ever prepared.

A new method has been developed for the isolation of 223,224,225Ra, in high yield and purity, from a proton irradiated 232Th matrix. Herein we report an all-aqueous process using multiple solid-supported adsorption steps including a citrate chelation method developed to remove >99.9% of the barium contaminants by activity from the final radium product. A procedure involving the use of three columns in succession was developed, and the separation of 223,224,225Ra from the thorium matrix was obtained with an overall recovery yield of 91 ± 3%, average radiochemical purity of 99.9%, and production yields that correspond to physical yields based on previously measured excitation functions.

The staff at the Radiochemical Engineering Development Center, located at Oak Ridge National Laboratory, produced a 6.3 ± 0.4 GBq (1.7 ± 0.1 Ci) 252Cf source for the Californium Rare Isotope Breeder Upgrade (CARIBU) project at Argonne National Laboratory’s Argonne Tandem Linac Accelerator System. The source was produced by electrodeposition of a 252Cf sample onto a stainless steel substrate, which required material free from excess mass for efficient deposition. The resulting deposition was the largest reported 252Cf electrodeposition source ever produced. Several different chromatographic purification methods were investigated to determine which would be most effective for final purification of the feed material used for the CARIBU source. The separation of lanthanides from the Cf was of special concern. The separation, using 145Sm, 153Gd, and 249Cf as tracers, was investigated using BioRad AG 50X8 in α-hydroxyisobutyric acid, Eichrom LN resin in both HNO3 and HCl, and Eichrom TEVA resin in NH4SCN. The TEVA NH4SCN system was found to completely separate 145Sm and 153Gd from 249Cf and was adopted into the purification process used in purifying the 252Cf.

New separation methodologies for radioisotopes are crucial to many medical applications. In this work, the solvent extraction of Th-227 and Ac-225 based on ionic liquids (ILs) was investigated usingN,N,N´,N´-tetraoctyldiglycolamide (TODGA) or di(2-ethylhexyl)phosphoric acid (HDEHP) as an extractant. Four ILs, 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([C4mim][NTf2]), 1-butyl-3-methylimidazolium bis(perfluoroethanesulfonyl)imide ([C4mim][BETI]), 1-butyl-2,3-trimethyleneimidazolium (trifluoromethanesulfonyl)imide ([BuI5][NTf2]), and 1-benzyl pyridinium bis(trifluoromethanesulfonyl)imide ([PhCH2Py][NTf2]) with different cation or anion structural features were used as diluents for the separation of Th-227 and Ac-225. Excellent extraction efficiencies and selectivities were found for Th-227/Ac-225 when HDEHP was used as an extractant in these ILs. The effects of different extractant concentrations in ILs and different aqueous phase acidities on extraction efficiencies and selectivities of Th-227/Ac-225 are also presented. The success in separation of Th-227 and Ac-225 isotopes highlights great potentials of use of ionic liquids in isotope production.

Characterization of samarium thin films molecular plated from N,N-dimethylformamide solutions onto stainless steel substrates, with either mirrorlike or brushed finishes, was carried out using a Thermo Scientific K-Alpha x-ray photoelectron spectrometer. Survey scans of the two specimens showed the presence of samarium, carbon, and oxygen with minor amounts of sodium. High-resolution spectra were then taken of the Sm 3d, O 1s, and C 1s regions. The chemical compositions of the two samples were found to be very similar, with the key difference being the relative amounts of two carbon species. Spectra from the survey and narrow high-resolution scans of the Sm 3d, O 1s, and C 1s regions are reported herein.Characterization of samarium thin films molecular plated from N,N-dimethylformamide solutions onto stainless steel substrates, with either mirrorlike or brushed finishes, was carried out using a Thermo Scientific K-Alpha x-ray photoelectron spectrometer. Survey scans of the two specimens showed the presence of samarium, carbon, and oxygen with minor amounts of sodium. High-resolution spectra were then taken of the Sm 3d, O 1s, and C 1s regions. The chemical compositions of the two samples were found to be very similar, with the key difference being the relative amounts of two carbon species. Spectra from the survey and narrow high-resolution scans of the Sm 3d, O 1s, and C 1s regions are reported herein.

