Radiopharmaceuticals & theranostics

01Overview and value chain

Markers: [EC: Euratom Treaty & API Guidelines | OECD: bio-pharma | Regulator: FDA (US), EMA (EU), NMPA (CN), IAEA]

Radiopharmaceuticals and theranostics pair a tumor-targeting vector — a monoclonal antibody, peptide or small molecule — with a radioactive isotope, using a diagnostic isotope for PET/CT tumor imaging and a therapeutic isotope on the same vector for targeted cell killing. Novartis’s Pluvicto (177Lu-PSMA-617) is the sector’s commercial proof point, and the company is backing it with a planned $23 billion five-year manufacturing investment, including a new 70,000-square-foot Indianapolis facility that is now its largest and most advanced radioligand-therapy production site. Germany’s ITM supplies non-carrier-added Lutetium-177 (n.c.a. 177Lu) under long-running arrangements — including a collaboration with the Institut Laue-Langevin dating to 2009 — and has signed a fresh supply agreement with Radiopharm Theranostics to support its clinical pipeline. On the alpha-emitter side, Bristol Myers Squibb’s RayzeBio unit is developing SSTR2-targeted radiopharmaceutical therapies for gastroenteropancreatic neuroendocrine tumors and has built a dedicated Indianapolis hub for end-to-end manufacturing and on-demand RayzeBio drug-product delivery. In imaging, Curium has launched PYLCLARI (piflufolastat [18F], also marketed as Pylarify in the US) — a PSMA-targeted PET tracer for prostate cancer — commercially in Spain and Germany.

The key directions of radiopharmaceuticals and theranostics are:

1. Beta-emitter targeted therapy (Lutetium-177): using 177Lu, whose beta particles travel roughly 1-2 mm in tissue, to damage cancer-cell DNA while sparing surrounding healthy tissue — the basis of Pluvicto and Lutathera.
2. Targeted alpha therapy (TAT): using alpha emitters such as Actinium-225 or Lead-212, whose high-energy, ultra-short-range (under 100 micrometers) particles cause irreparable double-strand DNA breaks even from a single hit, overcoming radioresistance.
3. Precision vector targeting: using highly specific delivery vectors — chiefly PSMA on prostate-cancer cells and somatostatin receptors (SSTR) on neuroendocrine tumors — chelated via DOTA or Macropa.
4. PET/CT diagnostic pairing: using a short-lived diagnostic isotope on the same vector to image the tumor before or alongside therapy, the “theranostic” logic of seeing what you treat.

Sectoral value chain

[Isotope Production (Reactor)] ──> [Chelator & Vector Synthesis] ──> [Hot-Cell Radiolabeling]
                │                                     │                                  │
       (Lu-177/Ac-225, targets)              (DOTA/PSMA, peptides)                (Radiochemical purity)
                                                                                           │
[Clinical Administration (GMP)] <─── [Downstream Purification & Dosing] <─────────────────┘

Value chain levels

Cross-cutting technologies of the sector:

• Macrocyclic chelation (coordination chemistry): organic macrocycle “cages” (DOTA, Macropa, crown ethers) that tightly bind trivalent radiometal ions (177Lu3+, 225Ac3+) through nitrogen and oxygen coordination bonds, preventing dissociation of free toxic isotope in the patient’s blood.
• No-carrier-added Lutetium-177 (n.c.a. 177Lu) production: irradiating a highly enriched Ytterbium-176 target with thermal neutrons in a reactor, then chemically separating the resulting Lu-177 from Yb to achieve the highest specific activity with no long-lived 177mLu contamination.
• Automated hot-cell radiosynthesis modules: sealed, negative-pressure lead enclosures with automated cartridge-based radiosynthesis systems, letting all mixing, heating, column purification and sterile filtration run remotely without manual radiation contact.

02US

The US is the world’s largest theranostics market and is actively working to resolve a therapeutic-isotope supply bottleneck.

Pluvicto commercial scale-up, alpha-emitter M&A, Actinium-225 supply expansion

• Novartis: backs Pluvicto’s commercial success with a planned $23 billion five-year manufacturing investment, including a new 70,000-square-foot Indianapolis facility that is now its largest and most advanced radioligand-therapy production site.
• RayzeBio (Bristol Myers Squibb): develops SSTR2-targeted radiopharmaceutical therapies for gastroenteropancreatic neuroendocrine tumors and operates a dedicated Indianapolis hub for end-to-end manufacturing and on-demand delivery of its clinical-stage RPT candidates.
• Actinium-225 supply: the US Department of Energy and private companies are investing in Radium-226 accelerator-irradiation routes and legacy Thorium-229 reprocessing to scale global Actinium-225 production for targeted alpha therapy.
• Perspective Therapeutics: develops Lead-212-based peptide radiopharmaceuticals for melanoma and neuroendocrine cancers, a leading US player in the alpha-emitter space.

03CN

China treats radiopharmaceutical self-sufficiency as a strategic health priority, building domestic reactor and cyclotron capacity while its pharmaceutical majors expand into nuclear oncology.

isotope self-sufficiency programs, domestic theranostic manufacturing, SIRT clinical expansion

• Grand Pharmaceutical: markets SIR-Spheres Yttrium-90 microspheres (Yigantai) for selective internal radiation therapy of liver cancer, and its US DOORwaY90 clinical trial met its primary endpoint for unresectable hepatocellular carcinoma; the company is building China’s largest radiopharmaceutical production base in Wuhan.
• Isotope independence programs: China’s national medical-isotope development program is building dedicated research reactors and cyclotrons aimed at ending reliance on imported Lutetium-177 and Iodine-131.
• Domestic isotope purification research: Chinese researchers have developed an automated system for simultaneous separation and purification of the medical isotopes Actinium-225 and Radium-223, supporting future alpha-emitter production capacity.

