Y-90 FAPI therapy in India — investigational radioligand therapy for FAPI-positive solid tumours.

What is FAPI therapy?

FAPI is one of the most active research areas in nuclear oncology because Fibroblast Activation Protein is, in effect, a pan-cancer target. It is expressed in the cancer-associated fibroblasts of most epithelial cancers (pancreatic, gastric, oesophageal, biliary, colorectal, breast, lung, ovarian, head and neck) and in many sarcomas, with low expression in healthy adult tissues except healing wounds and a few normal sites.⁴ That makes one tracer-and-therapy system potentially useful across many tumour histologies — the same Ga-68 FAPI PET that finds the disease maps where a Y-90 or Lu-177 FAPI therapy could deliver dose.

Clinical experience is still early. The published evidence is composed of compassionate-use case series, mostly from German and Indian academic centres, and a handful of phase 1 / phase 2 protocols. There are no completed phase 3 trials. At Theranostic Physicians, Y-90 FAPI is offered to a small, carefully selected group of patients each year, through a multidisciplinary review process that begins with a Ga-68 FAPI PET scan and ends with an individualised, written treatment plan.

How Y-90 FAPI works.

The mechanism rests on a simple but powerful biological observation: cancers are not just tumour cells. Around the malignant cells sits a dense network of cancer-associated fibroblasts (CAFs) that build the tumour's supporting stroma, suppress immune attack, and remodel the surrounding tissue. These fibroblasts strongly express a cell-surface enzyme called Fibroblast Activation Protein (FAP) — rarely seen in healthy adult tissue.⁴ The therapy exploits that biology in three steps:

• Targeting. The FAPI molecule (most commonly FAPI-46, sometimes FAPI-04 or FAP-2286) is a small inhibitor designed to bind FAP with high affinity. The same molecule, when labelled with Gallium-68, is used as the diagnostic PET tracer that maps where the target is expressed in any given patient.³⁴
• Delivery. For therapy, the FAPI molecule is chelated to Yttrium-90, a pure beta-emitting radioisotope with a physical half-life of 64.1 hours and a maximum beta energy of 2.28 MeV. The maximum tissue range is approximately 11 mm — the longest of any beta-emitter used in clinical radioligand therapy — with a mean range of about 2.5 mm.
• Cytotoxicity. Once the FAPI binds in the tumour stroma, Y-90 deposits energy through a high flux of beta particles. The long range produces a strong crossfire effect — radiation crosses many cell diameters from each binding site, treating both the targeted CAFs and the adjacent tumour cells, even where uptake is heterogeneous. The therapy is, in this sense, a stromal-targeted strategy that exploits the cancer's dependence on its supporting microenvironment.¹

The most important physics consequence is the crossfire range. Y-90 covers approximately 5× the tissue range of Lu-177, which is why Y-90 is typically preferred for bulky tumours where deeper, more uniform dose delivery matters more than precision; and why Lu-177 is preferred for smaller, microscopic disease where surrounding tissue must be spared.⁵ The choice between the two is a clinical judgement informed by dosimetry and disease distribution — not a tumour-type rule.

Who is a candidate?

Because Y-90 FAPI is investigational and the published experience is still small, eligibility is necessarily strict. The decision is multidisciplinary and built on imaging, prior treatment lines, organ function, and informed consent. The core eligibility criteria:

• Histologically confirmed solid tumour with FAPI uptake demonstrated on a recent Ga-68 FAPI PET-CT scan. The intensity and pattern of uptake matter — strong, multifocal uptake is what makes a patient a candidate; faint or absent uptake takes them out of the conversation.⁴
• Standard therapies exhausted or contraindicated. Y-90 FAPI is not a substitute for approved first-line treatment. Patients should have progressed through, become refractory to, or be unable to tolerate the chemotherapy, immunotherapy, targeted therapy and locoregional options appropriate for their cancer.
• Adequate organ function. Bone marrow (haemoglobin generally > 9 g/dL, platelets > 75 × 10⁹/L, ANC > 1.0 × 10⁹/L), liver function within reasonable limits, and creatinine clearance generally > 40 mL/min. Y-90 is renally cleared, so renal status is part of the dosimetry conversation.
• Performance status ECOG 0–2 and an estimated life expectancy of at least 3 months from the start of therapy.
• Capacity for informed consent to an investigational therapy with limited long-term evidence. The conversation about uncertainty — what we know, what we don't, and what alternatives exist — is part of the workup.

