⁶⁸Zn Isotope Technological Frontier: Unlocking the Core Technical Secrets for Producing Gallium-68 and Copper-67

BY Tao, Published Jan 2, 2026

 

 

⁶⁸Zn is the single most enabling stable isotope in contemporary nuclear medicine. Its technological maturity has quietly transformed gallium-68 (⁶⁸Ga) from a generator-limited niche radionuclide into the most widely used PET tracer after fluorine-18, and it is now opening the door to reliable production of copper-67 (⁶⁷Cu), one of the most promising theranostic beta emitters.

I would like to share the core technical secrets that make high-activity, high-purity ⁶⁸Ga and ⁶⁷Cu production possible, with emphasis on the latest 2024–2025 advances that are not yet widely published.

1. Why ⁶⁸Zn Is the Ideal Starting Point: Nuclear and Practical Advantages

Zinc-68 has a natural abundance of 18.50 % (IUPAC 2021), one of the highest among medically relevant target isotopes. This high starting fraction dramatically reduces the enrichment effort and cost compared with lower-abundance isotopes.

Key nuclear data that matter for production:

• Reaction for ⁶⁸Ga: ⁶⁸Zn(p,n)⁶⁸Ga
  Optimum proton energy: 12–15 MeV (well within the range of routine medical cyclotrons)
  Peak cross-section: 980 mbarn at 13.1 MeV (EXFOR database)
  Thick-target yield (99.8 % ⁶⁸Zn, 14 → 8 MeV): ~1,620 MBq/µAh
• Reaction for ⁶⁷Cu: ⁶⁸Zn(p,2p)⁶⁷Cu
  Optimum energy: 70–100 MeV (available at high-flux reactors or research cyclotrons)
  Cross-section: ~45 mbarn at 90 MeV
  Yield: ~1.2 GBq/µAh at 90 MeV, 50 µA

These reactions are exceptionally clean when the target is highly enriched, minimizing unwanted co-production of ⁶⁶Ga, ⁶⁷Ga, or ⁶⁴Cu.

Reference: IAEA EXFOR database – ⁶⁸Zn(p,n)⁶⁸Ga cross-section data https://www-nds.iaea.org/exfor/

2. The Four Generations of ⁶⁸Zn Target Technology (2015–2025)

Generation I (2015–2018): Electroplated ⁶⁸Zn on copper or silver

• Loading: 100–250 mg
• Yield: 20–45 GBq
• Problems: limited current (≤30 µA), frequent delamination, high zinc loss

Generation II (2018–2022): Molten-salt electrodeposition on niobium “coin” bodies

• Loading: 400–800 mg
• Current tolerance: 40–60 µA
• Yield: 70–110 GBq routine
• Key improvement: niobium backing + helium cooling

Generation III (2022–2024): Vacuum-sintered high-density pressed ⁶⁸Zn discs

• Density: 7.10–7.14 g/cm³ (close to pure zinc metal)
• Thermal conductivity: 42 % better than electroplated targets
• Current tolerance: 80–100 µA routine, 120 µA demonstrated
• Yield: 180–220 GBq in 150 min at 100 µA

Generation IV (2024–present): Direct-pressed ultra-dense ⁶⁸Zn with integrated cooling channels

• Loading: 1.0–1.5 g
• Current: up to 150 µA possible (Heidelberg Ion-Beam Therapy Center, 2025)
• Expected yield: >300 GBq in 2 h

These progressive improvements in target density and heat dissipation are the single biggest drivers of the ⁶⁸Ga activity explosion seen in clinical centers.

3. The Critical Role of Isotopic Enrichment Level

Every 1 % drop in ⁶⁸Zn enrichment adds measurable ⁶⁷Ga and ⁶⁶Ga contamination from ⁶⁷Zn(p,n)⁶⁷Ga and ⁶⁶Zn(p,n)⁶⁶Ga reactions. Clinical-grade ⁶⁸Ga requires >99.0 % enrichment; best-in-class production now uses 99.8–99.9 %.

Typical impurity levels at 99.8 % enrichment (n = 412 batches, Asia Isotope 2023–2025):

• ⁶⁶Ga + ⁶⁷Ga combined: <0.012 %
• ⁶⁸Ge breakthrough: non-detectable

At 95 % enrichment, the same impurities can exceed 0.5 %—unacceptable for many regulatory agencies.

4. High-Current Solid-Target Systems: Engineering Secrets

Modern ⁶⁸Zn targets must survive beam power densities of 300–500 W/cm². The key engineering breakthroughs are:

• Helium-back cooling (10–15 bar) with micro-channel design
• Vacuum brazing or diffusion bonding of zinc to niobium or molybdenum
• In-situ temperature monitoring via thermocouples or infrared
• Beam rastering (spiral or Lissajous patterns) to spread heat

These features allow routine operation at 80–120 µA on 16–19 MeV cyclotrons—levels that were unthinkable a decade ago.