04EU

The EU, and Germany in particular, is the historical birthplace of theranostics, combining the world’s leading academic school with the dominant global isotope supplier.

PSMA discovery science, Lutetium-177 supply monopoly, PET tracer commercialization

• DKFZ Heidelberg: the German Cancer Research Center is where PSMA-617 — the ligand underlying Pluvicto — was discovered, and continues total-synthesis research refining the chemistry behind PSMA-targeted radiotheranostics.
• ITM (Isotopen Technologien München): the world’s leading supplier of non-carrier-added Lutetium-177, with a Lu-177 manufacturing collaboration with the Institut Laue-Langevin dating to 2009 and a fresh 2026 supply agreement with Radiopharm Theranostics.
• Curium: has launched PYLCLARI, a PSMA-targeted 18F PET tracer for prostate cancer, commercially in Spain and Germany, extending its diagnostic-isotope logistics network across Europe.

05Leading companies and research institutes

06Tech stack and innovations

Modern radiopharmaceutical production rests on the following technology stack:

1. Precision bifunctional chelator synthesis (DOTA, Macropa):
   • Bifunctional chelators have a dual structure: a macrocycle that tightly holds the metal ion, and a reactive group (e.g., an NHS ester) that covalently attaches to the peptide vector’s amino group; isomeric purity is critical, since even small changes in macrocycle geometry weaken isotope binding and cause bone-tissue leakage (toxicity).
2. Radiosynthesis in shielded hot cells:
   • Chambers built from 50-100mm lead with leaded-glass windows maintain negative pressure and Class A laminar airflow; the isotope-coordination reaction (e.g., 177Lu with PSMA-617) runs in a single-use automated cartridge module heated to roughly 95°C for 15-30 minutes.
3. Radio-HPLC radiochemical purity control:
   • HPLC coupled in series to a UV detector and a scintillation radio-detector separates the labeled product, free unlabeled peptide, and free unbound isotope within about 5 minutes, confirming radiochemical purity of at least 95% before release.

07Value chains and production pipelines

Industrial pipeline of just-in-time GMP production and delivery of a theranostic radiopharmaceutical

┌───────────────────────────┐      ┌───────────────────────────┐
│ 1. n.c.a. Lu-177 chloride │ ───> │ 2. Automated hot-cell     │
│    delivery to GMP lab     │      │    radiosynthesis           │
└───────────────────────────┘      └───────────────────────────┘
                                                 │
                                                 ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 4. Sterile filtration &   │ <─── │ 3. Radio-HPLC purity      │
│    aseptic fill            │      │    control                  │
└───────────────────────────┘      └───────────────────────────┘
              │
              ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 5. Lead-container packing │ ───> │ 6. Air freight & clinical │
│    & release                │      │    administration          │
└───────────────────────────┘      └───────────────────────────┘

Stage 1: Receiving radioactive raw material at the GMP lab

A lead transport container arrives from a specialized reactor (e.g., ITM in Germany) carrying a vial of ultra-pure, no-carrier-added Lutetium-177 chloride solution in 0.04M hydrochloric acid; incoming QC measures total radioactivity on an ionization chamber and confirms isotopic purity (no long-lived 177mLu) by gamma spectrometry.

Stage 2: Automated hot-cell radiosynthesis

An operator loads a single-use sterile cartridge into a radiosynthesis module inside a lead hot cell; the module automatically doses roughly 100 micrograms of cold precursor vector (e.g., PSMA-617 peptide) in sodium-acetate buffer (pH 5.0-5.5) with a 7.4 GBq dose of Lu-177 chloride, then heats the mixture to 95°C for 15 minutes as the lutetium ions coordinate inside the peptide’s DOTA macrocycle.

Stage 3: Purification and radiochemical QC

The cooled reaction mixture is pumped through a C18 solid-phase extraction cartridge; free unbound Lu-177 washes to waste while the labeled product elutes in a small volume of sterile ethanol, then is diluted with saline containing sodium ascorbate (a radioprotectant against self-radiolysis); an automated sampler injects a 10-microliter aliquot into a radio-HPLC system to confirm radiochemical purity above 95% and free lutetium below 2%.

Stage 4: Sterile filtration and aseptic dose filling

The purified solution passes through an inline 0.22-micron polyethersulfone sterilizing filter, is dosed into a first-hydrolytic-class glass vial, sealed with a rubber stopper and aluminum crimp cap, bubble-point tested for filter integrity, and sampled for an LAL endotoxin test (below 175 EU/dose).

Stage 5: Packing in a shielded lead container

A robotic manipulator places the sealed vial inside a 30mm-thick lead container that absorbs the Lu-177 beta radiation, reducing the external surface dose rate to a safe level (under 0.5 mSv/hr); the container is placed in a certified transport case, labeled with Category II-Yellow radiation hazard markings, and issued a certificate of analysis with exact activity-calibration time.

Stage 6: Air freight and patient administration

Because Lu-177 has a half-life of just 6.7 days (Ac-225, 9.9 days), the product cannot be warehoused; logistics teams provide express, often air-freighted, just-in-time delivery directly to the oncology clinic’s nuclear-medicine department, where a physician measures residual activity, administers the dose intravenously over 10-20 minutes, and monitors the patient in a shielded room before discharge, with therapy response later confirmed by Gallium-68 PET/CT imaging.