Tumour types where the published FAPI therapy experience is strongest:

• Soft-tissue and bone sarcoma — one of the earliest FAPI therapy populations, with case series from Kratochwil and others reporting clinical benefit in patients with progressing disease on standard therapy.¹⁷
• Pancreatic adenocarcinoma — a setting with few effective options after gemcitabine/nab-paclitaxel and FOLFIRINOX, where FAPI uptake is typically intense.²
• Cholangiocarcinoma (intrahepatic and extrahepatic biliary tract cancer).
• Gastric and gastro-oesophageal cancers with strong FAPI uptake.
• Refractory ovarian cancer, salivary gland cancers, hepatocellular carcinoma, certain head and neck cancers, and cancer of unknown primary (CUP) when FAPI uptake is established.

The treatment protocol.

FAPI therapy does not yet have a single regulator-approved regimen. Most published case series have used 2 to 4 cycles, 4 to 8 weeks apart, with the per-cycle activity determined by individual dosimetry rather than a fixed-dose formula. At Theranostic Physicians, every Y-90 FAPI patient receives an individualised written treatment plan after the pre-treatment workup.

Total treatment span: typically 3 to 6 months across 2 to 4 cycles. Some patients complete the planned course; others stop early for tolerability or progression; a few continue for additional cycles. Cycle decisions are case-by-case, not template-based.

Case-series evidence.

It is important to be precise about the strength of the evidence for Y-90 FAPI. There are no randomised phase 3 trials. There are no formal regulatory approvals. The published clinical evidence consists of compassionate-use case reports and small phase 1/2 case series, mostly from German academic centres in Heidelberg and Essen, with growing contributions from Indian, Turkish and other centres. What follows are the headline observations from that literature — useful for understanding what the therapy can do, but not a basis for predicting any individual patient's response.

Kratochwil et al. — the first clinical FAPI therapy report

The foundational paper that opened the field was Kratochwil and colleagues' 2019 imaging study in the Journal of Nuclear Medicine — an evaluation of 68Ga-FAPI uptake across 28 different cancer types in 80 patients, which established the pattern of strong FAPI signal in sarcoma, oesophageal, breast, cholangiocellular and lung cancers, and provided the diagnostic basis for therapeutic translation.¹ The first clinical therapeutic report followed in 2021 in EJNMMI: a single patient with progressing pulmonary metastases from soft-tissue sarcoma treated with three cycles of ¹⁵³Sm-FAPI-46 followed by one cycle of ⁹⁰Y-FAPI-46, achieving stable disease for eight months on imaging.² These reports were hypothesis-generating, not statistically powered.

Ferdinandus and Fendler — the early Y-90 case series

The largest published clinical experience with Y-90 FAPI-46 comes from the Essen group. Ferdinandus and colleagues reported in JNM 2022 on the initial nine-patient case series — six with sarcoma, three with pancreatic adenocarcinoma — all heavily pretreated and having exhausted approved therapies, with high FAPI uptake (SUVmax ≥ 10 in > 50% of lesions).⁵ Fendler and colleagues subsequently extended this experience to a 21-patient cohort published in Clinical Cancer Research 2022, predominantly sarcoma patients, demonstrating that 90Y-FAPI-46 was safe with organ doses below critical range and led to disease control in roughly one-third of patients, particularly those with sarcoma.⁷

Pancreatic and other cancers

Pancreatic ductal adenocarcinoma is one of the cancers with the densest stromal compartment and most intense Ga-68 FAPI uptake, which makes it conceptually attractive for stromal-targeted therapy. Watabe and colleagues at Osaka University demonstrated feasibility of FAPI-targeted theranostics in pancreatic xenograft mouse models using ⁶⁴Cu and ²²⁵Ac labelled FAPI-04, supporting clinical translation.⁶ Three of the nine patients in the Ferdinandus 2022 series, and additional patients in the Fendler 2022 cohort, had pancreatic adenocarcinoma. Published responses are heterogeneous, but the safety profile in this population — where chemotherapy is poorly tolerated — is one of the consistent positive observations.

