Bulk production and evaluation of high specific activity 186gRe for cancer therapy using enriched 186WO3 targets in a proton beam

Mastren, Tara; Radchenko, Valery; Bach, H.; Balkin, Ethan R.; Birnbaum, Eva R.; Brugh, Mark; Engle, Jonathan W.; Gott, Matthew; Guthrie, John; Hennkens, Heather M.; John, Kevin D.; Ketring, Alan R.; Kuchuk, Marina; Maassen, Joel R.; Naranjo, C.M.; Nortier, F.M.; Phelps, Tim; Jurisson, Silvia S.; Wilbur, D. Scott; Fassbender, Michael E.

doi:10.1016/j.nucmedbio.2017.02.006

Cited by 20 publications

(10 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rhenium beta-emitting isotopes, 186 Re ( t 1/2 = 89.2 h, β – 1.075 ΜeV) and 188 Re ( t 1/2 = 17.0 h, β – 2.11 ΜeV), are applied in oncology, typically for bone pain palliation radiotherapy in cancer patients with skeletal metastases, , and are considered the therapeutic counterparts of 99m Tc due to their similar physical and chemical properties. Low specific activity 186 Re can be produced in a nuclear reactor via the 185 Re(n,γ) 186 Re neutron capture reaction, while production of high specific activity 186 Re via the 186 W(p,n) 186 Re high current proton beam reaction is also feasible . Generator-produced 188 Re is currently available through a 188 W/ 188 Re generator, similar to the 99 Mo/ 99m Tc generator, with a long shelf-life of more than six months ( t 1/2 = 69.4 days for 188 W) …”

Section: Introductionmentioning

confidence: 99%

“…Low specific activity 186 Re can be produced in a nuclear reactor via the 185 Re(n,γ) 186 Re neutron capture reaction, while production of high specific activity 186 Re via the 186 W(p,n) 186 Re high current proton beam reaction is also feasible. 4 Generator-produced 188 Re is currently available through a 188 W/ 188 Re generator, similar to the 99 Mo/ 99m Tc generator, with a long shelf-life of more than six months (t 1/2 = 69.4 days for 188 W). 5 Technetium and rhenium both possess rich redox chemistry, and organometallic complexes of the general formula fac-[M I (CO) 3 (k 3 -L)] [M = 99m Tc, 186 Re, 188 Re] have received attention for more than two decades; these complexes exhibit excellent in vivo stability and good pharmacokinetics with fast blood and tissue clearance.…”

Section: ■ Introductionmentioning

confidence: 99%

See 1 more Smart Citation

NOTA and NODAGA [^99mTc]Tc- and [¹⁸⁶Re]Re-Tricarbonyl Complexes: Radiochemistry and First Example of a [^99mTc]Tc-NODAGA Somatostatin Receptor-Targeting Bioconjugate

