Nuclear Medicine · Neuroendocrine tumour theranostics · 1.0

Krenning score: somatostatin receptor uptake grading

A five-grade visual scale of tumour somatostatin receptor uptake on 111In-pentetreotide scintigraphy, used historically to select patients for peptide receptor radionuclide therapy.

Purpose

To grade tumour somatostatin receptor expression visually on somatostatin receptor scintigraphy by comparing lesion uptake with normal liver and spleen/kidney, principally to judge suitability for somatostatin receptor-targeted therapy.

Grade	Visual uptake criterion	Practical interpretation
0	No uptake in the lesion	No demonstrable somatostatin receptor expression
1	Very low uptake, below normal liver	Receptor expression present but insufficient for receptor-targeted therapy
2	Uptake equal to or less than normal liver	Threshold grade used for eligibility in the NETTER-1 trial
3	Uptake greater than normal liver	Considered adequate receptor expression for peptide receptor radionuclide therapy
4	Uptake greater than normal spleen or kidney	Highest receptor expression grade

How to use it

The score is a visual, lesion-level comparison against physiological reference organs, not a quantitative measurement; normal liver is the reference for grades 1-3 and spleen or kidney for grade 4.
It was derived from planar and SPECT imaging with 111In-pentetreotide, where physiological hepatic, splenic, renal and bowel activity limits detection of small or hepatic lesions.
NETTER-1 required tumour uptake at least equal to normal liver, corresponding to Krenning grade 2 or above, on somatostatin receptor scintigraphy for enrolment.
Uptake is heterogeneous between lesions in the same patient; a single index lesion grade may misrepresent overall disease, so discordant low-uptake lesions should be described separately.
68Ga-DOTA-peptide PET/CT has largely replaced scintigraphy and has higher lesion detection, so a Krenning grade read from PET is an extrapolation and should be reported as such alongside SUVmax and the reference organ used.

Common mistake

Applying the original grade thresholds unchanged to 68Ga-DOTATATE or 68Ga-DOTATOC PET/CT, where lesion-to-liver contrast and physiological biodistribution differ from 111In-pentetreotide scintigraphy, and then presenting the result as a validated eligibility criterion.

Exam pearl

Grades 0-3 are referenced against normal LIVER; only grade 4 is referenced against SPLEEN or KIDNEY. NETTER-1 eligibility was uptake at least equal to normal liver.

Viva questions

What does the Krenning score measure?: It is a visual five-point grading of tumour somatostatin receptor uptake on somatostatin receptor scintigraphy, comparing lesion uptake with normal liver and with spleen or kidney.
List the grades of the Krenning score.: Grade 0 no uptake; grade 1 very low uptake below liver; grade 2 uptake equal to or less than normal liver; grade 3 uptake greater than normal liver; grade 4 uptake greater than normal spleen or kidney.
Which reference organs are used, and where do they change?: Normal liver is the reference for grades 1 to 3; spleen or kidney becomes the reference only at grade 4.
How was the score used in NETTER-1?: NETTER-1 required tumour uptake at least equal to normal liver on somatostatin receptor scintigraphy, that is Krenning grade 2 or higher, as an enrolment criterion for 177Lu-DOTATATE.
Why is the score problematic when applied to 68Ga-DOTATATE PET/CT?: The scale was derived from 111In-pentetreotide planar and SPECT imaging; PET has different tracer biodistribution, resolution and lesion-to-background contrast, so grades read from PET are an extrapolation and are not a validated eligibility criterion.
What should be reported when lesions differ in uptake?: Uptake heterogeneity should be stated explicitly, with the lowest-uptake and any FDG-avid or non-expressing lesions described separately, because a single index lesion grade can overestimate suitability for receptor-targeted therapy.