Note: This is not a comprehensive list of publications related to the DOE IP. Our list attempts to capture all publications from 2019 and beyond.
Lu-177-based, targeted radiotherapeutics/endoradiotherapies are an emerging clinical tool for the management of various cancers. The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) remains the workhorse for such applications but can limit apparent molar activity or efficient charge modulation, which can impact target binding and, as a consequence, target efficacy. Previously, our lab had developed the small, rare earth selective bifunctional chelator, picaga, as an efficient bifunctional chelator for scandium and lutetium isotopes. Here, we assess the performance of these constructs for therapy in prostate-specific membrane antigen (PSMA)-expressing tumor xenografts. To assess the viability of picaga conjugates in conjunction with long in vivo circulation, a picaga conjugate functionalized with a serum albumin binding moiety, 177Lu-picaga-Alb53-PSMA, was also synthesized. A directly comparative, low, single 3.7 MBq dose treatment study with Lu-PSMA-617 was conducted. Treatment with 177Lu-picaga-Alb53-PSMA resulted in tumor regression and lengthened median survival (54 days) when compared with the vehicle (16 days), 47Sc-picaga-DUPA-, 177Lu-picaga-DUPA-, and 177Lu-PSMA-617-treated cohorts (21, 23, and 21 days, respectively).
The newest radioisotope for brachytherapy treatment of prostate cancer is 131Cs (t1/2 = 9.69 d, 100% EC). Generated via electron capture decay of 131Ba (t1/2 = 11.6 d, 100% EC), 131Cs has been used in brachytherapy for prostate cancer since 2004. The 131Ba parent is produced through neutron capture of enriched 130Ba in a nuclear reactor. For large-scale production of 131Ba, an accurate knowledge of production and burnup cross sections of 131Ba are essential. In this paper, we report two group cross sections (thermal and resonance integrals) for 130Ba and 131Ba and a new measure of the half-life of 131Ba. Targets consisting of milligram quantities of enriched 130Ba (∼35%) were irradiated in Oak Ridge National Laboratory's High Flux Isotope Reactor at thermal and resonance neutron fluxes of (1.9–2.1) × 1015 and (5.8–7.0) × 1013 neutrons·cm−2 s−1, respectively, for durations ranging from 3 to 26 days. In addition, cadmium covered samples of 130Ba were irradiated for 1 hour at 12.6% full reactor power (10.7 MW). The yield of 131Ba approaches a saturation value of ∼60 GBq (∼1.6 Ci) per mg of 130Ba for 20 days irradiation at a thermal neutron flux of 1.8 × 1015 n·s−1·cm−2, with a thermal/epithermal ratio of ∼30. Under the above experimental conditions, the two group cross sections of 130Ba are 6.9 ± 0.5 b (thermal, σ0) and 173 ± 7 b (resonance, I0). These values represent the sum of cross sections to metastable and ground states of 131Ba. For 131Ba, the empirically measured thermal cross section is 200 ± 50 b assuming an I0/σ0 of 10. This cross section is reported for the first time. Further, the half-life of 131Ba was remeasured to be 11.657 ± 0.008 d. Lastly, this study also resulted in the co-production of 133Ba (t1/2 = 10.52 y, 100% EC). The experimental yield of 133Ba is ∼370 MBq (∼10 mCi) per mg of 132Ba (thin target) for one cycle irradiation in the High Flux Isotope Reactor, and measured two-group 132Ba cross sections are 7.2 ± 0.2 b and 39.9 ± 1.3 b. These values also represent the sum of cross sections to metastable and ground states of 133Ba.
