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Research ArticleSupplement

Therapeutic Radiometals Beyond 177Lu and 90Y: Production and Application of Promising α-Particle, β−-Particle, and Auger Electron Emitters

Cristina Müller, Nicholas P. van der Meulen, Martina Benešová and Roger Schibli
Journal of Nuclear Medicine September 2017, 58 (Supplement 2) 91S-96S; DOI: https://doi.org/10.2967/jnumed.116.186825
Cristina Müller
1Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institut, Villigen-PSA, Switzerland
2Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland; and
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Nicholas P. van der Meulen
1Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institut, Villigen-PSA, Switzerland
3Laboratory of Radiochemistry, Paul Scherrer Institut, Villigen-PSA, Switzerland
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Martina Benešová
1Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institut, Villigen-PSA, Switzerland
2Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland; and
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Roger Schibli
1Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institut, Villigen-PSA, Switzerland
2Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland; and
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Abstract

In recent years, new α-particle–, β−-particle–, and Auger electron–emitting radiometals—such as 67Cu, 47Sc, 166Ho, 161Tb, 149Tb, 212Pb/212Bi, 225Ac, and 213Bi—have been produced and evaluated (pre)clinically for therapeutic purposes. In this short review article, the most important routes of production of these radiometals are critically discussed, as are examples of their application in preclinical and clinical studies.

  • radiometals
  • α-particles
  • β−-particles
  • Auger electrons
  • radionuclide therapy

Radionuclide tumor therapy has been used successfully for the treatment of disseminated disease (1). However, clinical application of therapeutic radionuclides is often driven by the availability of radionuclides rather than appropriate decay characteristics for a given disease indication. 90Y and 177Lu are routinely used for targeted radionuclide therapy (1). 90Y decays with a shorter half-life (t1/2) than 177Lu.

The emission of high-energy β−-particles has been used for radionuclide therapy in combination with peptides (e.g., 90Y-DOTATOC) and antibodies (e.g., ibritumomab tiuxetan [Zevalin; Spectrum Pharmaceuticals, Inc.]) (1). 177Lu emits low-energy β−-particles as well as γ-radiation, useful for dosimetry (Table 1) (1). It has been used for peptide receptor–targeted radionuclide therapy (2) and in combination with small molecules, such as prostate-specific membrane antigen (PSMA) ligands (3). Because of the relatively long range of β−-particles in tissue, tumor cells that are not directly targeted may also be affected. This so-called “crossfire” effect renders β−-emitters more suited for the therapy of larger metastases (4).

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TABLE 1

Decay Characteristics, Production Routes, and Diagnostic Matches for Radiometals for Therapeutic Application

In contrast to the low linear energy transfer (LET; ∼0.2 keV/mm) of β−-particles, α-particles have a high LET (80–100 keV/μm) but a shorter tissue range (4). The promising potential of high-LET radionuclides was demonstrated recently using 223RaCl2 (Xofigo; Bayer), which revived interest in α-emitters (5). Auger electrons induce multiple ionizations (LET, 4–26 keV/μm) in the immediate vicinity of the decay site and, thus, are promising for the treatment of single cancer cells (4).

In the introduction of new radionuclides for therapy, several properties should be taken into consideration. For the treatment of disseminated disease, the emission of high-LET particles is of particular interest; the coemission of radiation (for PET or SPECT) that can be imaged or the existence of a readily available diagnostic match is clearly an advantage. Moreover, the chemical properties of the radiometal should allow stable coordination using standard chelators. The half-life of the radiometal should match the clinical indications and logistics. The method of production needs to be safe and affordable to allow continuous worldwide supply of the radionuclide at a high quality and in a sufficient quantity.

Here we discuss the therapeutic radionuclides 47Sc, 67Cu, 149Tb, 161Tb, 166Ho, 212Pb/212Bi, 225Ac, and 213Bi (Table 1), selected in accordance with the aforementioned criteria.

COPPER-67

67Cu is a low-energy β−-emitter with γ-ray emission, useful for SPECT (Table 1). Studies using reactors and accelerators to produce 67Cu have been performed (6). The 68Zn(p,2p)67Cu route of production (proton energy, >70 MeV) appears to be most attractive (7); however, besides the desired 67Cu, large quantities of 64Cu (t1/2, 12.7 h) and 67Ga (t1/2, 78.3 h) are coproduced. The described separation methods required sizable columns containing chelating resin for primary separation to recover trace amounts of 67Cu from gram quantities of Zn target material (6,7). At present, there is a shortage of 67Cu supply, mainly because of the lack of cyclotrons producing high-energy protons.

Chelation of copper nuclides with a variety of macrocycles, including 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,8,11-tetraazacyclotetradecane-N,N′,N″,N‴-tetraacetic acid (TETA), 1,4,7-triazacyclononane-N-glutaric acid-N′,N″-diacetic acid (NODAGA), and 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]benzoic acid (CPTA), as well as cross-bridged macrocycles (e.g., 1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-4,11-diacetic acid [CB-TE2A]) and cage-type chelates (e.g., 1,8-diamino-3,6,10,13,16,19-hexaazabicyclo[6,6,6]-eicosane [DiAmSar]) (8,9), has been reported. Generally, the chelation of copper with tetraaza-macrocycles results in low tumor-to-background ratios because of the transchelation of copper to proteins accumulating in the liver (8). However, Zimmermann et al. (10) and Grünberg et al. (11) reported the successful use of DOTA and CPTA chelators in preclinical studies performed with a 67Cu-labeled anti–L1-CAM antibody and F(ab′)2 fragments.

