Objective. High-energy proton irradiation of 232 Th produces both 225 Ac and its precursor 225 Ra, the latter being underexplored despite its potential applicability at relevant facilities. This study aims to provide a theoretical basis for 232 Th-based 225 Ra production by modeling the associated yields and radioisotopic impurity levels. Approach. Production yields of 225 Ra and levels of 228 Ra impurity were calculated using Monte Carlo simulations for proton energies of 100–800 MeV, total 232 Th target thicknesses of 0.125–8 mm, and an irradiation time of 15 d. A theoretical model was developed for predicting the cumulative yield of 225 Ac eluates from a 225 Ra yield. The levels of 228 Ra-derived 228 Ac impurity in 225 Ac eluates and the postelution decay times required to suppress 228 Ac to acceptable thresholds were modeled and computed. Main results. The calculated 225 Ra yields at the end of bombardment for a 15 d irradiation ranged from 2.3 ± 0.3 MBq µA −1 at 100 MeV to 563.1 ± 12.3 MBq µA −1 at 700 MeV. Increases in 225 Ra yield were most pronounced when the proton energy was raised from 100 to 200 MeV, with diminishing returns at higher energies. The cumulative yield of 225 Ac eluates was about 29.1% of a 225 Ra yield under combined conditions of hypothetical and empirical settings. Postelution times of at least 25.1–30.1 h should be allowed to reduce 228 Ac impurity levels to below 0.1%. Significance. The developed models provide a quantitative basis for evaluating and optimizing 225 Ra production via proton irradiation of 232 Th. This study quantitatively predicted the presence of 228 Ac in 225 Ac eluates under various conditions and showed how 228 Ac can be suppressed by introducing minimal postelution decay times.

Antimony-119 (119Sb) is a radionuclide of interest for targeted Auger electron therapy. Isotopically pure 119Sb can be produced by proton irradiation of enriched tin-119 (119Sn) targets in conventional widely available low energy medical cyclotrons. Enriched 119Sn is very costly ( 20,000 CAD/gram), requiring recycling of the target material to make this production route economically viable. Herein, we investigate three Sn electroplating methods, evaluate the target quality, as well as method compatibility with subsequent 119Sb radiochemical purification steps. Three electroplating bath compositions (Sn(II) sulfate, Sn(IV) sols, and Sn(IV) chloride) for Sn deposition were tested and successfully implemented. One of the methods, utilizing a Sn(IV) chloride bath solution was able to achieve quantitative electroplating efficiency (98 ± 3

Objective. High-energy proton irradiation of Th-232 produces both Ac-225 and its precursor Ra-225, the latter being underexplored despite its potential applicability at relevant facilities. This study aims to provide a theoretical basis for Th-232-based Ra-225 production by modeling the associated yields and radioisotopic impurity levels. Approach. Production yields of Ra-225 and levels of Ra-228 impurity were calculated using Monte Carlo simulations for proton energies of 100-800 MeV, total Th-232 target thicknesses of 0.125-8 mm, and an irradiation time of 15 d. A theoretical model was developed for predicting the cumulative yield of Ac-225 eluates from a Ra-225 yield. The levels of Ra-228-derived Ac-228 impurity in Ac-225 eluates and the postelution decay times required to suppress Ac-228 to acceptable thresholds were modeled and computed. Main results. The calculated Ra-225 yields at the end of bombardment for a 15 d irradiation ranged from 2.3 +/- 0.3 MBq mu A(-1) at 100 MeV to 563.1 +/- 12.3 MBq mu A(-1) at 700 MeV. Increases in Ra-225 yield were most pronounced when the proton energy was raised from 100 to 200 MeV, with diminishing returns at higher energies. The cumulative yield of Ac-225 eluates was about 29.1% of a Ra-225 yield under combined conditions of hypothetical and empirical settings. Postelution times of at least 25.1-30.1 h should be allowed to reduce Ac-228 impurity levels to below 0.1%. Significance. The developed models provide a quantitative basis for evaluating and optimizing Ra-225 production via proton irradiation of Th-232. This study quantitatively predicted the presence of Ac-228 in Ac-225 eluates under various conditions and showed how Ac-228 can be suppressed by introducing minimal postelution decay times.