The initial clinical trials for treatment of acute myeloid leukemia have demonstrated the effectiveness of the alpha emitter (213)Bi in killing cancer cells. Bismuth-213 is obtained from a radionuclide generator system from decay of 10-days (225)Ac parent. Recent pre-clinical studies have also shown the potential application of both (213)Bi, and the (225)Ac parent radionuclide in a variety of cancer systems and targeted radiotherapy. This paper describes our five years of experience in production of (225)Ac in partial support of the on-going clinical trials. A four-step chemical process, consisting of both anion and cation exchange chromatography, is utilized for routine separation of carrier-free (225)Ac from a mixture of (228)Th, (229)Th and (232)Th. The separation of Ra and Ac from Th is achieved using the marcoporous anion exchange resin MP1 in 8M HNO(3) media. Two sequential MP1/NO(3) columns provide a separation factor of approximately 10(6) for Ra and Ac from Th. The separation of Ac from Ra is accomplished on a low cross-linking cation exchange resin AG50-X4 using 1.2M HNO(3) as eluant. Two sequential AG50/NO(3) columns provide a separation factor of approximately 10(2) for Ac from Ra. A 60-day processing schedule has been adopted in order to reduce the processing cost and to provide the highest levels of (225)Ac possible. Over an 8-week campaign, a total of approximately 100 mCi of (225)Ac (approximately 80% of the theoretical yield) is shipped in 5-6 batches, with the first batch typically consisting of approximately 50 mCi. After the initial separation and purification of Ac, the Ra pool is re-processed on a bi-weekly schedule or as needed to provide smaller batches of (225)Ac. The averaged radioisotopic purity of the (225)Ac was 99.6 +/- 0.7% with a (225)Ra content ofor =0.6%, and an average (229)Th content of (4(-4)(+5)) x 10(-5)%.

The superheavy element with atomic number Z=117 was produced as an evaporation residue in the 48Ca+249Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The radioactive decay of evaporation residues and their α-decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-μs and a few days. Two decay chains comprising seven α decays and a spontaneous fission each were identified and are assigned to the isotope 294-117 and its decay products. A hitherto unknown α-decay branch in 270Db (Z=105) was observed, which populated the new isotope 266Lr (Z=103). The identification of the long-lived (T1/2=1.0+1.9−0.4 h) α-emitter 270Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an “island of stability.” (Less)

The reaction of 249 Bk with 48 Ca have been reinvestigated to provide new evidence for the discovery of element 117 on a larger number of events. The experiments were performed at five projectile energies and with a total beam dose of 48 Ca of about 4.6×10 19 . Two isotopes 293,294 117 were synthesized in the 249 Bk+ 48 Ca reaction, providing excitation functions and α-decay spectra of the produced isotopes that establishes these nuclei to be the products of the 4n- and 3n-evaporation channels, respectively. Decay properties of 293,294 117 and of all the daughter products agree with the data of the experiment in which these nuclei were synthesized for the first time in 2010. The new 289 115 events, populated by α decay of 293 117, demonstrate the same decay properties as those observed for 289 115 produced in the 243 Am( 48 Ca,2n) reaction thus providing cross- bombardment evidence. In addition, a single decay of 294 118 was observed from the reaction with 249 Cf - a result of the in-growth of 249 Cf in the 249 Bk target.

Rat MAb 201B, which binds to murine thrombomodulin, can deliver up to 50% of the injected dose of attached radioisotopes to the lung vascular endothelium. We have shown previously that intravenous injection of about 30 microCi of 213Bi-MAb 201B, which delivers about 15 Gy of alpha irradiation to the lung, is capable of eradicating small lung colonies (500-1000 cells) of the mammary tumor line, EMT-6. Larger tumors (5000 cells) were not completely cured by this vascular targeted radioimmunotherapy (VT-RAIT) approach. We reasoned that VT-RAIT might make the lung vessels serving the tumor cells more permeable, allowing MAb targeted to the tumor cells to extravasate more readily and mediate more efficient standard radioimmunotherapy (RAIT). Distribution experiments with the tumor targeted MAb 13A (RAIT MAb), following VT-RAIT, did not demonstrate a large increase in tumor uptake; however, microautoradiography did indicate that MAb 13A was distributed more evenly throughout the tumor when administered after VT-RAIT. Therapy experiments on lung tumors of approximately 5000 cells each, combining 213Bi-MAb 201B (VT-RAIT) with 213Bi-MAb 13A (RAIT) 24 hours later, resulted in a better outcome (3 cured/10 at risk) than for control groups: RAIT only (0/10), VT-RAIT only (1/10), or no therapy (0/10). RAIT therapy delivered 48 hours after VT-RAIT had no apparent benefit. 213Bi-MAb 201B VT-RAIT followed by 90Y-MAb 13A Fab' RAIT showed only a slight improvement in tumor cures (2/10) over that in control groups: (0/9), (0/10), (0/10), respectively. These results suggest that optimal timing, dosage, and choice of MAb for RAIT should enhance the double MAb therapy approach significantly.