In a pilot study, 67Cu-labeled anti-MUC1 mucin antibody C595 was evaluated for targeting bladder cancer after intravesical administration into cystectomy specimens (12). A study was performed in non-Hodgkin lymphoma patients with 67Cu-labeled TETA–Lym-1 antibody at diagnostic quantities followed by 4 therapy cycles (13). This radioimmunotherapy was revealed to be safe and effective (14,15). In 6 patients with colorectal tumors, 67Cu-labeled CPTA-mAB35 used for imaging purposes before surgery revealed high tumor uptake and favorable tumor-to-blood ratios relative to the results obtained with 131I-labeled antibody (16). These promising clinical results and the relatively easy access to 64Cu as a diagnostic match warrant further efforts to fully assess the therapeutic potential of 67Cu.

SCANDIUM-47

47Sc has decay characteristics similar to those of 67Cu and also has with 44Sc its theranostic match for PET (Table 1) (17). 47Sc can be produced with neutrons via the 47Ti(n,p)47Sc (18,19) or 46Ca(n,γ)47Ca → 47Sc (19,20) nuclear reaction. The production of 47Ca via the 48Ca(γ,n)47Ca nuclear reaction with electron linear accelerators was also evaluated (21). The production of 47Sc via 48Ti(p,2n)47Sc was attempted, but too much of the long-lived 46Sc was coproduced (19). The calcium route is straightforward because easy separation and ingrowing product allow for repeated separations (generator principle) (20).

With regard to complex formation and stability, it was revealed that DOTA forms stable scandium complexes (22). Recently, more specific chelators for scandium, such as monophosphorus acid DOTA analogs and AAZTA, were developed (23,24). The therapeutic potential of 47Sc was demonstrated with a DOTA-folate conjugate; reduced tumor growth and increased average survival time in mice were observed (17). Moreover, high-quality SPECT images were obtained in mice that received 47Sc-DOTA-folate (17). On the basis of these data, 47Sc seems to have promise for clinical application.

HOLMIUM-166

166Ho, a high-energy β−-emitter similar to 188Re (Eβ− average, 763 keV; t1/2, 17.0 h), coemits γ-rays useful for SPECT (Table 1). 166Ho is most frequently produced via the 165Ho(n,γ)166Ho route in combination with poly–lactic acid microspheres for intraarterial radioembolization in patients with liver metastases (25). For this purpose, natHo is incorporated into microspheres and activated with neutrons (26). 166Ho-microspheres administered intraarterially accumulated about 6-fold more in the tumor than in normal liver tissue in rats (27). Toxicity studies revealed no clinically relevant side effects in pigs (28). A phase 1 trial of intraarterial radioembolization using 166Ho-labeled poly–lactic acid microspheres was designed for the treatment of patients with liver cancer (25). 166Ho-based microspheres are considered to be superior to 90Y-based glass or resin microspheres because of the low cost of production of 166Ho and the possibility of SPECT imaging preceding therapy (26,29). Moreover, because holmium is highly paramagnetic, it can be visualized using MRI (25).

Clinical studies were performed to determine the safety and efficacy of treatment of hepatocellular carcinoma with a percutaneously administered 166Ho-chitosan complex (30). The 166Ho-chitosan complex therapy was efficient in terms of response and survival, and toxicity was acceptable, especially in patients with smaller tumors (30).

166Ho can also be produced via the 164Dy(2n,γ)166Dy → 166Ho nuclear reaction, yielding a carrier-free product useful for labeling of biomolecules (31). Among several investigated chelators, DOTA was found to be favorable and the kinetics of distribution of 166Ho-DOTA were similar to those of 177Lu-DOTA (32). The clinical safety and efficacy of 166Ho-labeled macrocyclic tetraphosphonate-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic acid (DOTMP) were assessed for skeleton-targeted radiotherapy of breast cancer–related bone metastases (33). The median overall survival time was 39.9 mo, and 2 patients remained progression-free for more than 6 y (33). A multicenter dose escalation study demonstrated the potential of 166Ho-DOTMP for the treatment of multiple myeloma (34).

TERBIUM-161

161Tb has chemical and physical characteristics similar to those of 177Lu but coemits a substantial number of Auger electrons in addition to β−-particles (35,36). 161Tb can be produced at a high specific activity by irradiation of enriched 160Gd in a reactor with a high neutron flux via the 160Gd(n,γ)161Gd→161Tb nuclear reaction (35). The separation of 161Tb from the gadolinium target material was performed by cation-exchange chromatography with α-hydroxyisobutyric acid followed by concentration of the 161Tb solution (37), similar to the production of 177Lu. Müller et al. were the first to use 161Tb in a preclinical therapy setting, with tumor-bearing mice (37). An improved therapeutic effect of 161Tb compared with that of 177Lu was described in 2 independent preclinical studies (38–40). The coemitted Auger electrons appeared to be favorable for therapeutic purposes, but the clinical superiority of 161Tb over 177Lu remains to be assessed when a steady supply of 161Tb can be guaranteed.

TERBIUM-149

149Tb was first proposed for targeted α-therapy by Allen and Blagojevic (41). Unlike most α-emitters, it decays predominantly by the emission of a single low-energy α-particle, positrons, and γ-radiation (Fig. 1A) (42). Beyer et al. chose the Nd(12C,5n)149Dy→149Tb production route at the European Organization for Nuclear Research (42). Later, 149Tb was produced by proton-induced spallation of a tantalum target followed by an online isotope separation process (37,42,43). In this scenario, 149Tb had to be separated from isobars and pseudoisobars with a mass of 149 using cation-exchange chromatography (37,42,43).

