Salivary gland toxicity has been the defining liability of PSMA-targeted radiopharmaceuticals — the reason lutetium-177 PSMA-617 carries warnings, the reason patients sometimes decline treatment, and the reason any new prostate cancer radioconjugate that sidesteps that problem deserves scrutiny rather than applause. Aktis Oncology‘s first-in-human dosimetry data for AKY-2519 show a predicted salivary gland absorbed dose of just 4.2 Gy RBE at the planned therapeutic schedule of 8 MBq × 4, compared to benchmarks from approved agents that run meaningfully higher. That single number reframes the clinical conversation around this molecule.
The dataset comes from 16 patients with metastatic castration-resistant prostate cancer evaluated at a South African nuclear medicine center, using both gallium-68 and low-dose lutetium-177 labeled versions of AKY-2519 as imaging surrogates. The design is methodologically sound: PET/CT at three time points captured early biodistribution, SPECT/CT imaging out to 144 hours enabled proper dosimetry modeling, and lutetium-177 data were used to project actinium-225 absorbed doses — the therapeutic isotope Aktis actually intends to deploy. Tumor uptake persisted for at least six days post-administration, which matters enormously for actinium-225 given its physical half-life and the need for prolonged target engagement to capitalize on its short-range, high-LET alpha emissions. Kidney dose landed at 16 Gy RBE and liver at 9.9 Gy RBE — figures that sit within ranges seen as manageable in the radioligand field, though they will demand careful monitoring as dose escalation proceeds in the Phase 1b trial.
The target itself, B7-H3, is broadly expressed across mCRPC, lung, and colorectal cancers while remaining largely absent from normal tissue — a distribution that theoretically supports the favorable dosimetry profile observed here. Critically, Aktis is enrolling both PLUVICTO-naïve and PLUVICTO-experienced patients in the mCRPC Phase 1b, which is the correct strategic move: post-lutetium PSMA patients represent a growing population with no approved radiopharmaceutical option and genuine urgency for an alternative mechanism. A separate basket trial across other B7-H3-expressing solid tumors is slated to open in the second half of 2026.
The real test arrives in 2027 when preliminary efficacy signals from the mCRPC cohort become available. Track PSA response rate in PLUVICTO-experienced patients specifically — that subgroup will determine whether AKY-2519’s dosimetry advantage translates into a genuinely differentiated clinical position or remains a technical footnote.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
