Large scale accelerator production of 225Ac: Effective cross sections for 78–192 MeV protons incident on 232Th targets

Griswold, Justin; Medvedev, Dmitri; Engle, Jonathan W.; Copping, Roy; Fitzsimmons, Jonathan; Radchenko, Valery; Cooley, J. C.; Fassbender, Michael E.; Denton, David; Murphy, Karen E.; Owens, Allison; Birnbaum, Eva R.; John, Kevin D.; Nortier, F.M.; Stracener, D. W.; Heilbronn, L.; Mausner, L.F.; Mirzadeh, Saed

doi:10.1016/j.apradiso.2016.09.026

Cited by 75 publications

(57 citation statements)

References 44 publications

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“…The current supply from this production route amounts to approximately 68 GBq per year [25]. Additional supply has recently become available from spallation of 232 Thorium with high energy protons [26]. Considering a typical dose of 8 MBq 225 Ac-PSMA-617 per treatment cycle, several thousand patient doses can thus be provided per year, allowing the further development of the therapy in large scale prospective clinical trials.…”

Section: Discussionmentioning

confidence: 99%

225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: a pilot study

Sathekge

Bruchertseifer

Knoesen

et al. 2018

Eur J Nucl Med Mol Imaging

274

235

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Ac-PSMA-617 RLT of chemotherapy-naïve patients with advanced metastatic prostate carcinoma led to a ≥ 90% decline in serum PSA in 82% of patients including 41% of patients with undetectable serum PSA who remained in remission 12 months after therapy. The remarkable therapeutic efficacy reported in this study could be achieved with reduced toxicity to salivary glands due to de-escalation of administered activities in subsequent treatment cycles. This necessitates further exploration for informing clinical practice and clinical trial design.

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Section: Discussionmentioning

confidence: 99%

225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: a pilot study

Sathekge

Bruchertseifer

Knoesen

et al. 2018

Eur J Nucl Med Mol Imaging

274

235

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“…Using this method, a 10-d irradiation campaign of a 5 g/cm 2 thorium target was able to produce curie levels of 225 Ac (19). The quality of the accelerator-produced 225 Ac was equal to that of the 229 Th generated; however, the impact of coproduced 227 Ac remains to be evaluated (19). 225 Ac (t ½ 5 10.0 d; 5.8-MeV a-particle) decays sequentially through 6 dominant daughters to stable 209 Bi ( Table 1).…”

Section: Atmentioning

confidence: 99%

“…Indirect mechanisms increasing α-particle lethal potency, including cross-fire effect (CF), radiation-induced bystander effect (RIBE), and abscopal effect (AbsE) (6). among Oak Ridge, Brookhaven, and Los Alamos National Laboratories recently produced millicurie quantities of 225 Ac by irradiating a natural thorium target at beam energies of between 78 and 192 MeV (19). Using this method, a 10-d irradiation campaign of a 5 g/cm 2 thorium target was able to produce curie levels of 225 Ac (19).…”

Section: Atmentioning

confidence: 99%

“…among Oak Ridge, Brookhaven, and Los Alamos National Laboratories recently produced millicurie quantities of 225 Ac by irradiating a natural thorium target at beam energies of between 78 and 192 MeV (19). Using this method, a 10-d irradiation campaign of a 5 g/cm 2 thorium target was able to produce curie levels of 225 Ac (19). The quality of the accelerator-produced 225 Ac was equal to that of the 229 Th generated; however, the impact of coproduced 227 Ac remains to be evaluated (19).…”