FIGURE 1.
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FIGURE 1.

(A) Decay of 149Tb to stable 149Sm, 145Nd, and 141Pr. EC = electron capture. (B) Maximum-intensity projection (MIP) of PET/CT image of AR42J tumor–bearing mouse 2 h after injection of 149Tb-DOTANOC (7 MBq). Bl = urinary bladder; Ki = kidney; Tu = tumor. (Adapted with permission of (45).)

The first preclinical therapy study with 149Tb was performed in a mouse model of leukemia with 49Tb-labeled cyclohexane-DTPA–functionalized rituximab (43). This therapy resulted in the long-term survival of mice without evidence of recurrence 120 d after treatment, whereas untreated mice or mice treated with a high dose of rituximab reached endpoint criteria after 37 or 43 d, respectively (43). Müller et al. reported the potential of 149Tb-DOTA-folate to treat KB tumor–bearing mice (37,44). The same group also investigated the positron emission of 149Tb, potentially allowing PET simultaneously with α-therapy (Fig. 1B) (45).

LEAD-212 (AND BISMUTH 212)

The β−-emitter 212Pb has been proposed as an in vivo α-emitter generator because of its α-emitting daughter nuclide, 212Bi (Fig. 2). 203Pb was recently described as a diagnostic match that can be readily produced from natTl via the 203Tl(p,n)203Pb nuclear reaction (46). The supply of 212Pb is based on the availability of 228Th extracted from spent nuclear fuel. Because 228Th-based generators were affected by radiolytic damage, a generator based on 224Ra (t1/2, 3.66 d) was developed using 228Th (47). The elution of 212Pb from the 224Ra/212Pb generator requires several steps, including separation from the daughter nuclide, 212Bi (48).

FIGURE 2.
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FIGURE 2.

Decay of 212Pb to 212Bi and stable 208Pb.

212Pb can be coordinated using a DOTA chelator or S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraaza-1,4,7,10-tetra(2-carbamoylmethyl)cyclododecane (TCMC), a macrocyclic chelator specifically developed for the complexation of lead (48). 212Pb-labeled antibodies were investigated in several studies, including human epidermal growth factor 2 (HER2)–targeting trastuzumab in mouse models of peritoneal cancer or orthotopic models of prostate cancer (48). Two clinical studies performed in patients with HER2-positive cancer to determine the safety, distribution, and pharmacokinetics of 212Pb-TCMC-trastuzumab and to determine dosimetry in a dose-escalation study indicated good tolerance and no evidence of radiation-related toxicity (49,50).

ACTINIUM-225

The decay of 225Ac results in 6 daughters (221Fr, 217At, 213Bi, 213Po, 209Pb, and 209Bi) with several α- and β−-disintegrations (Fig. 3) (51). 213Bi has been investigated extensively for α-therapy in (pre)clinical studies (52). 225Ac can be obtained in limited quantities (∼37 GBq/y) by radiochemical separation from a 229Th source (53,54). It can also be produced via the 232Th(p,2p6n)225Ac (55,56), 226Ra(p,2n)225Ac (57), and 226Ra(γ,n)225Ra → 225Ac nuclear reactions (58). The separation of 225Ac from the 226Ra target material was performed using lanthanide extraction resin chromatography (53). For the separation of 225Ac from its target material, a cumbersome 5-column system was reported (54). Because any target material used is radioactive (and long-lived), additional safety precautions must be taken into consideration during production.

FIGURE 3.
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FIGURE 3.

Decay of 225Ac to 213Bi and stable 209Bi.

The use of 225Ac may be challenging because of its decay chain and the fact that the first disintegration leads to the destruction of the metal complex (because of the high recoil energy) and the subsequent mobilization of the daughter radionuclides—a feature shared by all α-particle–emitting radionuclides (59–61).

DOTA chelators have been used to conjugate 225Ac to antibodies and small molecules (62). The effectiveness of 225Ac-labeled antibodies (such as anti-CD33, anti-CD18, anti-HER2/neu, and anti-PSMA) was demonstrated in vitro against leukemia and lymphoma as well as breast, ovarian, and prostate cancer cells (63). The treatment of prostate tumor–bearing mice with the PSMA-specific antibody 225Ac-J591 improved survival time over that of mice receiving unlabeled J591 (63). Other preclinical studies demonstrated the successful treatment of AR42J tumor–bearing mice with 225Ac-DOTATOC (64) and dose-dependent antitumor effects after treatment with 225Ac-labeled trastuzumab in an intraperitoneal ovarian tumor mouse model (65).

A phase 1 study with the anti-CD33 antibody 225Ac-lintuzumab (HuM195) was performed in patients with relapsed/refractory acute myeloid leukemia (66). Across all dose levels, antileukemic activity was evident. No acute toxicity other than liver function abnormalities occurred (66). A multicenter phase 1 trial with 225Ac-lintuzumab in combination with low-dose cytarabine resulted in a remarkable response represented by bone marrow blast reduction in more than 50% of treated patients (67).

Recently, Kratochwil et al. reported on first-in-human PSMA-targeted α-therapy of metastatic prostate cancer with 225Ac-labeled PSMA-617 (Fig. 4) (68). Strong antitumor activity and good tolerability were observed when 225Ac-PSMA-617 was applied in 3 cycles at bimonthly intervals (69). The 6-mo follow-up revealed a better response in patients treated with 225Ac-PSMA-617 than in patients treated with 177Lu-PSMA-617; however, frequent and more severe xerostomia occurred (70). The impressive clinical results in highly challenging clinical situations demonstrated the effectiveness of the α-emitter (68).

