— 01 · At a Glance
The emerging pipeline at our centre.
★ In one paragraph
Upcoming theranostics are radionuclide therapies that have moved past laboratory proof-of-concept into early clinical translation, but are not yet regulator-approved as standard care. Most are alpha-emitting isotopes — the same family as the Ac-225 alpha therapies we already offer in our Alpha PSMA and Alpha PRRT programmes — with different physical and supply-chain properties that may make them better suited to specific clinical scenarios.
This page is for patients and referring physicians who want to understand what's coming and how to access it. Each isotope listed below is currently in clinical or late-preclinical development internationally, with our team actively tracking the literature, attending the relevant scientific meetings, and engaging with the global theranostic community.
We accept compassionate-use enquiries for patients with progressive disease who have exhausted regulator-approved standard options and may benefit from an emerging therapy. Eligibility is reviewed case by case at our multidisciplinary tumour board, taking into account the patient's diagnosis, prior treatment, current imaging, and target expression.
— 02 · Pb-212
Lead-212 — the in vivo alpha generator.
Pb-212 is the most advanced of the upcoming alpha-emitting radionuclides. Its emerging clinical role mirrors Ac-225 — the alpha radiation in our existing Alpha PRRT and Alpha PSMA programmes — with three practical advantages that may make it the more accessible alpha isotope long-term:
- Scalable supply. Pb-212 can be eluted from a Ra-224 (radium-224) generator, similar in concept to a Mo-99/Tc-99m generator. This is potentially much more scalable than Ac-225, which depends on extremely limited global supply from a handful of accelerator facilities.
- Single therapeutic alpha. Pb-212 itself is a beta emitter, but it decays through a brief intermediate (Bi-212) that emits one therapeutic alpha. Unlike Ac-225's four-alpha decay chain, this gives a simpler dosimetry profile — potentially predictable in normal tissues.
- Practical half-life. At 10.6 hours, Pb-212 sits between the very short-lived Bi-213 (~46 min) and the longer-lived Ac-225 (10 days). Long enough for biodistribution and dosimetry. Short enough for cleaner end-of-cycle clearance.
How the in vivo generator works.
The therapy delivers Pb-212 attached to a targeting ligand (PSMA-617 for prostate cancer, DOTAMTATE for neuroendocrine tumours). The targeted molecule binds its receptor on the tumour cell. Pb-212 then decays through Bi-212 to release the therapeutic alpha particle at the location where the molecule is already bound — effectively a pre-loaded alpha grenade that triggers in place.
This is why Pb-212 is described as an "in vivo generator" — the patient is dosed with the long-lived precursor, and the short-lived therapeutic alpha is generated inside the tumour cell rather than having to be infused as such (which would be impossible at 60-minute alpha half-life).
212Pb
IN VIVO ALPHA GENERATOR
[Image: Decay chain diagram — Pb-212 (10.6h beta) → Bi-212 (60min) → alpha emission within tumour cell, showing the in vivo generation concept and how the alpha is released at the bound target site]
Pb-212 variants in clinical translation
Two configurations of Pb-212 are most advanced in clinical development. We track both and have administered each at our centre on compassionate use.
For SSTR-positive NETs
212Pb-DOTAMTATE
The Pb-212 analog of Lu-DOTATATE PRRT, paired with the related DOTAMTATE ligand. Currently in the ACTION-1 phase 1/2 trial (sponsored internationally), which has reported encouraging response signals in patients progressing on Lu-DOTATATE. Received FDA fast-track designation in 2024.
For metastatic prostate cancer
212Pb-PSMA-617
The Pb-212 analog of Lu-PSMA-617, currently in early clinical development internationally. Of particular interest as a potential future alternative to Ac-225 PSMA — with cleaner dosimetry and potentially better global supply chain.
— 03 · Th-227
Targeted thorium-227 conjugates.
Thorium-227 (Th-227) is an alpha emitter that decays to radium-223 (the active component of Xofigo, the FDA-approved bone-targeted alpha for prostate cancer bone metastases). Linked to monoclonal antibody targeting ligands — rather than the small-molecule ligands used for PSMA and DOTATATE — Th-227 enables targeted alpha therapy at slowly internalising receptors that small-molecule alphas don't suit.
- Long half-life — 18.7 days. Suited to slowly internalising antibody targeting, where the receptor turns over over days rather than minutes.
- Decay-chain dose — through radium-223 and onwards, contributing additional alpha emissions to total tumour dose.
- Active development programmes — including phase 1 trials against PSMA, CD22, HER2, mesothelin and other antibody targets internationally.
Th-227 is not yet at the patient-access stage in India. We monitor the programme closely and will offer it when global supply and regulatory pathways open up.
— 04 · Active Surveillance
The broader alpha landscape.
