NM Physician's Notes · ¹⁷⁷Lu-PSMA-617

PSMA PET is the patient-selection decision document.

¹⁷⁷Lu-PSMA-617 only works on the lesions the PSMA PET sees. The PET scan is therefore not a screening test — it is the eligibility document. This post walks the VISION criteria, the PSMAfore line-of-therapy shift, and the organ-at-risk dose ceilings that bound the six-cycle protocol.

VISION-style eligibility (the established criteria)

Six conditions the MDT confirms before referral

Histologically confirmed prostate adenocarcinoma
Castration-resistant disease — testosterone < 50 ng/dL on ongoing androgen deprivation
Disease progression on at least one androgen-receptor-pathway inhibitor (abiraterone or enzalutamide)
At least one prior taxane (docetaxel; cabazitaxel allowed) — VISION post-taxane criterion
Ga-68 PSMA-11 PET/CT showing PSMA-positive disease in at least one target lesion (uptake greater than liver)
No PSMA-negative dominant disease (i.e. no large lesion lacking PSMA uptake)

Source: Sartor O et al. VISION trial, NEJM 2021; EANM/SNMMI procedural guidelines 2023.

The PSMAfore line-of-therapy shift

PRRT before taxane — what changes

PSMAfore eligibility removed the prior-taxane requirement — patients now considered after progression on one ARPI, before docetaxel
PSA-PFS and rPFS endpoints favoured PRRT over a second ARPI switch (HR 0.43)
Safety profile favoured PRRT over chemotherapy — relevant for older / multimorbid patients unable to tolerate docetaxel
Practical implication: more PSMA-617 candidates per year in an Indian centre, earlier in the treatment line

Source: Morris MJ et al. PSMAfore trial, Lancet 2024.

Dose-limiting organs

Per-cycle dosimetry — the organs that bound the six-cycle course

Organ / Tissue	Target	Practical implication	Source
Tumour	maximise	High SUVmean on baseline PSMA PET correlates with high tumour dose per cycle and longer rPFS / OS.	Kuo PH et al. J Nucl Med 2022.
Kidney	< 23 Gy cumulative	Renal dose constraint follows EBRT-derived tolerance. Per-cycle dosimetry tracks cumulative dose; cycle 5 / 6 stopped if approaching threshold.	EANM/SNMMI procedural guidelines 2023.
Salivary gland	< 30–40 Gy	Xerostomia is the dose-limiting late toxicity. Pre-therapy cooling, lemon-juice / vitamin-C protocols and dose-fractionation lower exposure.	Begum NJ et al. EJNMMI 2019.
Lacrimal gland	monitor	Dry-eye and meibomian-gland inflammation reported. Less dose-limiting than salivary, still tracked.	Kratochwil C et al. EJNMMI 2023.
Bone marrow	haematology	Grade 3 thrombocytopenia in ~10 % VISION patients. Monitor CBC pre each cycle, defer or reduce activity if cytopenia.	VISION supplementary appendix.

Lu-177 + PSMA-617

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Sibling posts in the ¹⁷⁷Lu-PSMA-617 family.

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Why Lu-177 purity changes mCRPC therapy

The salivary-gland dose ceiling, not tumour response, sets the six-cycle stopping criterion. Why ≥ 3,000 GBq/mg, ≥ 99.9 % RNP and ≥ 99 % RCP are what the VISION protocol chemistry actually requires.

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