Theranostics Response Criteria

Quick Answer

Response to radioligand therapy is judged with molecular-imaging frameworks specific to the target, alongside biochemical markers and conventional imaging. For PSMA therapy, RECIP 1.0 classifies response on PSMA-PET; for somatostatin-receptor disease, the Krenning score grades uptake and predicts benefit. Reporting frameworks (PROMISE / PSMA-RADS) standardize PSMA-PET interpretation.

RECIP 1.0 (Response Evaluation Criteria in PSMA PET/CT)

RECIP 1.0 was developed for mCRPC treated with PSMA radioligand therapy. It combines the change in whole-body PSMA tumor volume (PSMA-VOL) with the appearance of new lesions:

The requirement that progression need both a volume increase and new lesions reduces false calls from measurement noise. RECIP has also been adapted to quantitative Lu-177-PSMA SPECT/CT for earlier, on-treatment assessment.

Krenning Score (somatostatin-receptor uptake)

A visual grading of tumor uptake on somatostatin-receptor imaging relative to reference tissues, used to select patients for and assess PRRT:

Scores 3–4 indicate sufficient receptor expression to expect benefit from ¹⁷⁷Lu-DOTATATE. (The score was originally described for ¹¹¹In-octreotide and is applied analogously to Ga-68/Cu-64-DOTATATE PET.)

PROMISE / PSMA-RADS (reporting frameworks)

Standardized frameworks for reading and reporting PSMA-PET: they define a molecular imaging TNM (miTNM) and standardized expression/uptake levels (PROMISE), and a structured level-of-certainty scoring for lesions (PSMA-RADS). Their purpose is consistent, reproducible reporting across readers and studies — essential when imaging is the gatekeeper for therapy.

Biochemical & clinical markers

• Prostate cancer: PSA trend (with molecular-imaging response for Lu-PSMA). Note PSA is not reliable for Ra-223, which targets the bone microenvironment — use alkaline phosphatase and skeletal/clinical endpoints.
• Neuroendocrine tumors: chromogranin A and symptom/hormonal control.

Match the framework to the target

Response in radioligand therapy is judged with target-specific frameworks, not RECIST alone: RECIP 1.0 for PSMA (whole-body PSMA tumor volume change + new lesions), the Krenning score for somatostatin-receptor disease, and standardized reporting (PROMISE / PSMA-RADS) for consistent PSMA-PET reads. Applying anatomic-only criteria understates molecular response and misses target-specific change.

The new-lesion rule guards against noise

RECIP requires progression to show both a volume increase and new lesions — the new-lesion requirement prevents measurement noise from being over-called as progression. Biochemical and molecular responses can diverge (e.g. PSA vs imaging); interpret them together, and hold technique/reference regions constant across serial scans.

High-Yield Pearls

• Molecular-imaging response and biochemical response can diverge; interpret them together, not in isolation.
• Use the same imaging agent, technique, and reference regions across serial studies for valid comparison.

Common Pitfalls

• Applying RECIST alone to theranostics understates molecular response and misses PSMA/SSTR-specific changes.
• Ignoring new lesions when tumor volume appears to fall — new-lesion appearance is central to progression calls.

Self-Check

Key References

• Gafita A, et al. Response Evaluation Criteria in PSMA PET/CT (RECIP 1.0). Radiology. 2023.
• Krenning EP, et al. Somatostatin-receptor scintigraphy uptake grading.
• Eiber M, et al. PROMISE / PSMA-RADS frameworks for PSMA-PET reporting.