The effectiveness and safety of Auger electron (AE)-emitting epidermal growth factor receptor (EGFR)-targeted panitumumab-197gHg-gold nanoparticles (AuNPs) or nontargeted 197gHg-AuNPs for treating glioblastoma multiforme (GBM) were studied after convection-enhanced delivery (CED) in NOD-Rag1nullIL2rgnull (NRG) mice with orthotopic GBM tumors. We hypothesized that EGFR binding, internalization, and nuclear importation of panitumumab-197gHg-AuNPs would make these radiation nanomedicines more effective than nontargeted 197gHg-AuNPs because of the subcellular range of AEs, but that both would be safe because of their confined localization at the infusion site in the brain after CED. Methods: Localization of 197gHg in NRG mice after CED was assessed by SPECT/CT imaging. Toxicity was evaluated after CED of 1.8 × 1011 to 2.3 × 1011 panitumumab-197gHg-AuNPs (0.9 ± 0.5 MBq) or nontargeted 197gHg-AuNPs (2.6 ± 0.8 MBq) by hematology, blood biochemistry, and body weight monitoring. Mice with U251-Luc tumors were treated with panitumumab-197gHg-AuNPs (1.3 ± 0.3 MBq) or 197gHg-AuNPs (1.1 ± 0.4 MBq), panitumumab-AuNPs or AuNPs, or 0.9% NaCl. Tumor response was assessed by MRI and Kaplan-Meier median survival. Self-absorbed doses in the nucleus of tumor cells from AEs were estimated. Toxicity to the brain was assessed by MRI and ex vivo histologic examination. Results: Both panitumumab-197gHg-AuNPs and 197gHg-AuNPs were confined to the infusion site with no redistribution to healthy brain or other organs. There was no hematologic, liver, or kidney toxicity and no decrease in body weight. MRI at 21 d and 34 d revealed that tumors in mice treated with panitumumab-197gHg-AuNPs or 197gHg-AuNPs were significantly smaller than tumors in mice treated with panitumumab-AuNPs, AuNPs, or 0.9% NaCl. Median survival in mice treated with panitumumab-197gHg-AuNPs (59 d) was significantly longer than that in mice treated with nontargeted 197gHg-AuNPs (43 d) or control treatments (31-33 d). The self-radiation absorbed dose in the nucleus of GBM tumor cells from AEs was 3.2-fold higher for panitumumab-197gHg-AuNPs (40.2 Gy) than for 197gHg-AuNPs (12.2 Gy). Conclusion: EGFR-targeted panitumumab-197gHg-AuNPs were more effective than nontargeted 197gHg-AuNPs for treating U251-Luc human GBM tumors in NRG mice. This approach may offer a safe and effective treatment for GBM that could improve patient survival.

Objective.High-energy proton irradiation of232Th produces both225Ac and its precursor225Ra, the latter being underexplored despite its potential applicability at relevant facilities. This study aims to provide a theoretical basis for232Th-based225Ra production by modeling the associated yields and radioisotopic impurity levels.Approach.Production yields of225Ra and levels of228Ra impurity were calculated using Monte Carlo simulations for proton energies of 100-800 MeV, total232Th target thicknesses of 0.125-8 mm, and an irradiation time of 15 d. A theoretical model was developed for predicting the cumulative yield of225Ac eluates from a225Ra yield. The levels of228Ra-derived228Ac impurity in225Ac eluates and the postelution decay times required to suppress228Ac to acceptable thresholds were modeled and computed.Main results.The calculated225Ra yields at the end of bombardment for a 15 d irradiation ranged from 2.3 ± 0.3 MBq µA-1at 100 MeV to 563.1 ± 12.3 MBq µA-1at 700 MeV. Increases in225Ra yield were most pronounced when the proton energy was raised from 100 to 200 MeV, with diminishing returns at higher energies. The cumulative yield of225Ac eluates was about 29.1% of a225Ra yield under combined conditions of hypothetical and empirical settings. Postelution times of at least 25.1-30.1 h should be allowed to reduce228Ac impurity levels to below 0.1%.Significance.The developed models provide a quantitative basis for evaluating and optimizing225Ra production via proton irradiation of232Th. This study quantitatively predicted the presence of228Ac in225Ac eluates under various conditions and showed how228Ac can be suppressed by introducing minimal postelution decay times.