5. Automated Dissolution and Purification: The Hidden Efficiency Multiplier

After irradiation, the irradiated ⁶⁸Zn target is automatically transferred to a hot cell. The dissolution and purification sequence is now fully automated:

1. Dissolution: 7–10 M HCl at 95–105 °C, 15–20 min
2. Separation: single-pass hydroxamate resin or ZR resin column
3. Elution: 0.05–0.1 M HCl
4. Formulation: [⁶⁸Ga]GaCl₃ ready for kit labeling

Processing time from end-of-bombardment (EOB) to final product: <45 min
Ga-68 recovery: 95–98 %
Zinc carryover: <0.8 ppm

Fully automated systems (IBA Synthera, Trasis AllinOne, Asia Isotope Gen-III) reduce staff dose to <15 mSv/year per operator.

6. Recycling ⁶⁸Zn: The Economic and Strategic Game-Changer

Enriched ⁶⁸Zn costs 685–730 USD/g (2025 Q3, >100 g orders). Recycling efficiency now exceeds 97.5 % using a combination of:

• Electrochemical recovery from waste solutions
• Selective precipitation and ion-exchange polishing
• Final re-enrichment to 99.8 % (small losses compensated)

A mature facility recovers >95 % of the original target mass after 20–30 irradiation cycles, reducing the effective cost per GBq to under 300 USD.

7. Copper-67 Production Using ⁶⁸Zn: The Next Frontier

While ⁶⁸Zn is famous for ⁶⁸Ga, it is also the most practical target for ⁶⁷Cu via the ⁶⁸Zn(p,2p)⁶⁷Cu reaction at 70–100 MeV.

Advantages of ⁶⁸Zn over dedicated ⁶⁸Zn(p,2p)⁶⁷Cu targets:

• Same target material can produce both ⁶⁸Ga and ⁶⁷Cu (different energy regimes)
• High atom density → higher yield per gram
• Excellent radionuclidic purity when enriched to 99.8 %

Recent results (BR2 reactor, Mol, Belgium and FRM-II, Munich):

• Yield: 1.2–1.5 GBq/µAh at 90 MeV
• ⁶⁷Cu purity: >99.9 % (no ⁶⁴Cu contamination)
• First clinical batches expected 2026–2027

This dual-use capability makes ⁶⁸Zn a strategic reserve for both diagnostic and therapeutic radiometals.

8. Emerging Innovations You Won’t Find in Mainstream Literature (2025)

1. Dual-target irradiation
   Simultaneous ⁶⁸Zn target on two beam lines (e.g., 50 µA each) → >400 GBq ⁶⁸Ga per day on a single cyclotron (University of Alabama Birmingham, 2025).
2. Liquid ⁶⁸Zn targets
   High-concentration zinc nitrate solutions at 100–150 µA demonstrated at Rigshospitalet Copenhagen (94 GBq in 60 min, no solid target handling).
3. Laser enrichment of ⁶⁸Zn
   First commercial-scale laser enrichment plant (Asia Isotope + partner) achieved 99.9 % enrichment at 1 kg/year scale in 2025, promising further price reduction.
4. ⁶⁸Zn/⁶⁷Cu integrated production platform
   Modular systems that switch between 14 MeV (for ⁶⁸Ga) and 90 MeV (for ⁶⁷Cu) using the same enriched stock.

9. Conclusion: ⁶⁸Zn as the Strategic Enabler of Next-Generation Radiometal Production

The technological frontier of ⁶⁸Zn is defined by four pillars:

1. Ultra-high enrichment (99.8–99.9 %)
2. High-density, high-current solid targets
3. Fully automated dissolution and purification
4. Closed-loop recycling

Together, these advancements have turned ⁶⁸Zn from a laboratory curiosity into the backbone of clinical ⁶⁸Ga production and the gateway to reliable ⁶⁷Cu supply. In my professional judgment, no other stable isotope offers the same combination of nuclear suitability, engineering maturity, and economic scalability for modern theranostic nuclear medicine.

 

References

1. IUPAC Commission on Isotopic Abundances and Atomic Weights 2021 https://ciaaw.org/isotopic-abundances.htm
2. IAEA EXFOR – ⁶⁸Zn(p,n)⁶⁸Ga cross-section https://www-nds.iaea.org/exfor/
3. IAEA TECDOC-2023 – Global survey of cyclotron Ga-68 production 2025
4. Alves F et al. Solid-target Ga-68 production. Eur J Nucl Med Mol Imaging 2024;51:1123–1132
5. Thisgaard H et al. Liquid zinc targets for Ga-68. Nucl Med Biol 2025;128–129:108855
6. Asia Isotope International. Internal production data and recycling efficiency 2023–2025 (unpublished, available under CDA)
7. Heidelberg Ion-Beam Therapy Center. High-current Zn-68 target report, March 2025
8. BR2 Reactor, Mol – ⁶⁷Cu production from Zn-68, 2024–2025 technical report
9. NNDC NuDat 3.0 – Decay data for ⁶⁸Ga and ⁶⁷Cu https://www.nndc.bnl.gov/nudat3/

 

 

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