et al. 2018

Self Cite

View full text Add to dashboard Cite

With the long-term goal of developing theranostic agents for applications in nuclear medicine, in this work we evaluated the well-known NOTA and NODAGA chelators as bifunctional chelators (BFCs) for the [99mTc/186Re]Tc/Re-tricarbonyl core. In particular, we report model complexes of the general formula fac-[M(L)(CO)3]+ (M = Re, 99mTc, 186Re) where L denotes NOTA-Pyr (1) or NODAGA-Pyr (2), which are derived from conjugation of NOTA/NODAGA with pyrrolidine (Pyr). Further, as proof-of-principle, we synthesized the peptide bioconjugate NODAGA-sst2-ANT (3) and explored its complexation with the fac-[Re(CO)3]+ and fac-[99mTc][Tc(CO)3]+ cores; sst2-ANT denotes the somatostatin receptor (SSTR) antagonist 4-NO2-Phe-c(DCys-Tyr-DTrp-Lys-Thr-Cys)-DTyr-NH2. Rhenium complexes Re-1 through Re-3 were synthesized and characterized spectroscopically, and receptor binding affinity was demonstrated for Re-3 in SSTR-expressing cells (AR42J, IC50 = 91 nM). Radiolabeled complexes [99mTc]Tc/[186Re]Re-1/2 and [99mTc]Tc-3 were prepared in high radiochemical yield (>90%, determined by radio-HPLC) by reacting [99mTc]/[186Re][Tc/Re(OH2)3(CO)3]+ with 1–3 and correlated well with the respective Re-1 through Re-3 standards in comparative HPLC studies. All radiotracers remained intact through 24 h (99mTc-labeled complexes) or 48 h (186Re-labeled complexes) against 1 mM l-histidine and 1 mM l-cysteine (pH 7.4, 37 °C). Similarly, rat serum stability studies displayed no decomposition and low nonspecific binding of 9–24% through 4 h. Biodistribution of [99mTc]Tc-3 in healthy CF-1 mice demonstrated a favorable pharmacokinetic profile. Rapid clearance was observed within 1 h post-injection, predominantly via the renal system (82% of the injected dose was excreted in urine by 1 h), with low kidney retention (% ID/g: 11 at 1 h, 5 at 4 h, and 1 at 24 h) and low nonspecific uptake in other organs/tissues. Our findings establish NOTA and NODAGA as outstanding BFCs for the fac-[M(CO)3]+ core in the design and development of organometallic radiopharmaceuticals. Future in vivo studies of [99mTc]Tc- and [186Re]Re-tricarbonyl complexes of NODAGA/NOTA-biomolecule conjugates will further probe the potential of these chelates for nuclear medicine applications in diagnostic imaging and targeted radiotherapy, respectively.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

NOTA and NODAGA [^99mTc]Tc- and [¹⁸⁶Re]Re-Tricarbonyl Complexes: Radiochemistry and First Example of a [^99mTc]Tc-NODAGA Somatostatin Receptor-Targeting Bioconjugate

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…This study demonstrates the difficulty of finding available chelating agents for Rhenium which would be compatible with the humanized or human antibodies. As multiple radioactive isotopes of rhenium (186, 188, and 189) 23 are becoming available for use in RIT of cancerfurther research on developing efficient BCAs for Rhenium is warranted.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of N-Succinimidyl S-Acetylthioacetate Ligand for Radiolabeling of Humanized Antibodies with¹⁸⁸Rhenium

Kjh

Jiao

et al. 2018

Cancer Biotherapy and Radiopharmaceuticals

View full text Add to dashboard Cite

Radioimmunotherapy offers an effective way to direct ionizing radiation to cancer cells through attachment of radionuclides to antibodies while limiting negative effects of off-target irradiation. This, however, requires effective facile methods for attachment of therapeutic radionuclides onto antibodies. Herein, the authors report their efforts in evaluating N-succinimidyl S-acetylthioacetate (SATA), a commercially available reagent, for use as a bifunctional chelating agent (BCA) to attach Rhenium (Re) onto h8C3, a humanized IgG antibody that can effectively target extracellular melanin present in malignant melanoma. Micro single photon emission computer tomography/computer tomography was used to determine an effective timeline for antibody uptake in B16-F10 tumor bearing C57BL6 mice guiding the selection of Re with its 16.9 h physical half-life. Radio instant thin layer chromatography coupled with radio high-performance liquid chromatography was used to assess radioisotope incorporation, as well as stability during the labeling process for SATA conjugated h8C3. It was determined that despite the relatively mild conditions used, incorporation of the SATA conjugate resulted in antibody instability during labeling requiring a different BCA to facilitate rhenium incorporation onto the antibodies.

show abstract

“…A real theranostic application of this radionuclide, however, cannot be achieved because of lack of availability of a positron‐emitting isotope of Re. Nevertheless, there is optimism that the therapeutic uptake of this radionuclide could be quantified through SPECT imaging …”