197gHg and 197mHg are attractive radionuclides for radioimmunotherapy of cancer due to their abundant Auger electron emissions (23.2 and 19.4 electrons/decay, respectively). Our aim was to study the cytotoxicity and DNA-damaging properties of panitumumab labeled with 197gHg/197mHg on a panel of human breast cancer cells expressing different levels of epidermal growth factor receptor (EGFR) (104 to 106 EGFR/cell) and evaluate the tumour and normal tissue uptake of these radioimmunoconjugates in mice with EGFR-overexpressing MDA-MB-468 human breast cancer xenografts (106 EGFR/cell). Panitumumab was conjugated to 2-[4,7,10-tris(2-amino-2-oxoethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetamide (TCMC) or a sulphur-rich (NS4) bifunctional chelator to complex 197gHg/197mHg or directly labeled with 197gHg/197mHg through endogenous mercury binding sites. All radioimmunoconjugates bound specifically (87–91

Mercury-197m (197mHg, t1/2 = 23.8 h) and mercury-197g (197gHg, t1/2 = 64.14 h) possess favorable nuclear properties for imaging and targeted therapy, but the development of suitable chelators for mercury-based radiopharmaceuticals remains underexplored. Additionally, accurate imaging and quantification of mercury isotopes, particularly in dual-isotope formats, require tools that account for their complex decay schemes. Phantom imaging studies are essential for validating spatial resolution, quantitative accuracy, and isotope-specific calibration prior to in vivo application. In this study, we investigated the commercially available ligand H4Tetrathiol for chelation of [197m/gHg]Hg2+ and developed a robust imaging and quantification pipeline to support the use of these nuclear isomers in preclinical imaging. Radiolabeling of H4Tetrathiol yielded exceptionally efficient complexation, achieving the lowest ligand-to-metal ratio reported for radio-mercury. The resulting [197m/gHg]Hg2+-complex demonstrated high in vitro stability in the presence of serum proteins, glutathione, and competing biologically relevant metal ions, though it exhibited kinetic lability when challenged with excess HgCl₂. In vivo biodistribution studies in mice showed a distinct pharmacokinetic profile from unchelated [197m/gHg]HgCl₂, suggesting in vivo complex stability. Phantom imaging studies with a high sensitivity collimator demonstrated submillimeter resolution (≥ 1.1 mm) for both 197gHg and 197mHg, with decay behavior consistent with known half-lives. To facilitate accurate quantification, we developed HgQuant, a Python-based tool for isotope-specific calibration, Bateman decay correction, and automated dual-isotope analysis. This tool enabled reproducible, time-resolved quantification in both phantom and in vivo settings. These results establish Tetrathiol as a promising scaffold for mercury-based theranostics, offering efficient radiolabeling and in vivo stability. The integration of high-resolution imaging and HgQuant-based quantification of each isomer establishes a comprehensive framework for advancing [197m/gHg]Hg radiopharmaceutical development.

Introduction: Radiolanthanides 132La and 135La form a promising chemically matched theranostic pair. With a half-life of 18.95 h, 135La acts as the therapeutic isotope as it releases approximately 11 Auger electrons per decay, making it compatible with targeted Auger electron therapy (TAET), whereas 132La with half-life of 4.58 h undergoes positron emission making it compatible with imaging via positron emission tomography (PET). Methods: 132/135La were produced via irradiation of natural barium targets (99.9 %) with 12.8 MeV protons. A two-step separation scheme using extraction chromatographic resin TK200 (50-100 mu m) and cation exchange resin Dowex 50Wx4 (200-400 mesh) was designed. Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify non-radioactive impurities in each fraction of the separation method. The distribution coefficients of La3+ in HNO3 on the TK200 resin and on both Dowex 50Wx8 (200-400 mesh) and Dowex 50Wx4 resins in ammonium alpha-hydroxyisobutyrate (pH 4.8) were determined, respectively. Results: This novel separation scheme allowed for reliable separation of [132/135La]La3+ from the Ba2+ target material, resulting in a high radiochemical yield of 98.3 +/- 2.1 % (n = 3) with the final elute being directly compatible with subsequent radiolabeling due to the use of ammonium alpha-hydroxyisobutyrate to eliminate steps in the radiopharmaceutical synthetic process.