A model system has been used to test the efficacy of vascular targeting of α-particle emitter213Bi for therapy of small, ‘artificial’ metastases in mouse lung. Specific monoclonal antibody (mAb) 201B was used to deliver greater than 30% of the injected dose to lung where tumours had developed due to intravenous injection of cells. Specific213Bi-mAb 201B treatment of BALB/c mammary carcinoma EMT-6 tumours in lung resulted in a dose-dependent destruction of tumours and an extended lifespan of treated animals relative to controls. Significant reduction of lung tumour burden was noted in animals treated with 0.93 MBq injected dose or as little as 14 Gy absorbed dose to the lung. Animals treated with higher doses (2.6–6.7 MBq) had nearly complete cure of lung tumours but eventually died of lung fibrosis induced by the treatment. Four other tumour cell types were studied: murine Line 1 lung carcinomas in syngeneic BALB/c mice, rat IC-12 tracheal carcinoma growing in severe combined immune deficient (SCID) mice, and two human tumours – epidermoid carcinoma A431 and lung carcinoma A549 – growing in SCID mice. In all cases, the number of lung tumour colonies was reduced in animals treated with specific, labelled mAb relative to those in animals treated with control213Bi MAb or EDTA complexed213Bi. Tumours treated in immunodeficient SCID mice were partially destroyed or at least retarded in growth, but ultimately regrew and proved fatal, indicating that an intact immune function is necessary for complete cure. The data show that the short-lived α-particle emitter213Bi can be effectively targeted to lung blood vessels and that tumour cells growing in the lung are killed. The mechanism may involve direct killing of tumour cells from α-particle irradiation, killing through destruction of blood supply to the tumour, or a combination of the two. © 1999 Cancer Research Campaign

This paper presents a rapid method of separation of five actinide elements (Th, U, Np, Pu, and Am) for aqueous media samples. This separation method utilizes the unique chemistries of the actinides at low concentrations1,2 and the properties of the EIChroM TRU-ResinTM extraction resin. In order to cleanly recover the five actinides from aqueous samples or solubilized soil samples, the sample is passed through the column twice. The sample is first loaded in an HCl solution with hydrogen peroxide. This allows the Am and most matrix ions to pass through the column. Then the Th is eluted using dilute HCl followed by the Np and Pu which are eluted together with oxalic acid in dilute HCl solution. Finally, the U is eluted with ammonium oxalate solution. A calcium-oxalate coprecipitation is performed on the original load solution containing the Am ions and the dissolved precipitate is then reloaded onto the TRU-ResinTM column in HNO3 with ascorbic acid. The procedure requires approximately 1.5 working days for experienced technicians, greatly reduces waste, and generally results in actinide recoveries of 80–100%.

Studies of superheavy nuclei produced in the ${}^{249}$Bk + ${}^{48}$Ca reaction were performed using the Dubna Gas Filled Recoil Separator. The cross section for the production of ${}^{293}$117 and ${}^{294}$117 isotopes was measured at five excitation energies of the ${}^{297}$117 compound nucleus ranging from 30 to 48 MeV and yielding maximum values of 1.1${}_{\ensuremath{-}0.6}^{+1.2}$ pb for the $3n$ and 2.4${}_{\ensuremath{-}1.4}^{+3.3}$ pb for the $4n$ reaction channels. Alpha emission from ${}^{281}$Rg competing with spontaneous fission ($\ensuremath{\alpha}$/SF decay probability 1:9) was observed for the first time leading to the identification of the new isotope ${}^{277}$Mt (${T}_{\mathrm{SF}}\ensuremath{\approx}5$ ms). The measured decay properties are in good agreement with those expected based on the properties of neighboring even-$Z$ and odd-$Z$ nuclei. The $\ensuremath{\alpha}$ energies and half-lives of odd-$Z$ isotopes observed in the ${}^{293}$117 and ${}^{294}$117 decay chains together with results obtained for lower-$Z$ superheavy nuclei demonstrate enhanced stability with increasing neutron number toward the predicted new magic number $N=184$.

$\ensuremath{\alpha}$ decay of ${}^{249}$Bk has been investigated by measuring its $\ensuremath{\alpha}$ and $\ensuremath{\gamma}$-ray spectra, both in singles and in coincidence modes. The $\ensuremath{\alpha}$ spectrum of a freshly purified ${}^{249}$Bk sample was measured with a high-resolution, double-focusing magnetic spectrometer. $\ensuremath{\gamma}$ singles, $\ensuremath{\gamma}$-$\ensuremath{\gamma}$ coincidence, and $\ensuremath{\gamma}$-$\ensuremath{\alpha}$ coincidence spectra were also recorded. The absolute intensity of the 327.45-keV $\ensuremath{\gamma}$ ray has been determined to be ($1.44\ifmmode\pm\else\textpm\fi{}0.08)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}5}$% per ${}^{249}$Bk decay. Assignments of previously known single-particle states were confirmed. A new rotational band was identified in the $\ensuremath{\alpha}$ singles spectrum and Am K x rays have been observed in its decay. This single-particle state, with an energy of 154 keV, has been assigned to the 3/2${}^{\ensuremath{-}}$[521] Nilsson state. This is the lowest excitation energy for this orbital in any Am nucleus. More precise energies and intensities of the ${}^{249}$Bk $\ensuremath{\alpha}$ groups and $\ensuremath{\gamma}$-ray transitions are provided.