FIGURE 4.
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FIGURE 4.

(A) 68Ga-PSMA-11 PET/CT scan of patient with pretherapeutic tumor spread. PSA = prostate-specific antigen. (B) Restaging 2 mo after third cycle of 225Ac-PSMA-617 (9–10 MBq). (C) Restaging 2 mo after single additional consolidation therapy (6 MBq). 177Lu-PSMA-617 was contraindicated because of diffuse red marrow infiltration. (Reproduced from (68).)

BISMUTH-213

213Bi is available from a 225Ac/213Bi generator (Table 1; Fig. 2). Successful α-therapy with 213Bi has been demonstrated in many preclinical studies and several clinical trials (52). Clinically, 213Bi-labeled substance P was used for local administration in patients with located gliomas (71). High retention of the activity at the target site and radiation-induced necrosis of tumors were observed, without relevant acute local or systemic toxicity (71). The application of 213Bi-DOTATOC resulted in long-lasting antitumor responses in all treated patients (72). Despite the short physical half-life, even systemic application of 213Bi-lintuzumab in 31 patients was effective and resulted in remissions in patients with acute myeloid leukemia (73).

CONCLUSION

Here we discussed several radionuclides with a high therapeutic potential because of their decay properties. For most of them, availability is limited and this factor affects cost negatively. Depending on demand from clinics, the cost can decrease if production takes place in the private sector. Future endeavors of physicists, radiochemists, and radiopharmacists should focus on the development of reliable and efficient production methods. The various physical decay properties, such as variable half-lives and the emission of high- and low-LET particles, could allow the application of the most appropriate radionuclide for a given cancerous disease. Given these features, systemic radionuclide therapy fits the concept of personalized medicine perfectly and, thus, is among the most modern therapeutic strategies to be pursued.

DISCLOSURE

No potential conflict of interest relevant to this article was reported.

  • © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

REFERENCES

  1. 1.↵
    1. Zukotynski K,
    2. Jadvar H,
    3. Capala J,
    4. Fahey F
    . Targeted radionuclide therapy: practical applications and future prospects. Biomark Cancer. 2016;8:35–38.
    OpenUrl
  2. 2.↵
    1. Kam BL,
    2. Teunissen JJ,
    3. Krenning EP,
    4. et al
    . Lutetium-labelled peptides for therapy of neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2012;39(suppl 1):S103–S112.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Kulkarni HR,
    2. Singh A,
    3. Schuchardt C,
    4. et al
    . PSMA-based radioligand therapy for metastatic castration-resistant prostate cancer: the Bad Berka experience since 2013. J Nucl Med. 2016;57(suppl):97S–104S.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Kassis AI
    . Therapeutic radionuclides: biophysical and radiobiologic principles. Semin Nucl Med. 2008;38:358–366.
    OpenUrlCrossRefPubMed
  5. 5.↵
    1. Wissing MD,
    2. van Leeuwen FW,
    3. van der Pluijm G,
    4. Gelderblom H
    . Radium-223 chloride: extending life in prostate cancer patients by treating bone metastases. Clin Cancer Res. 2013;19:5822–5827.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Smith NA,
    2. Bowers DL,
    3. Ehst DA
    . The production, separation, and use of 67Cu for radioimmunotherapy: a review. Appl Radiat Isot. 2012;70:2377–2383.
    OpenUrlPubMed
  7. 7.↵
    1. Mausner LF,
    2. Kolsky KL,
    3. Joshi V,
    4. Srivastava SC
    . Radionuclide development at BNL for nuclear medicine therapy. Appl Radiat Isot. 1998;49:285–294.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Wadas TJ,
    2. Wong EH,
    3. Weisman GR,
    4. Anderson CJ
    . Copper chelation chemistry and its role in copper radiopharmaceuticals. Curr Pharm Des. 2007;13:3–16.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Anderson CJ,
    2. Wadas TJ,
    3. Wong EH,
    4. Weisman GR
    . Cross-bridged macrocyclic chelators for stable complexation of copper radionuclides for PET imaging. Q J Nucl Med Mol Imaging. 2008;52:185–192.
    OpenUrlPubMed
  10. 10.↵
    1. Zimmermann K,
    2. Grünberg J,
    3. Honer M,
    4. Ametamey S,
    5. Schubiger PA,
    6. Novak-Hofer I
    . Targeting of renal carcinoma with 67/64Cu-labeled anti-L1-CAM antibody chCE7: selection of copper ligands and PET imaging. Nucl Med Biol. 2003;30:417–427.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Grünberg J,
    2. Novak-Hofer I,
    3. Honer M,
    4. et al
    . In vivo evaluation of 177Lu- and 67/64Cu-labeled recombinant fragments of antibody chCE7 for radioimmunotherapy and PET imaging of L1-CAM-positive tumors. Clin Cancer Res. 2005;11:5112–5120.
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    1. Hughes OD,
    2. Bishop MC,
    3. Perkins AC,
    4. et al
    . Preclinical evaluation of copper-67 labelled anti-MUC1 mucin antibody C595 for therapeutic use in bladder cancer. Eur J Nucl Med. 1997;24:439–443.
    OpenUrlPubMed
  13. 13.↵
    1. Denardo GL,
    2. Denardo SJ,
    3. Kukis DL,
    4. et al
    . Maximum tolerated dose of 67Cu-2IT-BAT-LYM-1 for fractionated radioimmunotherapy of non-Hodgkin’s lymphoma: a pilot study. Anticancer Res. 1998;18:2779–2788.
    OpenUrlPubMed
  14. 14.↵
    1. DeNardo GL,
    2. Kukis DL,
    3. Shen S,
    4. DeNardo DA,
    5. Meares CF,
    6. DeNardo SJ
    . 67Cu- versus 131I-labeled Lym-1 antibody: comparative pharmacokinetics and dosimetry in patients with non-Hodgkin’s lymphoma. Clin Cancer Res. 1999;5:533–541.
    OpenUrlAbstract/FREE Full Text
  15. 15.↵
    1. O’Donnell RT,
    2. DeNardo GL,
    3. Kukis DL,
    4. et al
    . A clinical trial of radioimmunotherapy with 67Cu-2IT-BAT-Lym-1 for non-Hodgkin’s lymphoma. J Nucl Med. 1999;40:2014–2020.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    1. Delaloye AB,
    2. Delaloye B,
    3. Buchegger F,
    4. et al
    . Comparison of copper-67- and iodine-125-labeled anti-CEA monoclonal antibody biodistribution in patients with colorectal tumors. J Nucl Med. 1997;38:847–853.
    OpenUrlAbstract/FREE Full Text
  17. 17.↵
    1. Müller C,
    2. Bunka M,
    3. Haller S,
    4. et al
    . Promising prospects for 44Sc-/47Sc-based theragnostics: application of 47Sc for radionuclide tumor therapy in mice. J Nucl Med. 2014;55:1658–1664.
    OpenUrlAbstract/FREE Full Text
  18. 18.↵
    1. Bartos B,
    2. Majkowska A,
    3. Kasperek A,
    4. Krajewski S,
    5. Bilewicz A
    . New separation method of no-carrier-added 47Sc from titanium targets. Radiochim Acta. 2012;100:457–461.
    OpenUrlCrossRef
  19. 19.↵
    1. Srivastava SC
    . Paving the way to personalized medicine: production of some promising theragnostic radionuclides at Brookhaven National Laboratory. Semin Nucl Med. 2012;42:151–163.
    OpenUrlCrossRefPubMed
  20. 20.↵
    1. Müller C,
    2. Bunka M,
    3. Reber J,
    4. et al
    . Promises of cyclotron-produced 44Sc as a diagnostic match for trivalent β−-emitters: in vitro and in vivo study of a 44Sc-DOTA-folate conjugate. J Nucl Med. 2013;54:2168–2174.
    OpenUrlAbstract/FREE Full Text
  21. 21.↵
    1. Rane S,
    2. Harris JT,
    3. Starovoitova VN