We describe here radiation nanomedicines for glioblastoma multiforme (GBM) composed of gold nanoparticles (AuNPs) that integrate the Auger electron-emitter, 197Hg. [197Hg]Hg-AuNPs were conjugated to anti-epidermal growth factor receptor (EGFR) panitumumab or were non-targeted. Our aim was to compare the cytotoxicity and DNA-damaging properties in vitro of panitumumab-[197Hg]Hg-AuNPs and non-targeted [197Hg]Hg-AuNPs on U251-Luc human GBM cells and estimate their cellular dosimetry. We further aimed to compare the biodistribution in vivo of panitumumab-[197Hg]Hg-AuNPs and [197Hg]Hg-AuNPs after convection-enhanced delivery (CED) in NRG mice with U251-Luc tumours in the brain and estimate the absorbed doses in the tumour and surrounding margins of healthy brain. [197Hg]Hg-AuNPs (26.8 ± 6.4 nm) were produced with a radiochemical yield of 98 ± 1

Objective. Conventional232Th target thicknesses used for225Ac production are substantially smaller than the proton ranges, underutilizing the225Ac production potential of proton beams. This study explores theoretical optimal thicknesses of232Th targets at widely used proton energies, 70-200 MeV.Approach. Yields of225Ac and impurity levels of227Ac were calculated for proton energies of 70-200 MeV and232Th target thicknesses of 0.05-24 mm using Monte Carlo simulations. Ranges of optimal target thicknesses were defined for each proton energy based on the relative rates of change (RROCs) of225Ac yields per target thickness of 0.25 mm and on energy-adjusted RROC thresholds. Expected225Ac yield gains from using the optimal thicknesses were also estimated.Main results. The ranges of theoretical optimal thicknesses for representative energies, 70, 100, 160, and 200 MeV, were found to be 2-2.25 mm, 4.5-6.25 mm, 7.75-14.5 mm, and 14.25-21.75 mm, respectively. All these thicknesses are markedly larger than those of the conventional thin targets used for medium- to large-scale225Ac production, 0.25 mm and 0.5 mm. By using these optimal target thicknesses,225Ac yields are expected to increase by factors of up to 8.8 at 70 MeV and 63.8 at 200 MeV. Actinium-227 impurity levels were unaffected by target thickness optimization at all proton energies.Significance. Optimizing232Th target thicknesses can provide proton accelerator facilities operating in the 70-200 MeV range with a straightforward means of increasing their225Ac production capacity. Optimal target thicknesses offer greater225Ac yield scalability at higher energies near 200 MeV, while enabling large-scale225Ac production at lower energies close to 70 MeV.

Targeted Alpha Therapy (TAT) holds significant promise as a localized treatment for cancer. Encouraging clinical results from using peptides and antibodies labeled with alpha emitters to treat patients with metastatic cancers, particularly those who have not responded to other therapies, provide compelling evidence of TAT's potential. To fully realize the benefits of TAT, it is essential to carefully select appropriate radionuclides and targeting delivery systems to maximize therapeutic efficacy while minimizing nonspecific toxicity to healthy tissues. This review explores key radiochemical, radiopharmaceutical, and radiation-biological considerations for current TAT candidates, and proposes additional potential candidates, establishing a foundation and criteria for the ongoing development of TAT radiopharmaceuticals.

The use of chemically matched theranostic radiometals in nuclear medicine presents a paradigm shift in personalized medicine with immense potential to treat advanced cancers. The nuclear isomers, mercury-197g (197gHg, half-life 64.14 h) and mercury-197m (197mHg, half-life 23.8 h) possess optimal physical decay properties to be applied in theranostic radiopharmaceuticals; however, their use has been limited due to the lack of suitable bifunctional chelators (BFCs) capable of attaching the radionuclides to disease targeting biomolecules. Herein we report the development and evaluation of two novel 197m/gHg BFCs derived from a 15-membered thiacrown ether macrocycle (NS4) bearing isothiocyanate (-NCS) or tetrazine (-Tz) bifunctional handles to allow conjugation to biomolecules. Both chelators were synthesized and radiolabeled with 197m/gHg, assessed for complex stability, and bioconjugation to trastuzumab (TmAb), a monoclonal antibody targeting HER2 receptors. NS4-Tz efficiently and stably complexes [197m/gHg]Hg2+ and exhibited excellent in vitro stability in both glutathione and human serum. In contrast, NS4-NCS showed lower radiometal incorporation yields and reduced complex stability, likely attributed to non-specific interactions of the isothiocyanate group with Hg2+. NS4-Tz was successfully conjugated to transcyclooctene-modified TmAb with favourable chelator-to-antibody ratios and subsequently radiolabeled. Due to non-specific Hg2+ binding to TmAb observed during direct labeling, a two-step labeling strategy was employed to improve selectivity. The resulting [197m/gHg]Hg-NS4-Tz-TmAb construct demonstrated specific binding to HER2-positive SK-BR-3 cells in vitro and, in the first in vivo study of a [197m/gHg]Hg-labeled immunoconjugate, confirmed tumour-specific uptake in a SKOV-3 xenograft mouse model. Biodistribution and SPECT/CT studies of the BFC complex alone, [197m/gHg]Hg-NS4-Tz, revealed high hepatic and splenic accumulation, with some renal uptake possibly due to transchelation or tracer pharmacokinetics. While long-term in vivo stability of the radioimmunoconjugate remains a challenge, NS4-Tz shows significant promise for applications with faster-clearing vectors such as peptides or small molecules. Future work will focus on improving hydrophilicity and further optimizing chelator design for mercury-based theranostics.