Several other alpha-emitting and high-LET isotopes are on our active surveillance list. None are yet at routine clinical translation, but each has specific scientific rationale and ongoing trial activity.
224Ra (Radium-224)
Surveillance
Bone-seeking alpha emitter with mechanism similar to Ra-223 but different decay chain. Used investigationally in diffuse skeletal metastatic disease and as the parent isotope of Pb-212 generators. Limited direct patient use today; supplies enable Pb-212 access.
213Bi (Bismuth-213)
Surveillance
The original alpha emitter used in the first targeted alpha therapies in the late 1990s and 2000s. Very short half-life (~46 minutes) makes routine clinical use logistically challenging. Now mostly superseded by Ac-225 and Pb-212, but remains in selected research settings including the Heidelberg targeted-alpha-NET programme.
211At (Astatine-211)
Surveillance
Halogen-based alpha emitter that chemically resembles iodine — making it potentially compatible with iodine-targeted molecules including MIBG analogs. Several early-phase trials in glioma and ovarian carcinoma internationally. Astatine production requires accelerator infrastructure currently limited to a handful of facilities worldwide.
— 05 · Access
How to enquire about an emerging therapy.
Patients interested in any of the upcoming theranostics described above should request an online or in-person consultation with Dr. Ishita B. Sen. The 30-minute consultation reviews the diagnosis, prior treatment history, current imaging, and disease pattern.
- If your situation may benefit from an emerging therapy on a compassionate-use basis, your case is brought to our multidisciplinary tumour board for review — involving Dr. Sen, Dr. Dharmender Malik, and the referring medical oncologist where applicable.
- If you do not yet qualify for an emerging option, we recommend the appropriate standard-of-care line — usually Lu-PSMA, PRRT, or another regulator-approved radioligand therapy.
- If you have already received standard radioligand therapy and progressed, we discuss the available alpha options (Ac-225 PSMA, Ac-225 PRRT) alongside compassionate-use Pb-212 if your case fits.
★ Honest framing
Upcoming theranostics are not a faster route to a cure. They are options to consider when standard care has been exhausted or where the patient's specific disease pattern may benefit from a different radiation type. We discuss the evidence base, the trade-offs, and the realistic expectations openly — before any patient commits to therapy.
Where we do not have the technical capability or supply for a specific isotope, we say so directly and where appropriate refer the patient onwards to a centre that does.
— 06 · Why We Track These
Frontier oncology is part of our practice.
Theranostic Physicians is a specialist nuclear oncology practice. Tracking the global emerging radioligand pipeline is part of our standard clinical responsibility — it helps us advise patients accurately about what's available today, what's coming next, and what to realistically expect.
Several of our team members participate in international scientific meetings and collaborative research networks where these emerging therapies are developed — from the European Association of Nuclear Medicine (EANM) annual congress to the Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the International Symposium on Radiopharmaceutical Therapy (ISRT).
This page is not a marketing document. It is an honest catalogue of where the field is going, what we can offer today, and what we expect to offer in the near future. We update it as the global pipeline progresses.
Frequently asked questions.
Pb-212 (lead-212) therapy is an emerging form of targeted alpha radionuclide therapy. Pb-212 is itself a beta emitter, but it decays through a short chain to Bi-212 — which is the actual therapeutic alpha emitter. Because Pb-212 has a relatively practical half-life of 10.6 hours (compared to Bi-212's very short ~60 minutes), it functions as an in vivo alpha generator: bound to the targeting ligand, delivered to the tumour cell, and then decaying locally to release the alpha-emitting daughter.
Currently in clinical translation as 212Pb-DOTAMTATE for neuroendocrine tumours (the ACTION-1 trial) and 212Pb-PSMA-617 for metastatic prostate cancer.
Both Pb-212 and Ac-225 deliver alpha radiation to tumour cells via the same theranostic targeting strategy, but they differ in three ways.
Half-life: Pb-212 is 10.6 hours, Ac-225 is 10 days — Pb-212 is much more time-sensitive in supply chain. Daughter chain: Ac-225 decays through four alpha emissions, multiplying dose per molecule; Pb-212 emits one alpha via Bi-212 with no further alphas. Supply: Pb-212 is theoretically scalable from a Ra-224 generator, potentially making it more accessible than Ac-225 globally. Clinical translation of Pb-212 trails Ac-225 by approximately 5 years but is accelerating.
Targeted alpha therapy (TAT) is a class of radionuclide cancer treatments that pair a tumour-targeting molecule (such as PSMA-617 for prostate cancer or DOTATATE for neuroendocrine tumours) with an alpha-emitting radioisotope (such as Ac-225, Pb-212, Th-227, Bi-213, or At-211).
Alpha particles deliver dense ionising radiation over a very short tissue range — typically 50 to 100 micrometres — producing potent cell killing that overwhelms DNA repair mechanisms. The targeting molecule ensures the alpha emission concentrates at the tumour rather than elsewhere in the body.
