ESMO25: Perspective on ‘inside-out oncology’ and targeted alpha radiotherapeutics
Radiopharmaceuticals were one of the most animated threads running through the 50th ESMO Congress in Berlin this year. Among the companies drawing sustained attention was Perspective Therapeutics, which is advancing image‑guided, targeted alpha‑particle therapies (TATs) designed to deliver the alpha‑emitting isotope lead‑212 (²¹²Pb) directly to tumours – while using matched imaging agents to personalise and monitor treatment (“theranostics”).
In 2025, the company released new interim data, cleared a regulatory “concrete ceiling” on kidney dose limits in its NETs programme, and expanded clinical activity across multiple assets. This feature distills the year’s developments, including with benefit of a conversation on the ground at ESMO 2025 with Perspective’s president and CEO Thijs Spoor, and considers how radiotherapeutics may reshape oncology in 2026 and beyond.
NETs, receptors, and the case for precision radiation
Neuroendocrine tumours (NETs) arise in hormone‑secreting glands throughout the body.
“Neuroendocrine tumours are tumours that arise in various glands throughout the body […] When patients are symptomatic, they feel really gross [with] flushing, diarrhoea, and general malaise,” explained Spoor.
Patients are often stabilised for years on somatostatin analogues; however, progression eventually necessitates disease‑controlling therapy. Clinically, the somatostatin receptor subtype 2 (SSTR2) presents as an overexpressed target on many NETs, enabling elegant PET imaging and receptor‑directed therapy.
Spoor underscored at ESMO that quality of life and preservation of systemic health become paramount in NETs, precisely because patients may live for decades with the underlying disease. That reality sets a high bar for safety as well as efficacy, especially for potent alpha emitters.
Perspective Therapeutics’ approach leans into image‑guided dosimetry and biodistribution optimisation: iterating compounds in animal models to minimise off‑target organ retention (notably kidneys and liver), validating efficacy preclinically, then imaging in humans over 24 hours to anticipate tissue exposure before treatment. The company’s proprietary chelator technology is central to that strategy and underpins all clinical and preclinical programmes.
VMT‑α‑NET (²¹²Pb): From ASCO safety momentum to ESMO efficacy expectations
Perspective is conducting a multi‑centre, open‑label Phase 1/2a dose‑escalation/expansion trial of [²¹²Pb]VMT‑α‑NET in unresectable or metastatic SSTR2‑positive NETs (NCT05636618). Key milestones this year have included:
- ASCO‑GI Jan 2025: Early cohorts (2.5 mCi and 5.0 mCi) showed no dose‑limiting toxicities and initial responses.
- ASCO May 2025: Data cut-off 30th April 2025; 42 patients treated, no grade 4/5 adverse events, ORR ~57% in Cohort 2, seven of nine evaluable patients progression‑free beyond one year.
- FDA 21st June 2025: Authorised escalation to 6 mCi, breaking the historical ~23 Gy renal cap by 20% based on robust dosimetry and safety.
- ESMO 20th October 2025: Data cutoff 12th September 2025; 55 patients across cohorts, ORR 44% in Cohort 2, 80% progression‑free at ≥9 months, no renal complications or clinically significant myelosuppression.
“What was exciting for the patients in our study is that we showed a 57% response rate,” said Spoor back at ASCO 2025. “Physicians love that profile, and so, to get a better safety profile and a better efficacy response, it’s really exciting for patients.”
These results reinforce the potential for alpha therapies to outperform beta‑based predecessors like Lutathera (Lu‑177‑DOTATATE, ~13% ORR historically) while maintaining a favourable safety profile.
“Because these particles are so potent, you have to be very careful about safety,” explained Spoor. “[And] make sure all the radioactive particles are going to the tumour and not to other areas of the body. Alpha particles are so much more destructive than betas – a double-edged sword. We have the obligation to really protect healthy tissue from exposure.”
Beyond NETs, Perspective also advanced [²¹²Pb]VMT01 (targeting MC1R) in metastatic melanoma:
- March 2025: First patient dosed at 1.5 mCi in combination with nivolumab.
- April 2025: Monotherapy cohort (1.5 mCi) reopened, including patients with brain metastases.
- September 2025: First patient dosed at 3.0 mCi in combination with nivolumab; 3.0 mCi monotherapy cohort reopened after positive safety review.
Breaking the radiopharma “concrete ceiling”: Regulatory context
Spoor’s ESMO remarks framed the FDA’s 2025 draft guidance on Oncology Therapeutic Radiopharmaceuticals: Dosage Optimization During Clinical Development and the EMA’s 2024 concept paper as complementary but not identical paths that industry must navigate – differences persist in expectations for long‑term safety follow‑up, the weight of dosimetry vs clinical toxicity, and trial design details. Nevertheless, the FDA’s willingness to permit higher renal doses – grounded in clinical imaging and dosimetry – was a watershed moment for the field.
“The FDA gave us the go-ahead to increase to a 6 mCi dose,” Spoor said. “[Thereby] breaking a concrete ceiling in the radiopharmaceutical field.”
“We have enabling technology for isotope production at very high volume and a platform that develops what we think are safer medicines,” he continued. “Radiopharmaceuticals are emerging as the next pillar in oncology… targeting cancers from the inside out.”
Spoor pointed to the rapid transition from “potential” to “presence” for multiple isotopes and companies as key to these developments, arguing that radiopharmaceuticals are emerging as the next pillar in oncology, alongside targeted chemotherapy (ADCs) and immuno‑oncology. He envisages targeted radiation from the inside‑out, pairing with targeted chemo and immune activation, each with distinct mechanisms and toxicity profiles, to “gang up” on cancer across organ systems.
The future promise of radiopharmaceuticals
Certainly, 2025 marked a turning point for Perspective Therapeutics: maturing safety data, encouraging efficacy signals, and regulatory openness to data‑driven renal dose optimisation. The company’s image‑guided, chelator‑enabled platform – coupled with ambitions in melanoma and broader solid tumours – embodies the “inside‑out” paradigm that radiopharmaceuticals promise.
As ESMO’s anniversary year looked forward to the next five decades, the near horizon feels especially proximate: in 2026, we can expect more centres capable of delivering ²¹²Pb therapies, clearer guidance convergence, and increasing exploration of alpha‑IO and alpha‑chemo combinations. If that momentum holds, radiotherapeutics may indeed cement themselves as oncology’s next pillar, expanding patient choice while raising the standard for precision, safety, and durable control.
“Anything we can throw at cancer, we should – the ability to combine targeted chemo, targeted radiation, and the immune system presents a whole new battery of precision medicine,” concluded Spoor.
About the interviewee
Thijs Spoor is president and CEO of Perspective Therapeutics.
Spoor is a healthcare executive with global experience of the healthcare industry, as well as Wall Street. Spoor possesses professional experience that crosses the medical device, biotechnology, pharmaceutical, and imaging markets, with particular experience in cardiology, oncology, and orthopaedics.