Antimony-119 (119Sb, t1/2 = 38.19 h) is an Auger electron emitting radionuclide of interest for radiopharmaceutical therapy (RPT). The potential of 119Sb has only been explored theoretically, due to the absence of a suitable bifunctional chelator that enables the attachment of the radionuclide onto a radiopharmaceutical. Meanwhile, potential chelators are difficult to evaluate given that the production and radiochemical purification of 119Sb has not been optimized for radiopharmaceutical applications. 119Sb can be produced from proton bombardment of tin-119 (119Sn) targets on medical cyclotrons, subsequently the nanograms of radioantimony must be efficiently separated from the macroscopic (> mg) amount of target material while being recovered in a matrix suitable for chelation. To this end, a solid phase extraction (SPE) method employing a novel dibutyl ether (DBE) resin was developed to separate radioantimony from tin targets. The DBE resin was synthesized and characterized using thermogravimetric analysis, total organic carbon, and 1H nuclear magnetic resonance spectroscopy. The DBE resin exhibited excellent capacity (>8 mg Sb per gram) and integrity. Distribution coefficients (KD) for Sb(V) (KD up to 4600) and Sn(IV) (KD <0.3) showed good separation (Separation factor of >15,000) of both elements at high concentrations of HCl. Finally, dynamic separations with the DBE resin were capable of recovering up to 79 ± 2 % of radioantimony (1xxSb(III)) in 2 mL of 0.5 M sodium thioglycolate solution when separating nanogram quantities of 1xxSb from tens of milligrams of stable tin. Quantitative recovery of Sn was also achieved in just 1.5 mL of concentrated hydrochloric acid, indicating the potential for target recycling of enriched 119Sn required for pre-clinical evaluation of 119Sb.

Targeted Alpha Therapy has shown great promise in cancer treatment, sparking significant interest over recent decades. However, its broad adoption has been impeded by the scarcity of alpha-emitters and the complexities related to their use. The availability of these radionuclides is often constrained by the intricate production processes and purification, as well as regulatory and logistical challenges. Moreover, the high cost and technical difficulties associated with handling and applying alpha-emitting radionuclides pose additional barriers to their clinical implementation.This Alpha Atlas provides an in-depth overview of the leading alpha-particle emitting radionuclide candidates for clinical use, focusing on their production processes and supply chains. By mapping the current facilities that produce and supply these radionuclides, this atlas aims to assist researchers, clinicians, and industries in initiating or scaling up the applications of alpha-emitters. The Alpha Atlas aspires to act as a strategic guide, facilitating collaboration and driving forward the integration of these potent therapeutic agents into cancer treatment practices.

In this work, we introduce the cyclen-based metal chelator DOTThia comprising four methylthiazole arms for metal complexation. Together with the recently described congener DOTI-Me bearing four methylimidazole arms, the radiochemistry of these two compounds with 212Pb, 213Bi, and 225Ac was investigated thoroughly. Radiolabeling experiments were performed at various pH values and temperatures to determine the optimal conditions for quantitative radiochemical conversions. Experiments revealed excellent complexation properties of DOTThia for 212Pb at room temperature, comparable to those of the current gold standard for Pb complexation, TCMC, while it was not well suited for 213Bi. Contrarily, DOTI-Me exhibited quantitative radiochemical conversions for 213Bi at pH 5.5 and room temperature, outperforming the metal chelator macropa, but was not able to quantitatively complex 212Pb under any conditions investigated. Of note, both novel chelators were not able to bind 225Ac. In preliminary experiments, we could also show that a functionalized DOTI-Me derivative is capable of complexing 213Bi selectively from 225Ac solutions. This feature may allow the preparation of 213Bi-labeled radiotracers directly from 225Ac solutions without the need for an 225Ac/213Bi generator. However, more detailed studies are needed to fully explore this potential application. Altogether, our results support the future development of 212Pb-labeled radiopharmaceuticals using bifunctional derivatives of DOTThia as well as of 213Bi-labeled radiotracers based on the DOTI-Me scaffold.