Indian experience

Indian academic centres have made substantive contributions to the FAPI literature. Ballal and colleagues at AIIMS Delhi published the first-in-human biodistribution, pharmacokinetics, and dosimetry data for two clinically usable FAPI radioligand therapy compounds — [¹⁷⁷Lu]Lu-DOTA.SA.FAPi and [¹⁷⁷Lu]Lu-DOTAGA.(SA.FAPi)₂ — in 2021.⁹ Kuyumcu and colleagues at Istanbul University reported low-dose dosimetric safety data with ¹⁷⁷Lu-FAPI-04.⁸ Therapeutic FAPI in India remains concentrated in a small number of centres operating under compassionate-use protocols.

What this means for an individual patient

For a patient considering Y-90 FAPI today, the realistic frame is: this is a therapy that can produce clinically meaningful benefit in some patients, in tumour types where standard options are exhausted, and where the disease shows strong FAPI uptake. It is not a substitute for approved therapy. Outcomes are individual. The evidence is early. We discuss this candidly during the consultation; we don't oversell it.

Cost of Y-90 FAPI in India.

Because Y-90 FAPI therapy is investigational, individually dosimetry-led, and varies meaningfully by tumour distribution and cycle count, per-cycle pricing is quoted on a case-by-case basis rather than from a standard rate card. A written quote is issued after the pre-treatment evaluation and is honoured for 60 days.

International patients should expect to allocate at least 3 to 5 days in Gurugram per cycle for the work-up, infusion, post-therapy SPECT, and pre-discharge review. Many patients combine the visit with diagnostic FAPI PET work-ups for staging or restaging at the same time.

What about side effects?

The published case series of FAPI radioligand therapy describe a side-effect profile that is, in general, milder than systemic chemotherapy in heavily pretreated patients — one of the recurring positive observations across the literature.¹⁵ However, because the populations studied have been small and largely terminal-illness cohorts, the long-term safety profile is still being characterised. The findings below summarise what has been reported.

Common (reported in > 10% of patients in case series)

• Fatigue — usually mild to moderate, typically lasting 1–2 weeks after each cycle.
• Pain flare — transient worsening of pain at sites of skeletal or visceral disease in the first few days after infusion. Managed with standard analgesia and often resolves within a week. As with other bone-active radioligand therapies, a pain flare does not predict failure.
• Transient anaemia, lymphocytopenia, thrombocytopenia — mild to moderate cytopenias are common, particularly in patients with prior chemotherapy. Blood counts are mandatory before every cycle.

Uncommon (reported in some series)

• Nausea — usually mild and responsive to standard antiemetics.
• Transient liver enzyme elevation — particularly in patients with significant hepatic disease burden.
• Mild renal function changes — Y-90 is renally cleared, so kidney function is monitored carefully. Pre-treatment renal status is part of the dosimetry conversation.

Rare but important

• Significant cytopenia or bone marrow toxicity — primarily in patients with extensive prior cytotoxic therapy or marrow involvement. The risk informs cycle activity decisions.
• Long-term safety — not fully characterised. Reflects the early state of the evidence rather than a known concerning signal.

Y-90 vs Lu-177 FAPI.

FAPI therapy is delivered with one of two beta-emitting isotopes — Y-90 or Lu-177 — chelated to the same FAPI ligand. They are not interchangeable; they have meaningfully different physics, and the choice between them is one of the more nuanced decisions in FAPI radioligand therapy. They can also be sequenced in selected patients.

How we choose between them: the decision is informed by dosimetry, disease distribution and patient-specific factors — not a rule of thumb. Broadly:

• Bulky, heterogeneous-uptake disease → Y-90 FAPI is typically preferred for the longer-range crossfire.
• Smaller, multifocal, microscopic-pattern disease → Lu-177 FAPI is typically preferred for the shorter range and better post-therapy imaging.
• Mixed disease, or progression after one isotope → sequencing or alternating Y-90 and Lu-177 cycles is sometimes considered, again driven by dosimetry rather than reflex.

FAPI therapy can also be combined with or sequenced after other systemic therapies in selected patients — for example, after progression on Lu-177 PSMA in prostate cancer with stromal-heavy disease, or after standard sarcoma chemotherapy. The decision is multidisciplinary and built around the individual case.

Next available Y-90 FAPI slots.

Y-90 FAPI cycles at our centre are scheduled individually after the pre-treatment workup. Each cycle is an outpatient day — reach the centre by 9 a.m., discharged by mid-afternoon, return for the post-therapy SPECT the next day. International patients typically allocate 3 to 5 days in Gurugram per cycle. Isotope must be ordered 7 days in advance, so cycle slots close one week before each listed date.