    . 47Ca production for 47Ca/47Sc generator system using electron linacs. Appl Radiat Isot. 2015;97:188–192.
    OpenUrl
  22. 22.↵
    1. Price TW,
    2. Greenman J,
    3. Stasiuk GJ
    . Current advances in ligand design for inorganic positron emission tomography tracers 68Ga, 64Cu, 89Zr and 44Sc. Dalton Trans. 2016;45:15702–15724.
    OpenUrl
  23. 23.↵
    1. Kerdjoudj R,
    2. Pniok M,
    3. Alliot C,
    4. et al
    . Scandium(III) complexes of monophosphorus acid DOTA analogues: a thermodynamic and radiolabelling study with 44Sc from cyclotron and from a 44Ti/44Sc generator. Dalton Trans. 2016;45:1398–1409.
    OpenUrl
  24. 24.↵
    1. Nagy G,
    2. Szikra D,
    3. Trencsényi G,
    4. et al
    . AAZTA: an ideal chelating agent for the development of 44Sc PET imaging agents. Angew Chem Int Ed Engl. 2017;56:2118–2122.
    OpenUrl
  25. 25.↵
    1. Smits ML,
    2. Nijsen JF,
    3. van den Bosch MA,
    4. et al
    . Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial. J Exp Clin Cancer Res. 2010;29:70.
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Nijsen JF,
    2. Zonnenberg BA,
    3. Woittiez JR,
    4. et al
    . Holmium-166 poly lactic acid microspheres applicable for intra-arterial radionuclide therapy of hepatic malignancies: effects of preparation and neutron activation techniques. Eur J Nucl Med. 1999;26:699–704.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Nijsen F,
    2. Rook D,
    3. Brandt C,
    4. et al
    . Targeting of liver tumour in rats by selective delivery of holmium-166 loaded microspheres: a biodistribution study. Eur J Nucl Med. 2001;28:743–749.
    OpenUrlCrossRefPubMed
  28. 28.↵
    1. Vente MA,
    2. Nijsen JF,
    3. de Wit TC,
    4. et al
    . Clinical effects of transcatheter hepatic arterial embolization with holmium-166 poly(l-lactic acid) microspheres in healthy pigs. Eur J Nucl Med Mol Imaging. 2008;35:1259–1271.
    OpenUrlCrossRefPubMed
  29. 29.↵
    1. Prince JF,
    2. van Rooij R,
    3. Bol GH,
    4. de Jong HW,
    5. van den Bosch MA,
    6. Lam MG
    . Safety of a scout dose preceding hepatic radioembolization with 166Ho microspheres. J Nucl Med. 2015;56:817–823.
    OpenUrlAbstract/FREE Full Text
  30. 30.↵
    1. Kim JK,
    2. Han KH,
    3. Lee JT,
    4. et al
    . Long-term clinical outcome of phase IIb clinical trial of percutaneous injection with holmium-166/chitosan complex (Milican) for the treatment of small hepatocellular carcinoma. Clin Cancer Res. 2006;12:543–548.
    OpenUrlAbstract/FREE Full Text
  31. 31.↵
    1. Dadachova E,
    2. Mirzadeh S,
    3. Lambrecht RM,
    4. Hetherington EL,
    5. Knapp FF
    . Separation of carrier-free holmium-166 from neutron-irradiated dysprosium targets. Anal Chem. 1994;66:4272–4277.
    OpenUrl
  32. 32.↵
    1. Li WP,
    2. Smith CJ,
    3. Cutler CS,
    4. Hoffman TJ,
    5. Ketring AR,
    6. Jurisson SS
    . Aminocarboxylate complexes and octreotide complexes with no carrier added 177Lu, 166Ho and 149Pm. Nucl Med Biol. 2003;30:241–251.
    OpenUrlPubMed
  33. 33.↵
    1. Ueno NT,
    2. de Souza JA,
    3. Booser D,
    4. et al
    . Pilot study of targeted skeletal radiation therapy for bone-only metastatic breast cancer. Clin Breast Cancer. 2009;9:173–177.
    OpenUrlCrossRefPubMed
  34. 34.↵
    1. Rajendran JG,
    2. Eary JF,
    3. Bensinger W,
    4. Durack LD,
    5. Vernon C,
    6. Fritzberg A
    . High-dose 166Ho-DOTMP in myeloablative treatment of multiple myeloma: pharmacokinetics, biodistribution, and absorbed dose estimation. J Nucl Med. 2002;43:1383–1390.
    OpenUrlAbstract/FREE Full Text
  35. 35.↵
    1. Lehenberger S,
    2. Barkhausen C,
    3. Cohrs S,
    4. et al
    . The low-energy beta− and electron emitter 161Tb as an alternative to 177Lu for targeted radionuclide therapy. Nucl Med Biol. 2011;38:917–924.
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. Champion C,
    2. Quinto MA,
    3. Morgat C,
    4. Zanotti-Fregonara P,
    5. Hindie E
    . Comparison between three promising β-emitting radionuclides, 67Cu, 47Sc and 161Tb, with emphasis on doses delivered to minimal residual disease. Theranostics. 2016;6:1611–1618.
    OpenUrl
  37. 37.↵
    1. Müller C,
    2. Zhernosekov K,
    3. Köster U,
    4. et al
    . A unique matched quadruplet of terbium radioisotopes for PET and SPECT and for α- and β−-radionuclide therapy: an in vivo proof-of-concept study with a new receptor-targeted folate derivative. J Nucl Med. 2012;53:1951–1959.
    OpenUrlAbstract/FREE Full Text
  38. 38.↵
    1. Müller C,
    2. Reber J,
    3. Haller S,
    4. et al
    . Direct in vitro and in vivo comparison of 161Tb and 177Lu using a tumour-targeting folate conjugate. Eur J Nucl Med Mol Imaging. 2014;41:476–485.
    OpenUrlCrossRefPubMed
  39. 39.
    1. Grünberg J,
    2. Lindenblatt D,
    3. Dorrer H,
    4. et al
    . Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model. Eur J Nucl Med Mol Imaging. 2014;41:1907–1915.
    OpenUrlCrossRefPubMed
  40. 40.↵
    1. Haller S,
    2. Pellegrini G,
    3. Vermeulen C,
    4. et al
    . Contribution of Auger/conversion electrons to renal side effects after radionuclide therapy: preclinical comparison of 161Tb-folate and 177Lu-folate. EJNMMI Res. 2016;6:13.