Recent events in America in 2020 have stimulated a worldwide movement to dismantle anti-Black racism in all facets of our lives. Anti-Black racism is, as defined by the Movement for Black Lives, a “term used to specifically describe the unique discrimination, violence, and harm imposed on and impacting Black people specifically.” In science, technology, engineering, and mathematics (STEM), we have yet to achieve the goal and responsibility to ensure that the field reflects the diversity of our lived experiences. Members of the Women in Molecular Imaging Network (WIMIN) have come together to take a stand on diversity, equity, and inclusion in the field of molecular imaging. We strongly condemn oppression in all its forms and strive to identify and dismantle barriers that lead to inequities in the molecular imaging community and STEM as a whole. In this series coined “Visions” (Antiracism and Allyship in Action), we identify and discuss specific actionable items for improving diversity and representation in molecular imaging and ensuring inclusion of all members of the community, inclusive of race, disability, ethnicity, religion, or LGBTQ+ identity. Although the issues highlighted here extend to other under-recruited and equity-seeking groups, for this first article, we are focusing on one egregious and persistent form of discrimination: anti-Black racism. In this special article, Black women residing in America present their lived experiences in the molecular imaging field and give candid insights into the challenges, frustrations, and hopes of our Black friends and colleagues. While this special article focuses on the experiences of Black women, we would like the readers to reflect on their anti-Blackness toward men, transgender, nonbinary, and gender non-conforming people. From the vulnerability we have asked of all our participants, these stories are meant to inspire and invoke active antiracist work among the readership. We present strategies for dismantling systemic racism that research centers and universities can implement in the recruitment, retention, mentorship, and development of Black trainees and professionals. We would like to specifically acknowledge the Black women who took the time to be interviewed, write perspectives, and share their lived experiences in hopes that it will inspire genuine and lasting change.
A number of accelerator-based isotope production facilities utilize 100- to 200-MeV proton beams due to the high production rates enabled by high-intensity beam capabilities and the greater diversity of isotope production brought on by the long-range of high-energy protons. However, nuclear reaction modeling at these energies can be challenging because of the interplay between different reaction modes and a lack of existing guiding cross-section data.
Molecular imaging is a non-invasive process that enables the visualization, characterization, and quantitation of biological processes at the molecular and cellular level. With the emergence of theragnostic agents to diagnose and treat disease for personalized medicine there is a growing need for matched pairs of isotopes. Matched pairs offer the unique opportunity to obtain patient specific information from SPECT or PET diagnostic studies to quantitate in vivo function or receptor density to inform and tailor therapeutic treatment. There are several isotopes of arsenic that have emissions suitable for either or both diagnostic imaging and radiotherapy. Their half-lives are long enough to pair them with peptides and antibodies which take longer to reach maximum uptake to facilitate improved patient pharmacokinetics and dosimetry then can be obtained with shorter lived radionuclides. Arsenic-72 even offers availability from a generator that can be shipped to remote sites and thus enhances availability. Arsenic has a long history as a diagnostic agent, but until recently has suffered from limited availability, lack of suitable chelators, and concerns about toxicity have inhibited its use in nuclear medicine. However, new production methods and novel chelators are coming online and the use of radioarsenic in the pico and nanomolar scale is well below the limits associated with toxicity. This manuscript will review the production routes, separation chemistry, radiolabeling techniques and in vitro/in vivo studies of three medically relevant isotopes of arsenic (arsenic-74, arsenic-72, and arsenic-77).
Targeted alpha therapy (TAT) is an area of research with rapidly increasing importance as the emitted alpha particle has a significant effect on inducing cytotoxic effects on tumor cells while mitigating dose to normal tissues. Two significant isotopes of interest within the area of TAT are thorium-227 and actinium-225 due to their nuclear characteristics. Both isotopes have physical half-lives suitable for coordination with larger biomolecules, and additionally actinium-225 has potential to serve as an in vivo generator. In this review, the authors will discuss the production, purification, labeling reactions, and biological studies of actinium-225 and thorium-227 complexes and clinical studies.
