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.