The reaction of 249Bk with 48Ca has been investigated with an aim of synthesizing and studying the decay properties of isotopes of the new element 117. The experiments were performed at five projectile energies (in two runs, in 2009-2010 and 2012) and with a total beam dose of 48Ca ions of about 9x1019 The experiments yielded data on a-decay characteristics and excitation functions of the produced nuclei that establish these to be 293117 and 294117 – the products of the 4n- and 3n-evaporation channels, respectively. In total, we have observed 20 decay chains of Z=117 nuclides. The cross sections were measured to be 1.1 pb for the 3n and 2.4 pb for the 4n-reaction channel. The new 289115 events, populated by α decay of 117, demonstrate the same decay properties as those observed for 115 produced in the 243Am(48Ca,2n) reaction thus providing cross-bombardment evidence. In addition, a single decay of 294118 was observed from the reaction with 249Cf – a result of the in-growth of 249Cf in the 249Bk target. The observed decay chain of 294118 is in good agreement with decay properties obtained in 2002-2005 in the experiments with the reaction 249Cf(48Ca,3n)294118. The energies and half-lives of the odd-Z isotopes observed in the 117 decay chains together with the results obtained for lower-Z superheavy nuclei demonstrate enhancement of nuclear stability with increasing neutron number towards the predicted new magic number N=184.

The biodistribution and tissue toxicity of intravenously administered 225-actinium (225Ac) complexed with acetate, ethylene diamine tetraacetic acid (EDTA), 1, 4, 7, 10, 13-pentaazacyclopentadecane-N, N', N", N"', N""-pentaacetic acid (PEPA), or the "a" isomer of cyclohexyl diethylenetriamine pentaacetic acid (CHX-DTPA), were examined. The percent of injected dose per organ and per gram of tissue for each chelate complex was determined. 225Ac-CHX-DTPA was evaluated further for radiotoxic effects. Mice receiving > or =185 kBq 225Ac-CHX-DTPA suffered 100% morbidity by 5 days and 100% mortality by 8 days postinjection, and all animals evaluated had significant organ damage. The in vivo instability of the 225Ac-CHX-DTPA complex likely allowed accumulation of free 225Ac in organs, which resulted in tissue pathology.

Targeted radiotherapies maximize cytotoxicty to cancer cells. In vivo α-generator targeted radiotherapies can deliver multiple α particles to a receptor site dramatically amplifying the radiation dose delivered to the target. The major challenge with α-generator radiotherapies is that traditional chelating moieties are unable to sequester the radioactive daughters in the bioconjugate which is critical to minimize toxicity to healthy, non-target tissue. The recoil energy of the (225)Ac daughters following α decay will sever any metal-ligand bond used to form the bioconjugate. This work demonstrates that an engineered multilayered nanoparticle-antibody conjugate can deliver multiple α radiations and contain the decay daughters of (225)Ac while targeting biologically relevant receptors in a female BALB/c mouse model. These multi-shell nanoparticles combine the radiation resistance of lanthanide phosphate to contain (225)Ac and its radioactive decay daughters, the magnetic properties of gadolinium phosphate for easy separation, and established gold chemistry for attachment of targeting moieties.

Monoclonal antibody 13A to murine CD44 was used to bind the alpha-particle emitter 213Bi to cell surfaces of cultured EMT-6 or Line 1 tumor cells. Data on kinetics and saturation of binding, cell shape and nuclear size were used to calculate the absorbed dose to the nuclei. Treatment of monolayer cells with [213Bi]MAb 13A produced a classical exponential survival curve with no apparent shoulder. Microdosimetry analyses indicated that 1.4-1.7 Gy produced a 37% surviving fraction (D0). Multicellular spheroids were shown to bind [213Bi]MAb 13A mainly on the outer cell layer. Relatively small amounts of activity added to the spheroids resulted in relatively large absorbed doses. The result was that 3-6-fold less added radioisotope was necessary to kill similar fractions of cells in spheroids than in monolayer cells. These data are consistent with the interpretation that the alpha particles from a single 213Bi atom bound to one cell can penetrate and kill adjacent cells. Flow cytometry was used to sort cells originating from the periphery or from the interior of spheroids. Cells from the outside of the [213Bi]MAb 13A exposed spheroids had a lower surviving fraction per administered activity than cells from the interior. Cells were killed efficiently in spheroids up to 20-30 cells in diameter. The data support the hypothesis that alpha-particle emitters should be very efficient at killing cells in micrometastases of solid tumors.