    OpenUrl
  41. 41.↵
    1. Allen BJ,
    2. Blagojevic N
    . Alpha- and beta-emitting radiolanthanides in targeted cancer therapy: the potential role of terbium-149. Nucl Med Commun. 1996;17:40–47.
    OpenUrlPubMed
  42. 42.↵
    1. Beyer GJ,
    2. Comor JJ,
    3. Dakovic M,
    4. et al
    . Production routes of the alpha emitting 149Tb for medical application. Radiochim Acta. 2002;90:247–252.
    OpenUrlCrossRef
  43. 43.↵
    1. Beyer GJ,
    2. Miederer M,
    3. Vranjes-Durić S,
    4. et al
    . Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab. Eur J Nucl Med Mol Imaging. 2004;31:547–554.
    OpenUrlCrossRefPubMed
  44. 44.↵
    1. Müller C,
    2. Reber J,
    3. Haller S,
    4. et al
    . Folate receptor targeted alpha-therapy using terbium-149. Pharmaceuticals (Basel). 2014;7:353–365.
    OpenUrl
  45. 45.↵
    1. Müller C,
    2. Vermeulen C,
    3. Köster U,
    4. et al
    . Alpha-PET with terbium-149: evidence and perspectives for radiotheragnostics [letter]. EJNMMI Radiopharm Chem. 2016;1:5.
    OpenUrl
  46. 46.↵
    1. Máthé D,
    2. Szigeti K,
    3. Hegedus N,
    4. et al
    . Production and in vivo imaging of 203Pb as a surrogate isotope for in vivo 212Pb internal absorbed dose studies. Appl Radiat Isot. 2016;114:1–6.
    OpenUrl
  47. 47.↵
    1. Atcher RW,
    2. Friedman AM,
    3. Hines JJ
    . An improved generator for the production of 212Pb and 212Bi from 224Ra. Int J Rad Appl Instrum A. 1988;39:283–286.
    OpenUrlCrossRefPubMed
  48. 48.↵
    1. Yong K,
    2. Brechbiel M
    . Application of 212Pb for targeted α-particle therapy (TAT): pre-clinical and mechanistic understanding through to clinical translation. AIMS Med Sci. 2015;2:228–245.
    OpenUrl
  49. 49.↵
    1. Meredith RF,
    2. Torgue J,
    3. Azure MT,
    4. et al
    . Pharmacokinetics and imaging of 212Pb-TCMC-trastuzumab after intraperitoneal administration in ovarian cancer patients. Cancer Biother Radiopharm. 2014;29:12–17.
    OpenUrlCrossRefPubMed
  50. 50.↵
    1. Meredith R,
    2. Torgue J,
    3. Shen S,
    4. et al
    . Dose escalation and dosimetry of first-in-human α radioimmunotherapy with 212Pb-TCMC-trastuzumab. J Nucl Med. 2014;55:1636–1642.
    OpenUrlAbstract/FREE Full Text
  51. 51.↵
    1. Elgqvist J,
    2. Frost S,
    3. Pouget J-P,
    4. Albertsson P
    . The potential and hurdles of targeted alpha therapy: clinical trials and beyond. Front Oncol. 2014;3:324.
    OpenUrlPubMed
  52. 52.↵
    1. Morgenstern A,
    2. Bruchertseifer F,
    3. Apostolidis C
    . Targeted alpha therapy with 213Bi. Curr Radiopharm. 2011;4:295–305.
    OpenUrlCrossRefPubMed
  53. 53.↵
    1. Apostolidis C,
    2. Molinet R,
    3. McGinley J,
    4. Abbas K,
    5. Mollenbeck J,
    6. Morgenstern A
    . Cyclotron production of Ac-225 for targeted alpha therapy. Appl Radiat Isot. 2005;62:383–387.
    OpenUrlPubMed
  54. 54.↵
    1. Boll RA,
    2. Malkemus D,
    3. Mirzadeh S
    . Production of actinium-225 for alpha particle mediated radioimmunotherapy. Appl Radiat Isot. 2005;62:667–679.
    OpenUrlPubMed
  55. 55.↵
    1. Weidner JW,
    2. Mashnik SG,
    3. John KD,
    4. et al
    . 225Ac and 223Ra production via 800 MeV proton irradiation of natural thorium targets. Appl Radiat Isot. 2012;70:2590–2595.
    OpenUrlCrossRefPubMed
  56. 56.↵
    1. Zhuikov BL,
    2. Kalmykov SN,
    3. Ermolaev SV,
    4. et al
    . Production of 225Ac and 223Ra by irradiation of Th with accelerated protons. Radiochemistry. 2011;53:73–80.
    OpenUrl
  57. 57.↵
    1. Koch L,
    2. Apostolidis C,
    3. Janssens W,
    4. Molinet R,
    5. Van Geel J
    . Production of Ac-225 and application of the Bi-213 daughter in cancer therapy. Czechoslovak J Phys. 1999;49(suppl 1):817–822.
    OpenUrl
  58. 58.↵
    1. Melville G,
    2. Allen BJ
    . Cyclotron and linac production of Ac-225. Appl Radiat Isot. 2009;67:549–555.
    OpenUrlPubMed
  59. 59.↵
    1. de Kruijff RM,
    2. Wolterbeek HT,
    3. Denkova AG
    . A critical review of alpha radionuclide therapy: how to deal with recoiling daughters? Pharmaceuticals (Basel). 2015;8:321–336.
    OpenUrl
  60. 60.
    1. Miederer M,
    2. McDevitt MR,
    3. Sgouros G,
    4. Kramer K,
    5. Cheung NK,
    6. Scheinberg DA
    . Pharmacokinetics, dosimetry, and toxicity of the targetable atomic generator, 225Ac-HuM195, in nonhuman primates. J Nucl Med. 2004;45:129–137.
    OpenUrlAbstract/FREE Full Text
  61. 61.↵
    1. Aghevlian S,
    2. Boyle AJ,
    3. Reilly RM
    . Radioimmunotherapy of cancer with high linear energy transfer (LET) radiation delivered by radionuclides emitting α-particles or Auger electrons. Adv Drug Deliv Rev. 2017;109:102–118.
    OpenUrl
  62. 62.↵
    1. Wadas TJ,
    2. Pandya DN,
    3. Solingapuram Sai KK,
    4. Mintz A
    . Molecular targeted alpha-particle therapy for oncologic applications. AJR. 2014;203:253–260.
    OpenUrl
  63. 63.↵
    1. McDevitt MR,
    2. Ma D,
    3. Lai LT,
    4. et al
    . Tumor therapy with targeted atomic nanogenerators. Science. 2001;294:1537–1540.
    OpenUrlAbstract/FREE Full Text
  64. 64.↵
    1. Miederer M,
    2. Henriksen G,
    3. Alke A,
    4. et al