Pb-212 therapy is available at our centre on a compassionate-use, case-by-case basis for highly selected patients. It is not yet a routine offering — supply chain and regulatory pathways are still being established globally.
We accept enquiries from patients with documented progressive disease on standard radioligand therapy (Lu-PSMA, Lu-DOTATATE) who may benefit from an alpha alternative. Eligibility is reviewed at multidisciplinary tumour board.
ACTION-1 (sponsored by Perspective Therapeutics, formerly Radiomedix) is a phase 1/2 clinical trial of 212Pb-DOTAMTATE in patients with progressive somatostatin-receptor-positive neuroendocrine tumours, including patients who have progressed on standard Lu-DOTATATE PRRT.
Initial published cohorts have demonstrated feasibility, acceptable safety, and meaningful response signal. ACTION-1 received FDA fast-track designation in 2024 reflecting its emerging therapeutic significance.
Targeted thorium therapy uses thorium-227, an alpha emitter that decays to radium-223 (the active component of Xofigo for bone metastases). Th-227 conjugated to targeting antibodies (such as anti-PSMA, anti-CD22, or anti-HER2) is being developed in several phase 1 trials internationally.
Bayer led much of the early thorium conjugate research. The advantage over Ac-225 is the 18.7 day half-life of Th-227, which simplifies logistics for slowly internalising targets like antibodies.
Patients interested in upcoming theranostics should request a consultation with Dr. Ishita B. Sen. The initial review covers the diagnosis, prior treatment history, current imaging, and disease pattern.
If a patient's situation may benefit from an emerging therapy on a compassionate-use basis, the case is brought to the multidisciplinary tumour board for review. Where the patient does not yet qualify for an emerging option, we recommend the appropriate standard-of-care line — usually Lu-PSMA, PRRT, or another regulator-approved radioligand therapy.
Theranostic Physicians is a specialist nuclear oncology practice. Tracking the global emerging radioligand pipeline is part of our standard clinical responsibility — it helps us advise patients accurately about what's available, what's coming, and what to expect from current therapies versus future options.
Several team members participate in international scientific meetings and collaborative research networks where these emerging therapies are developed.
IS
[Image: Dr. Sen portrait]
Written & Medically Reviewed By
Dr. Ishita B. Sen
MBBS · DRM · DNB (Nuclear Medicine) · 30+ years in nuclear oncology
Director and Head, Department of Nuclear Medicine and Molecular Imaging, Fortis Memorial Research Institute. Visiting fellowships at Memorial Sloan Kettering Cancer Center, New York and University of Marburg, Germany. Past President, Association of Nuclear Medicine Physicians of India. Active interest in the global emerging radioligand therapy pipeline including Pb-212, Th-227 and Tb-161.
FellowshipsMSK New York · Marburg
Past PresidentANMPI
SpecialityEmerging alpha & high-LET radionuclides
Full profile
References & citations
- Delpassand ES, Tworowska I, Esfandiari R, et al. Targeted Alpha-Emitter Therapy with 212Pb-DOTAMTATE for the Treatment of Metastatic SSTR-Expressing Neuroendocrine Tumors: First-in-Humans Dose-Escalation Clinical Trial. Journal of Nuclear Medicine, 2022;63(9):1326–1333. — ACTION-1 initial dose escalation.
- Stenberg VY, Larsen RH, Ma L-W, et al. Evaluation of the PSMA-Binding Ligand 212Pb-NG001 in Multicellular Tumour Spheroid and Mouse Models of Prostate Cancer. International Journal of Molecular Sciences, 2021;22(9):4815. — preclinical Pb-212 PSMA work.
- Müller C, Vermeulen C, Köster U, et al. Alpha-PET with terbium-149: evidence and perspectives for radiotheragnostics. EJNMMI Radiopharmacy and Chemistry, 2016;1:5. — broader alpha-emitter landscape review.
- Hammer S, Hagemann UB, Zitzmann-Kolbe S, et al. Preclinical Efficacy of a PSMA-Targeted Thorium-227 Conjugate (PSMA-TTC), a Targeted Alpha Therapy for Prostate Cancer. Clinical Cancer Research, 2020;26(8):1985–1996. — Bayer thorium PSMA programme.
- Morgenstern A, Apostolidis C, Kratochwil C, et al. An Overview of Targeted Alpha Therapy with 225Actinium and 213Bismuth. Current Radiopharmaceuticals, 2018;11(3):200–208. — alpha therapy landscape review.
- Pruszyński M, Łyczko M, Bilewicz A, Majkowska-Pilip A. Astatine-211: clinical translation of targeted alpha-therapy. Cancer Biotherapy and Radiopharmaceuticals, 2023;38(6):348–363. — astatine clinical translation review.