Section: Novel Radionuclides For Internal Radiotherapymentioning

confidence: 99%

“…Nevertheless, there is optimism that the therapeutic uptake of this radionuclide could be quantified through SPECT imaging. 118 The production of 186 Re in no-carrier-added form has hitherto been investigated using 2 methods, namely, 186 W(p,n) 186 Re and 186 W(d,2n) 186 Re. Most of the studies deal with nuclear reaction cross section measurements.…”

Section: Re (T ½ = 378 D)mentioning

confidence: 99%

Development of novel radionuclides for medical applications

Qaim

Spahn

2017

Labelled Comp Radiopharmac

View full text Add to dashboard Cite

Medical radionuclide production technology is well established. There is, however, a constant need for further development of radionuclides. The present efforts are mainly devoted to nonstandard positron emitters (eg, Cu, Y, I, and Se) and novel therapeutic radionuclides emitting low-range β particles (eg, Cu and Re), conversion or Auger electrons (eg, Sn and Br), and α particles (eg, Ac). A brief account of various aspects of development work (ie, nuclear data, targetry, chemical processing, and quality control) is given. For each radionuclide under consideration, the status of technology for clinical scale production is discussed. The increasing need of intermediate-energy multiple-particle accelerating cyclotrons is pointed out.

show abstract

Bulk production and evaluation of high specific activity 186gRe for cancer therapy using enriched 186WO3 targets in a proton beam

Abstract: We report a preliminary study of the large-scale production and novel anion exchange based chemical recovery of high specific activity Re from enrichedWO targets in a high-intensity proton beam with exceptional chemical recovery and radiochemical purity.

Cited by 20 publications

References 32 publications

NOTA and NODAGA [^99mTc]Tc- and [¹⁸⁶Re]Re-Tricarbonyl Complexes: Radiochemistry and First Example of a [^99mTc]Tc-NODAGA Somatostatin Receptor-Targeting Bioconjugate

NOTA and NODAGA [^99mTc]Tc- and [¹⁸⁶Re]Re-Tricarbonyl Complexes: Radiochemistry and First Example of a [^99mTc]Tc-NODAGA Somatostatin Receptor-Targeting Bioconjugate

Evaluation of N-Succinimidyl S-Acetylthioacetate Ligand for Radiolabeling of Humanized Antibodies with¹⁸⁸Rhenium

Development of novel radionuclides for medical applications

Contact Info

Product

Resources

About

Bulk production and evaluation of high specific activity 186gRe for cancer therapy using enriched 186WO3 targets in a proton beam

Abstract: We report a preliminary study of the large-scale production and novel anion exchange based chemical recovery of high specific activity Re from enrichedWO targets in a high-intensity proton beam with exceptional chemical recovery and radiochemical purity.

Cited by 20 publications

References 32 publications

NOTA and NODAGA [99mTc]Tc- and [186Re]Re-Tricarbonyl Complexes: Radiochemistry and First Example of a [99mTc]Tc-NODAGA Somatostatin Receptor-Targeting Bioconjugate

NOTA and NODAGA [99mTc]Tc- and [186Re]Re-Tricarbonyl Complexes: Radiochemistry and First Example of a [99mTc]Tc-NODAGA Somatostatin Receptor-Targeting Bioconjugate

Evaluation of N-Succinimidyl S-Acetylthioacetate Ligand for Radiolabeling of Humanized Antibodies with188Rhenium

Development of novel radionuclides for medical applications

Contact Info

Product

Resources

About

NOTA and NODAGA [^99mTc]Tc- and [¹⁸⁶Re]Re-Tricarbonyl Complexes: Radiochemistry and First Example of a [^99mTc]Tc-NODAGA Somatostatin Receptor-Targeting Bioconjugate

NOTA and NODAGA [^99mTc]Tc- and [¹⁸⁶Re]Re-Tricarbonyl Complexes: Radiochemistry and First Example of a [^99mTc]Tc-NODAGA Somatostatin Receptor-Targeting Bioconjugate

Evaluation of N-Succinimidyl S-Acetylthioacetate Ligand for Radiolabeling of Humanized Antibodies with¹⁸⁸Rhenium