“Isotope harvesting” is a technique that offers access to exotic radionuclides created as by-products during nuclear science research. Ongoing exploratory work at the National Superconducting Cyclotron Laboratory (NSCL) is directed towards the production and extraction of rare radionuclides from a flowing-water target and intends to pave the way for future harvesting efforts at the upcoming Facility for Rare Isotope Beams (FRIB). Here we present the collection of 62Zn from an aqueous matrix irradiated with a 150 MeV per nucleon 78Kr beam, while synergistically capturing other gaseous reaction products. In addition to the production rate for 62Zn (9.08(30) × 10−5 62Zn per incoming 78Kr), the rates of formation for several other radionuclides were determined as well. The purification of 62Zn from a large number of co-produced radionuclides was performed by anion exchange chromatography, allowing the isolation of 80.5(5.2)% of the generated 62Zn. With the decay of 62Zn the radioactive daughter 62Cu is generated, and with the isolation of pure 62Cu eluate, the principle of a medical radionuclide generator could be demonstrated. To illustrate the applicability of the obtained 62Zn, the isolated product was used in free and DTPA-labelled form in a proof of principle plant uptake study with garden cress employing phosphor imaging for visualization.
An experiment was performed at the National Superconducting Cyclotron Laboratory using a 140 MeV/nucleon 48Ca beam and a flowing-water target to produce 47Ca for the first time with this production route. A production rate of 0.020 ± 0.004 47Ca nuclei per incoming beam particle was measured. An isotope harvesting system attached to the target was used to collect radioactive cationic products, including 47Ca, from the water on a cation-exchange resin. The 47Ca collected was purified using three separation methods optimized for this work: (1) DGA extraction chromatography resin with HNO3 and HCl, (2) AG MP-50 cation-exchange resin with an increasing concentration gradient of HCl, and (3) AG MP-50 cation-exchange resin with a methanolic HCl gradient. These methods resulted in ≥99 ± 2% separation yield of 47Ca with 100% radionuclidic purity within the limits of detection for HPGe measurements. Inductively coupled plasma-optical emission spectrometry (ICP-OES) was used to identify low levels of stable ions in the water of the isotope harvesting system during the irradiation and in the final purified solution of 47Ca. For the first time, this experiment demonstrated the feasibility of the production, collection, and purification of 47Ca through isotope harvesting for the generation of 47Sc for nuclear medicine applications.
A high-intensity proton irradiation was performed with the flowing-water isotope harvesting target at the University of Wisconsin-Madison Cyclotron Laboratory to measure the rate of degradation of the target shell during irradiation conditions. The beam reached an intensity of 34 µA by the end of the irradiation and covered an area of 0.7 cm2 on the target. Radiolysis products, such as H2O2, H2, and O2, were measured in the bulk water of the system and found to be present at much lower levels than predicted by literature escape yields. Radionuclides formed in the target shell were measured in the system water as a radiotracer for target degradation. Using a simple, beam intensity-dependent model, a corrosion rate of 1.5E-6 μm/(μA*s) was found to match the measured radiotracer activities at various points in the irradiation. This rate was used to extrapolate the lifetime of future isotope harvesting targets at the NSCL and FRIB, using the areal power density of different ion beams to scale the corrosion rate.
The Nuclear Medicine Global Initiative (NMGI) was formed in 2012 by 13 international organizations to promote human health by advancing the field of nuclear medicine and molecular imaging by supporting the practice and application of nuclear medicine. The first project focused on standardization of administered activities in pediatric nuclear medicine and resulted in two manuscripts. For its second project the NMGI chose to explore issues impacting on access and availability of radiopharmaceuticals around the world. Methods: Information was obtained by survey responses from 35 countries on available radioisotopes, radiopharmaceuticals and kits for diagnostic and therapeutic use. Issues impacting on access and availability of radiopharmaceuticals in individual countries were also identified. Results: Detailed information on radiopharmaceuticals utilized in each country, and sources of supply, was evaluated. Responses highlighted problems in access particularly due to the reliance on a sole provider, regulatory issues and reimbursement, as well as issues of facilities and workforce particularly in low- and middle-income countries. Conclusion: Strategies to address access and availability of radiopharmaceuticals are outlined, to enable timely and equitable patient access to nuclear medicine procedures worldwide. In the face of disruptions to global supply chains by the COVID-19 outbreak, renewed focus on ensuring reliable supply of radiopharmaceuticals is a major priority for nuclear medicine practice globally.
