A biopsy-guided VHH nanobody targeting platform that phenotypes each patient's tumor, selects the matched nanobodies from a curated library, and delivers a personalized therapy prescription. The targeting intelligence is payload-agnostic — built for radioligand therapy today, and any precision oncology payload tomorrow.
A nanobody is the smallest naturally occurring antigen-binding fragment known in biology. Discovered in 1993 in camelid blood, it is the variable domain of a heavy-chain-only antibody — a single protein domain that does the full job of a conventional antibody's two-chain binding arm, at one-tenth the size.
That size difference is not cosmetic. It fundamentally changes what's possible in cancer imaging and therapy.
Click each to compare // CDR3 loop shown in teal enables hidden epitope access
In 1993, researchers at the Vrije Universiteit Brussel discovered that camelids — llamas, camels, and dromedaries — naturally produce a unique class of antibody found nowhere else in nature: heavy-chain-only antibodies (HCAbs). Unlike conventional antibodies, these have no light chains. Their single variable domain (the VHH) does all the binding work alone — at one-tenth the size of a conventional antibody. HelioKrystos harnesses this gift — a molecular tool placed in nature long before we knew we would need it — using phage display to build an ever-expanding library of these domains against cancer targets.
Click each step to see how the HelioKrystos platform works from first sample to final prescription.
A standard core needle biopsy of the patient's tumor is obtained — the same procedure already used in clinical oncology workup. No additional invasive procedure is required beyond standard-of-care tissue sampling.
The biopsy is sent to the HelioKrystos phenotyping workflow. What returns is a molecular map: which tumor-associated antigens are expressed, and at what level.
The biopsy expression profile is matched against the HelioKrystos curated library. Nanobodies corresponding to the patient's expressed antigens — and only those — are pulled from the library for that individual.
Because the library is pre-validated, no de novo nanobody discovery is required. Selection happens in hours, not months. This is what makes the workflow clinically scalable.
The biopsy-selected nanobodies — matched to that patient's specific antigen expression profile — are radiolabeled with a PET isotope and administered for standard PET/CT imaging. Nanobody-based tracers offer rapid tumor uptake and fast blood clearance, enabling same-day imaging with low background signal and high tumor-to-background contrast.
The imaging output confirms in vivo target engagement and quantifies uptake per lesion — providing the biological basis for the therapy prescription that follows.
The quantitative PET data — antigen density per lesion, pharmacokinetic curves, organ uptake — is fed into the HelioKrystos dosimetry engine. Using absorbed dose modeling (MIRD formalism + Monte Carlo), the engine calculates the exact therapeutic activity needed to deliver a tumoricidal dose while staying within organ tolerance limits.
The same nanobody used for imaging is loaded with a therapeutic radionuclide — ¹⁷⁷Lu or ²²⁵Ac — in a personalized activity prescription unique to that patient's tumor biology.
The HelioReport is the clinical deliverable — a structured, oncologist-facing document summarizing the patient's complete tumor antigen expression profile, PET imaging findings, and a personalized therapy prescription with individualized payload and dosing guidance.
Think of it as the Foundation Medicine genomic report, but for targeted drug delivery: a molecular portrait of the tumor that directly translates into an actionable, individualized treatment plan — whether the payload is a radionuclide, a cytotoxin, or a future therapeutic.
VHH genes from immunized camelids are cloned into M13 phagemid vectors, generating libraries of 10⁸–10¹⁰ unique binders displayed on phage surface proteins. Iterative panning against recombinant tumor antigens over 3–5 rounds enriches high-affinity, radiolabeling-compatible binders with Kd values in the low nanomolar range.
Molecular BiologyRadiolabeled VHH nanobodies offer a favorable imaging profile: rapid tumor uptake driven by high-affinity binding, fast renal clearance due to the ~15 kDa size, and same-day imaging capability. These properties — well-established in the nanobody imaging literature — produce high tumor-to-background contrast and enable per-lesion quantification of target antigen engagement in vivo.
Nuclear MedicineVHH nanobodies are site-specifically conjugated via engineered C-terminal cysteine or His-tag sequences. Diagnostic labeling uses ⁶⁸Ga (NOTA chelate, t½ 68 min) or ¹⁸F (AlF-NOTA, t½ 110 min) for PET. Therapeutic loading uses ¹⁷⁷Lu (DOTA chelate, t½ 6.7 days, β⁻ emitter) or ²²⁵Ac (DOTA, t½ 9.9 days, α emitter) depending on tumor burden and histology.
RadiochemistryPatient tumor biopsy undergoes rapid IHC panel staining against the full HelioKrystos antigen library, generating a semi-quantitative expression score (H-score) per target. Proteomic validation confirms IHC findings. The resulting expression profile is the sole determinant of nanobody selection — no genomic data or prior treatment history required.
Pathology · ProteomicsThe curated VHH library spans antigens expressed across prostate (PSMA), breast and gastric (HER2), lung and colorectal (EGFR), neuroendocrine (SSTR2), and pan-cancer (CEA, CAIX) tumors. A single platform infrastructure serves multiple indications simultaneously — no lead indication required, no regulatory siloing by cancer type.
Oncology · StrategyPost-imaging dosimetry uses MIRD (Medical Internal Radiation Dose) formalism incorporating patient-specific PET-derived organ uptake and tumor pharmacokinetics. Monte Carlo simulation of radionuclide transport provides absorbed dose estimates per lesion and per organ-at-risk. Output is a patient-specific therapeutic activity in GBq — not a protocol default.
Medical PhysicsDr. Magnusson is a Nuclear Medicine physician trained at the University of Wisconsin, with direct clinical experience administering radioligand therapy including ¹⁷⁷Lu-PSMA and ¹⁷⁷Lu-DOTATATE. He founded HelioKrystos out of a straightforward conviction: patients deserve better outcomes and a better treatment experience than current protocols can offer.
HelioKrystos emerged from the clinical reality of watching cancer patients struggle with the toxicity of systemic chemotherapy. This platform provides a scaffolding for precision oncology — delivering therapy to where it's needed, sparing the rest — with the goal of better outcomes and a more positive experience for patients.
HelioKrystos is building the targeting intelligence layer for precision oncology — a payload-agnostic platform that begins with radioligand therapy and expands to nanobody-drug conjugates, immunotoxins, and beyond. We are pursuing a seed round to fund platform validation, VHH library expansion, and first-in-human imaging feasibility, and are actively engaging oncology-focused angels, life science seed funds, and strategic pharma partners.