    . Preclinical evaluation of the alpha-particle generator nuclide 225Ac for somatostatin receptor radiotherapy of neuroendocrine tumors. Clin Cancer Res. 2008;14:3555–3561.
    OpenUrlAbstract/FREE Full Text
  65. 65.↵
    1. Borchardt PE,
    2. Yuan RR,
    3. Miederer M,
    4. McDevitt MR,
    5. Scheinberg DA
    . Targeted actinium-225 in vivo generators for therapy of ovarian cancer. Cancer Res. 2003;63:5084–5090.
    OpenUrlAbstract/FREE Full Text
  66. 66.↵
    1. Jurcic JG,
    2. Rosenblat TL,
    3. McDevitt MR,
    4. et al
    . Phase I trial of the targeted alpha-particle nano-generator actinium-225 (225Ac-lintuzumab) (anti-CD33; HuM195) in acute myeloid leukemia (AML) [abstract]. J Clin Oncol. 2011;29(suppl):6516.
    OpenUrl
  67. 67.↵
    1. Franz B,
    2. Rosenblat TL,
    3. McDevitt MR,
    4. et al
    . Phase I trial of the targeted alpha-particle nano-generator actinium-225 (Ac-225)-lintuzumab (anti-CD33; HuM195) in acute myeloid leukemia (AML). Blood. 2011;118:348–357.
    OpenUrlAbstract/FREE Full Text
  68. 68.↵
    1. Kratochwil C,
    2. Bruchertseifer F,
    3. Giesel FL,
    4. et al
    . 225Ac-PSMA-617 for PSMA-targeted alpha-radiation therapy of metastatic castration-resistant prostate cancer. J Nucl Med. 2016;57:1941–1944.
    OpenUrlAbstract/FREE Full Text
  69. 69.↵
    1. Kratochwil C,
    2. Bruchertseifer F,
    3. Giesel F,
    4. Apostolidis C,
    5. Haberkorn U,
    6. Morgenstern A
    . Dose escalation experience with 225Ac-PSMA-617 in PSMA targeting alpha-radiation therapy of patients with mCRPC. Eur J Nucl Med Mol Imaging. 2016;43(suppl 1):S51.
    OpenUrl
  70. 70.↵
    1. Kratochwil C,
    2. Bruchertseifer F,
    3. Giesel F,
    4. Apostolidis C,
    5. Haberkorn U,
    6. Morgenstern A
    . 225Ac-PSMA-617 for PSMA targeting alpha-radiation therapy of 28 patients with mCRPC. Eur J Nucl Med Mol Imaging. 2016;43(suppl 1):S137.
    OpenUrl
  71. 71.↵
    1. Cordier D,
    2. Forrer F,
    3. Bruchertseifer F,
    4. et al
    . Targeted alpha-radionuclide therapy of functionally critically located gliomas with 213Bi-DOTA-[Thi8,Met(O2)11]-substance P: a pilot trial. Eur J Nucl Med Mol Imaging. 2010;37:1335–1344.
    OpenUrlCrossRefPubMed
  72. 72.↵
    1. Kratochwil C,
    2. Giesel FL,
    3. Bruchertseifer F,
    4. et al
    . 213Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience. Eur J Nucl Med Mol Imaging. 2014;41:2106–2119.
    OpenUrlCrossRefPubMed
  73. 73.↵
    1. Rosenblat TL,
    2. McDevitt MR,
    3. Mulford DA,
    4. et al
    . Sequential cytarabine and alpha-particle immunotherapy with bismuth-213-lintuzumab (HuM195) for acute myeloid leukemia. Clin Cancer Res. 2010;16:5303–5311.
    OpenUrlAbstract/FREE Full Text
  74. 74.
    1. Pillai MR,
    2. Chakraborty S,
    3. Das T,
    4. Venkatesh M,
    5. Ramamoorthy N
    . Production logistics of 177Lu for radionuclide therapy. Appl Radiat Isot. 2003;59:109–118.
    OpenUrlCrossRefPubMed
  75. 75.
    1. Lebedev NA,
    2. Novgorodov AF,
    3. Misiak R,
    4. Brockmann J,
    5. Rösch F
    . Radiochemical separation of no-carrier-added 177Lu as produced via the 176Yb(n,γ)177Yb→177Lu process. Appl Radiat Isot. 2000;53:421–425.
    OpenUrlPubMed
  76. 76.
    1. Yagi M,
    2. Kondo K
    . Preparation of carrier-free 67Cu by the 68Zn(γ,p) reaction. Int J Appl Radiat Isot. 1978;29:757–759.
    OpenUrl
  77. 77.
    1. Mirzadeh S,
    2. Mausner LF,
    3. Srivastava SC
    . Production of no-carrier added 67Cu. Int J Rad Appl Instrum A. 1986;37:29–36.
    OpenUrlPubMed
  78. 78.
    1. Kozempel J,
    2. Abbas K,
    3. Simonelli F,
    4. Bulgheroni A,
    5. Holzwarth U,
    6. Gibson N
    . Preparation of 67Cu via deuteron irradiation of 70Zn. Radiochim Acta. 2012;100:419–423.
    OpenUrl
  • Received for publication February 7, 2017.
  • Accepted for publication March 13, 2017.
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Journal of Nuclear Medicine: 58 (Supplement 2)
Journal of Nuclear Medicine
Vol. 58, Issue Supplement 2
September 1, 2017
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Therapeutic Radiometals Beyond 177Lu and 90Y: Production and Application of Promising α-Particle, β−-Particle, and Auger Electron Emitters
Cristina Müller, Nicholas P. van der Meulen, Martina Benešová, Roger Schibli
Journal of Nuclear Medicine Sep 2017, 58 (Supplement 2) 91S-96S; DOI: 10.2967/jnumed.116.186825

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Therapeutic Radiometals Beyond 177Lu and 90Y: Production and Application of Promising α-Particle, β−-Particle, and Auger Electron Emitters
Cristina Müller, Nicholas P. van der Meulen, Martina Benešová, Roger Schibli
Journal of Nuclear Medicine Sep 2017, 58 (Supplement 2) 91S-96S; DOI: 10.2967/jnumed.116.186825
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  • Article
    • Abstract
    • COPPER-67
    • SCANDIUM-47
    • HOLMIUM-166
    • TERBIUM-161
    • TERBIUM-149
    • LEAD-212 (AND BISMUTH 212)
    • ACTINIUM-225
    • BISMUTH-213
    • CONCLUSION
    • DISCLOSURE
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Keywords

  • radiometals
  • α-particles
  • β−-particles
  • Auger electrons
  • radionuclide therapy
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