Section: Atmentioning

confidence: 99%

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α-Emitters for Radiotherapy: From Basic Radiochemistry to Clinical Studies—Part 1

et al. 2018

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Learning Objectives: On successful completion of this activity, participants should be able to (1) cite α-emitter families available for therapeutic use and understand their current production limit; (2) consider radiation safety concerns when handling α-emitters; and (3) overcome radiolabeling and daughter redistribution hurdles with the approaches described in this educational review. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, SAM, and other credit types, participants can access this activity through the SNMMI website (http://www.snmmilearningcenter.org) through June 2021.With a short particle range and high linear energy transfer, α-emitting radionuclides demonstrate high cell-killing efficiencies. Even with the existence of numerous radionuclides that decay by α-particle emission, only a few of these can reasonably be exploited for therapeutic purposes. Factors including radioisotope availability and physical characteristics (e.g., half-life) can limit their widespread dissemination. The first part of this review will explore the diversity, basic radiochemistry, restrictions, and hurdles of α-emitters. Radi onuclide strategies for curative therapy, disease control, or palliation are positioned to constitute a major portion of nuclear medicine. The range of available therapeutic radioisotopes, including a, b, or Auger electron emission, has considerably expanded over the last century (1). Matching the particle decay pathway, effective range, and relative biological effectiveness to tumor mass, size, radiosensitivity, and heterogeneity is the primary consideration for maximizing therapeutic efficacy. b-emitting radioisotopes have the longest particle pathlength (#12 mm) and lowest linear energy transfer (LET) (;0.2 keV/mm), supporting their effectiveness in medium to large tumors (Fig. 1). Although the long b-particle range is advantageous in evenly distributing radiation dose in heterogeneous tumors, it can also result in the irradiation of healthy tissue surrounding the tumor site. Conversely, Auger electrons have high LET (4-26 keV/mm) but a limited pathlength of 2-500 nm that restricts their efficacy to single cells, thus requiring the radionuclide to cross the cell membrane and reach the nucleus. Finally, a-particles have a moderate pathlength (50-100 mm) and high LET (80 keV/mm) that render them especially suitable for small neoplasms or micrometastases. A recent clinical study highlighted the ability of a-radiotherapy to overcome treatment resistance to b-particle therapy, prompting a paradigm shift in the approach toward radionuclide therapy (2).For optimized therapeutic efficacy, the a-cytotoxic payload is expected to accumulate selectively in diseased tissue and deliver a suf...

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“…225 Ac is produced via decay of 233 U or from the neutron transmutation of 226 Ra to 225 Ac [21] at the US Department of Energy, Oak Ridge National Laboratory, and the Institute for Transuranium Elements in Karlsruhe, Germany. It has also been produced through a high-energy proton accelerator: 227 Th(p,x) 225 Ac at Los Alamos National Laboratory [33]. However, production via radioactive decay and neutron irradiation methods lack the capacity to enable clinical use of 225 Ac-radiolabelled peptides.…”

Section: Characteristics Of Therapeutic Alpha Radionuclidesmentioning

confidence: 99%

Targeted Alpha Particle Therapy for Neuroendocrine Tumours: The Next Generation of Peptide Receptor Radionuclide Therapy

Navalkissoor

Grossman

2018

Neuroendocrinology

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Neuroendocrine tumours (NETs) are being seen increasingly frequently, but to date only complete surgical resection is curative. However, among the various therapeutic options, peptide receptor radionuclide therapy, linking a radioactive moiety to an octreotide derivative, has been shown to be highly efficacious and a well-tolerated therapy, improving progression-free survival and probably overall survival. Nevertheless, the current radionuclides in use are beta particle emitters with non-optimal radiobiological properties. A new generation of alpha particle-emitting radionuclides is being developed, with advantages in terms of very high energy and a short path length, which should theoretically show higher efficacy. We survey the current developments in this field, emphasising the exciting potential of this novel form of therapy for NETs.

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Large scale accelerator production of 225Ac: Effective cross sections for 78–192 MeV protons incident on 232Th targets

Cited by 75 publications

References 44 publications

225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: a pilot study

225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: a pilot study

α-Emitters for Radiotherapy: From Basic Radiochemistry to Clinical Studies—Part 1

Targeted Alpha Particle Therapy for Neuroendocrine Tumours: The Next Generation of Peptide Receptor Radionuclide Therapy

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