Background <p>Recent EMA and FDA approvals of Lu-DOTATATE and Lu-PSMA-617 have led to increased demand for radiotherapeutic <InlineEquation ID="IEq9"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq9.gif" Format="GIF" Height="10" Rendition="HTML" Resolution="72" Type="Linedraw" Width="19" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{177}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mn>177</mn> </mmultiscripts> </math></EquationSource> </InlineEquation>Lu, due to its promising potential to treat castration-resistant neuroendocrine cancers. Conventional reactor production methods pose challenges related to cost, waste management, and local availability. In comparison, accelerators produce less waste, have lower maintenance costs, and can be directly integrated into hospital settings. In this study, we evaluate the production of radiotherapeutic <InlineEquation ID="IEq10"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq9.gif" Format="GIF" Height="10" Rendition="HTML" Resolution="72" Type="Linedraw" Width="19" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{177}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mn>177</mn> </mmultiscripts> </math></EquationSource> </InlineEquation>Lu using a 10 mA, 18 MeV <InlineEquation ID="IEq11"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq2.gif" Format="GIF" Height="16" Rendition="HTML" Resolution="72" Type="Linedraw" Width="25" /> </InlineMediaObject> <EquationSource Format="TEX">\(D^+\)</EquationSource> <EquationSource Format="MATHML"><math> <msup> <mi>D</mi> <mo>+</mo> </msup> </math></EquationSource> </InlineEquation> compact linear accelerator design. The design consists of a single radio-frequency quadrupole (RFQ) and seven drift tube linacs (DTLs) that achieve a beam efficiency of 98.5% over a total length of <InlineEquation ID="IEq12"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq12.gif" Format="GIF" Height="14" Rendition="HTML" Resolution="72" Type="Linedraw" Width="34" /> </InlineMediaObject> <EquationSource Format="TEX">\(12\,\text {m}\)</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mn>12</mn> <mspace width="0.166667em" /> <mtext>m</mtext> </mrow> </math></EquationSource> </InlineEquation>. Deuteron activations on a 99% enriched [<InlineEquation ID="IEq13"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq13.gif" Format="GIF" Height="10" Rendition="HTML" Resolution="72" Type="Linedraw" Width="19" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{176}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mn>176</mn> </mmultiscripts> </math></EquationSource> </InlineEquation>Yb]<InlineEquation ID="IEq14"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq4.gif" Format="GIF" Height="16" Rendition="HTML" Resolution="72" Type="Linedraw" Width="48" /> </InlineMediaObject> <EquationSource Format="TEX">\(\hbox {Yb}_2\hbox {O}_3\)</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <msub> <mtext>Yb</mtext> <mn>2</mn> </msub> <msub> <mtext>O</mtext> <mn>3</mn> </msub> </mrow> </math></EquationSource> </InlineEquation> target are estimated using experimental and simulated excitation functions.</p> Results <p>A circular target with a radius of 1&#xa0;cm and 0.36 mm thickness is selected to optimize the yield of <InlineEquation ID="IEq15"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq9.gif" Format="GIF" Height="10" Rendition="HTML" Resolution="72" Type="Linedraw" Width="19" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{177}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mn>177</mn> </mmultiscripts> </math></EquationSource> </InlineEquation>Lu while minimizing the production of undesirable radioisotopes, including <InlineEquation ID="IEq16"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq16.gif" Format="GIF" Height="12" Rendition="HTML" Resolution="72" Type="Linedraw" Width="46" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{174g+m}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mrow> <mn>174</mn> <mi>g</mi> <mo>+</mo> <mi>m</mi> </mrow> </mmultiscripts> </math></EquationSource> </InlineEquation>Lu and <InlineEquation ID="IEq17"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq17.gif" Format="GIF" Height="10" Rendition="HTML" Resolution="72" Type="Linedraw" Width="31" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{177m}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mrow> <mn>177</mn> <mi>m</mi> </mrow> </mmultiscripts> </math></EquationSource> </InlineEquation>Lu. Model calculations indicate that the accelerator design can produce 11.3 μg of <InlineEquation ID="IEq19"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq9.gif" Format="GIF" Height="10" Rendition="HTML" Resolution="72" Type="Linedraw" Width="19" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{177}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mn>177</mn> </mmultiscripts> </math></EquationSource> </InlineEquation>Lu per hour. A 5-day irradiation is expected to yield approximately 1.07 mg of <InlineEquation ID="IEq20"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq9.gif" Format="GIF" Height="10" Rendition="HTML" Resolution="72" Type="Linedraw" Width="19" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{177}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mn>177</mn> </mmultiscripts> </math></EquationSource> </InlineEquation>Lu (4.4 TBq), while a 12-day irradiation can produce up to 1.9 mg (7.8 TBq). Following a 2-day processing period, the specific activity of the 5-day irradiated sample is projected to approach 0.6 TBq/mg, with a radiopurity of approximately 99.8%. The minimal burn-up of the <InlineEquation ID="IEq21"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq4.gif" Format="GIF" Height="16" Rendition="HTML" Resolution="72" Type="Linedraw" Width="48" /> </InlineMediaObject> <EquationSource Format="TEX">\(\hbox {Yb}_2\hbox {O}_3\)</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <msub> <mtext>Yb</mtext> <mn>2</mn> </msub> <msub> <mtext>O</mtext> <mn>3</mn> </msub> </mrow> </math></EquationSource> </InlineEquation> target suggests it may be recycled and reused over multiple irradiations.</p> Conclusions <p>The study confirms the feasibility of accelerator-based <InlineEquation ID="IEq22"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq9.gif" Format="GIF" Height="10" Rendition="HTML" Resolution="72" Type="Linedraw" Width="19" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{177}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mn>177</mn> </mmultiscripts> </math></EquationSource> </InlineEquation>Lu production as an alternative to existing reactor-based methods. The 10 mA, 18 MeV <InlineEquation ID="IEq23"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq2.gif" Format="GIF" Height="16" Rendition="HTML" Resolution="72" Type="Linedraw" Width="25" /> </InlineMediaObject> <EquationSource Format="TEX">\(D^+\)</EquationSource> <EquationSource Format="MATHML"><math> <msup> <mi>D</mi> <mo>+</mo> </msup> </math></EquationSource> </InlineEquation> RFQ-DTL design achieves an exceptionally high <InlineEquation ID="IEq24"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="41181_2025_358_Article_IEq9.gif" Format="GIF" Height="10" Rendition="HTML" Resolution="72" Type="Linedraw" Width="19" /> </InlineMediaObject> <EquationSource Format="TEX">\(^{177}\)</EquationSource> <EquationSource Format="MATHML"><math> <mmultiscripts> <mrow /> <mrow /> <mn>177</mn> </mmultiscripts> </math></EquationSource> </InlineEquation>Lu radiopurity and a competitive overall yield, which can meet the dose requirements of thousands of patients.</p>