Antimony-119 (119Sb, t1/2 = 38.19 h) is an Auger electron emitting radionuclide of interest for radiopharmaceutical therapy. It can be directly produced by proton bombardment of tin-119 using low energy cyclotrons. The radiochemical separation methods available for recovering 119Sb from the bulk Sn target material are lacking, particularly with respect to matrix suitability for further applications. Eight new resins were successfully synthesized, evaluating combinations of two different resin support materials with three different chain lengths of ethers (dibutyl, dipentyl, dioctyl) as well as fluorinated alcohol as the impregnated extractant. All resins showed good stability, losing less than 1

Introduction: Auger electron-emitting radionuclides with low (0.001-1 keV) energy, short-range (2-500 nm), and high linear energy transfer (4-26 keV/mu m) can play an important role in the targeted radionuclide therapy (TRT) of cancer. Er-165 is a pure Auger electron-emitting radionuclide, making it a useful tool for the fundamental studies of the biological effects of Auger electrons. This work develops a simple, inexpensive, high separation factor, and high molar activity radiochemical isolation process for the production of Er-165 (t(1/2) 10.36 h) suitable for TRT in vitro and in vivo studies using irradiated Ho-nat solid targets. Methods: Small medical cyclotron proton-irradiation of Ho-nat targets produced Er-165 in GBq scale quantities. Er-165 was isolated using cation exchange chromatographic resin (AG 50W-X8, 200-400 mesh, 20 mL, under atmospheric pressure) using alpha-hydroxyisobutyric acid (70 mM, pH 4.75) followed by extraction using TK212, TK211, and TK221 extraction chromatographic columns. Radio nuclidic and chemical purity of the final Er-165 were confirmed using HPGe Gamma spectrometry and induction coupled plasma-mass spectrometry analysis, respectively. The purified Er-165 was radiolabeled with two radiometal chelators (DOTA and Crown) and used to produce a new Auger electron-emitting radiopharmaceutical, [Er-165]Er-Crown-TATE. Results: Irradiation of 200 mg Ho-nat targets with 20-30 mu A of 12.8 MeV protons produced Er-165 at 25 +/- 5 MBqmu A(-1)h(-1). The 4.5 +/- 0.5 h radiochemical isolation yielded GBq scale of Er-165 in 0.05 M HCl (2 mL) with a radiochemical yield of 78.0 +/- 5.6% decay corrected to the end of bombardment (EoB) and a Ho/Er-165 separation factor of (1.14 +/- 0.25) x 10(6). The product showed high radio nuclidic purity and chemical purity. Concentration-dependent radiolabeling experiments with Crown and DOTA were performed resulting in the successful labeling of Er-165 with high (>90%) radiochemical yield. Radiolabeling experiments with Crown-TATE were performed 8 h after EoB and synthesized [Er-165]Er-Crown-TATE at molar activities of 202.4 MBqnmol(-1) at the end of synthesis (EoS). Conclusions: A 3 h cyclotron irradiation and 4.5 h radiochemical separation produced GBq-scale Er-165 suitable for producing radiopharmaceuticals at molar activities satisfactory for investigations of targeted radionuclide therapeutic effects of Auger electron emissions. This will enable future fundamental radiation biology experiments of pure Auger electron-emitting therapeutic radiopharmaceuticals, such as [Er-165]Er-Crown-TATE, which will be used to understand the impact of Auger electrons in TRT

The focus of this chapter is to provide the various production routes for radionuclides that have potential therapeutic qualities. Given the need for diagnostic pairing for many therapeutic radionuclides, production routes for several photo-emitting counterparts are also discussed. The goal of this chapter is to provide a summary of the physical, chemical and purity qualities including radiochemical, radionuclidic and specific/molar activities, for the proposed theranostic pairs, recognizing that in many cases compromises will have to be made. As of 2023, the vast majority of global diagnostic imaging is performed with 18F, 68Ga and 99mTc, all of which can be produced by cyclotrons or generators. There is no general approach to producing radionuclides for therapy. However, since most of these radionuclides are neutron-rich they are generally produced by neutron capture, fission, (ɣ,n) or via charged particle spallation of targets distant from the desired product. In the latter case, there will generally be a number of undesired radionuclidic impurities. Often these impurities cannot be removed through chemistry. The purification of mixed products has been achieved by passing the mixture through an on-line or off-line isotope separator. Details for these approaches will be considered.