CXCR4 imaging instead of adrenal vein sampling
A common and curable cause of high blood pressure is almost never cured, because finding out which adrenal gland is at fault needs an invasive procedure few hospitals do well. A PET scan can answer the same question, and one is now heading into a registrational trial.
Overview
Primary aldosteronism accounts for 5 to 14% of all hypertension and 20 to 25% of treatment-resistant hypertension, and it can be cured by removing one adrenal gland if the excess comes from one side. Establishing which side requires adrenal vein sampling, an invasive procedure that the MATCH investigators describe as requiring a day off work, causing severe pain and hospitalisation in 1 to 3% of patients, available with a success rate above 50% in few hospitals. The consequence they report is stark: fewer than 1% of patients with primary aldosteronism are identified and fully investigated.
This is not a radiopharmaceutical looking for a use. It is the clearest standalone diagnostic case outside oncology, and it is already being built. 68Ga-PentixaFor from Pentixapharm holds EMA PRIME status granted in October 2024 and FDA Fast Track designation granted in July 2026, with an IND cleared and a phase 3 trial, PANDA, planned at approximately 270 patients in the United States. The academic evidence behind it is substantial: in a 100-patient prospective study, PET/CT agreed with adrenal vein sampling in 90% of patients against 54% for conventional CT, and a meta-analysis of seven studies covering 603 patients has been reported at pooled sensitivity 80% and specificity 91%.
The agent is also validated against pathology rather than just against another test: consistency between PET uptake and CXCR4 staining was 92.9%, and all 43 CYP11B2-positive functional nodules in one series were CXCR4-positive. What makes this record worth carrying is not that anything is missing, but that it is the field's best worked example of what an unmet-need-first opportunity looks like when it succeeds.
A curable cause of hypertension goes untreated because the test that decides who can be cured is invasive, painful, available in few centres and therefore almost never done: fewer than 1% of patients with primary aldosteronism are fully investigated.
- Single-centre concordance of 90% may not survive a multicentre phase 3 with central reading.
- The indication sits with endocrinologists and hypertension specialists who do not routinely order PET, so adoption is a referral-pathway problem as much as an accuracy one.
- The chemical series is exclusively licensed, so this is a record to learn the method from rather than an opening to enter.
- Registration of PANDA on ClinicalTrials.gov and its first patient enrolled, expected in the second half of 2026 per the sponsor.
- The Chongqing randomised trial, which is the only design that tests whether PET-guided treatment produces the same cures as sampling-guided treatment.
- Whether guideline bodies begin to name molecular imaging as an alternative to adrenal vein sampling.
The five domains of a radiopharmaceutical due-diligence review, adapted from the Fryback-Thornbury hierarchy of diagnostic efficacy. Each carries the state of the public evidence and the fact behind it, not a score out of five: a single total hides the reason and stops telling candidates apart. Domains marked as carrying most weight are the ones that decide the case at this asset's stage.
All 43 CYP11B2-positive functional nodules in one series were CXCR4-positive, and consistency between PET uptake and CXCR4 staining was 92.9%, tying the imaging signal directly to the enzyme that makes aldosterone.
Multiple completed prospective studies including 100 patients against adrenal vein sampling, 120 patients with pathology correlation, and a randomised 320-patient trial recruiting in China; an approximately 270-patient US phase 3 is planned.
PET/CT agreed with adrenal vein sampling in 90 of 100 patients against 54 of 100 for conventional CT; a reported meta-analysis of seven studies and 603 patients gives pooled sensitivity 80% and specificity 91% with an AUC of 0.91.
Effective dose from 150 MBq of 68Ga-pentixafor is 2.3 mSv, with the highest organ dose in the bladder wall at 12.2 mGy; a 2025 dosimetry paper reports 1.65 plus or minus 0.06 mSv for the same activity, both far below the 7 mSv of a standard FDG scan.
EMA PRIME and FDA Fast Track are both granted for this exact indication, the IND has cleared, and written FDA minutes reportedly identified no major concerns with the phase 3 design.
Red, amber or green on each review category, each with its reason, so an obvious no-go takes seconds rather than a meeting.
Gallium-68 small-molecule ligand, same-day imaging, effective dose around 2 mSv, and pathology-validated uptake.
A curable disease in 5 to 14% of all hypertension where fewer than 1% of patients are fully investigated because the deciding test is invasive.
The ligand was patented at the University of Würzburg and exclusively licensed to Pentixapharm in 2019, so the lead chemical series is not available.
Purely standalone: the scan replaces a procedure and depends on no drug approval, which is the strongest commercial structure a diagnostic can have.
Gallium-68 from a generator; no supply constraint.
One sponsor holds PRIME, Fast Track and a cleared IND in this indication, and the metomidate tracers are an established academic alternative; a new entrant would be third at best.
- Pentixapharm Holding AGphase 3 planned
68Ga-PentixaFor: EMA PRIME, FDA Fast Track, IND cleared, phase 3 PANDA planned at approximately 270 patients, US launch targeted 2030.
https://www.pentixapharm.com/news/ema-grants-prime-status-to-pentixapharms-lead-candidate-pentixafor - National Cancer Institute and NIDDKphase 2 recruiting
Investigator-initiated phase 2 of 68Ga-PentixaFor in hyperaldosteronism and hypercortisolism, 80 patients estimated.
https://clinicaltrials.gov/study/NCT06246357 - First Affiliated Hospital of Chongqing Medical Universityrecruiting
Multicentre randomised trial of PET/CT-guided against adrenal-vein-sampling-guided treatment, 320 participants estimated.
https://classic.clinicaltrials.gov/ct2/show/NCT06238232 - UK academic consortium (Barts, Cambridge, Guy's)published
[11C]metomidate and [18F]CETO, the non-CXCR4 precedent: molecular imaging reported non-inferior to adrenal vein sampling in MATCH, 146 patients.
https://www.nature.com/articles/s41591-022-02114-5
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