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Compact accelerator-based production of carrier-free 177Lu from 18 MeV \(D^+\) on [176Yb]\(\hbox {Yb}_2\hbox {O}_3\)

  • Austin A. Morris,
  • Tianhao Wei,
  • Zhi Wang,
  • Ying Xia,
  • Meiyun Han,
  • Yuanrong Lu

摘要

Background

Recent EMA and FDA approvals of Lu-DOTATATE and Lu-PSMA-617 have led to increased demand for radiotherapeutic \(^{177}\) 177 Lu, due to its promising potential to treat castration-resistant neuroendocrine cancers. Conventional reactor production methods pose challenges related to cost, waste management, and local availability. In comparison, accelerators produce less waste, have lower maintenance costs, and can be directly integrated into hospital settings. In this study, we evaluate the production of radiotherapeutic \(^{177}\) 177 Lu using a 10 mA, 18 MeV \(D^+\) D + compact linear accelerator design. The design consists of a single radio-frequency quadrupole (RFQ) and seven drift tube linacs (DTLs) that achieve a beam efficiency of 98.5% over a total length of \(12\,\text {m}\) 12 m . Deuteron activations on a 99% enriched [ \(^{176}\) 176 Yb] \(\hbox {Yb}_2\hbox {O}_3\) Yb 2 O 3 target are estimated using experimental and simulated excitation functions.

Results

A circular target with a radius of 1 cm and 0.36 mm thickness is selected to optimize the yield of \(^{177}\) 177 Lu while minimizing the production of undesirable radioisotopes, including \(^{174g+m}\) 174 g + m Lu and \(^{177m}\) 177 m Lu. Model calculations indicate that the accelerator design can produce 11.3 μg of \(^{177}\) 177 Lu per hour. A 5-day irradiation is expected to yield approximately 1.07 mg of \(^{177}\) 177 Lu (4.4 TBq), while a 12-day irradiation can produce up to 1.9 mg (7.8 TBq). Following a 2-day processing period, the specific activity of the 5-day irradiated sample is projected to approach 0.6 TBq/mg, with a radiopurity of approximately 99.8%. The minimal burn-up of the \(\hbox {Yb}_2\hbox {O}_3\) Yb 2 O 3 target suggests it may be recycled and reused over multiple irradiations.

Conclusions

The study confirms the feasibility of accelerator-based \(^{177}\) 177 Lu production as an alternative to existing reactor-based methods. The 10 mA, 18 MeV \(D^+\) D + RFQ-DTL design achieves an exceptionally high \(^{177}\) 177 Lu radiopurity and a competitive overall yield, which can meet the dose requirements of thousands of patients.