Krenning Score on 68Ga-DOTATATE PET/CT
Tumors with Krenning scores of 2 or higher (uptake equal to or greater than liver) are eligible for peptide receptor radionuclide therapy (PRRT), though scores of 3-4 are strongly preferred for optimal treatment response. 1
Krenning Score Classification System
The Krenning score is a visual grading system applied to somatostatin receptor imaging that quantifies tumor uptake as follows:
- Score 0: No uptake 1
- Score 1: Very low/equivocal uptake 1
- Score 2: Clear but faint uptake (less than or equal to liver uptake) 1
- Score 3: Moderate uptake (higher than liver uptake) 1
- Score 4: Intense uptake 1
PRRT Eligibility Criteria Based on Krenning Score
The minimum threshold for PRRT consideration is a Krenning score ≥2, but clinical practice strongly favors scores ≥3 for treatment selection. 1, 2
Specific Requirements:
- High somatostatin receptor expression determined by 68Ga-DOTATATE PET/CT is mandatory before considering PRRT 1
- Patients must demonstrate modified Krenning score ≥3 for optimal PRRT candidacy, as evidenced by clinical trial data showing all treated patients had scores ≥3 2
- 68Ga-DOTATATE PET/CT is more sensitive than somatostatin receptor scintigraphy for determining receptor status and should be the preferred modality 1
Optimal Timing for Scoring
Quantification should be performed at 24 hours after injection or later for 111In-pentetreotide, while 68Ga-DOTATATE images are acquired 45-60 minutes post-injection. 1, 3
The recommended dose for 68Ga-DOTATATE is 2 MBq/kg body weight up to 200 MBq maximum, administered as an intravenous bolus 3
Additional PRRT Eligibility Requirements Beyond Krenning Score
Beyond adequate somatostatin receptor expression, patients must meet these criteria 1:
- Histopathology: NET proven by immunohistochemistry 1
- Performance status: Karnofsky/Lansky >60% or ECOG <2 1
- Tumor differentiation: Preferably grade 1/2 (well-differentiated) 1
- Proliferation rate: Ki-67/mitotic index ≤20% preferred 1
- Hematologic function: WBC >3,000/μl with absolute neutrophil count >1,000/μl; platelets >75,000/μl for 177Lu-DOTATATE 1
- Renal function: Adequate creatinine clearance, as kidneys are the dose-limiting organ 1
Clinical Context and Pitfalls
NCCN guidelines recommend PRRT with 177Lu-DOTATATE specifically for patients with somatostatin receptor-positive imaging AND progression on octreotide/lanreotide. 1
Important Caveats:
- Grade 3 neuroendocrine carcinomas rarely benefit from PRRT due to low somatostatin receptor expression, even if Krenning score appears adequate 1
- FDG-PET should be added for G2 NETs with Ki-67 ≥10% and all G3 NETs, as higher-grade tumors show decreased somatostatin receptor expression 3, 4
- False-positive uptake can occur in granulomatous disease, inflammatory conditions, thyroid disease, and breast lesions due to SSTR2 expression in activated lymphocytes and macrophages 1
- Discordance between Ki-67 and imaging can occur, emphasizing the need for histologic confirmation and potentially dual-tracer imaging in complex cases 5
Comparison Reference: Normal Tissue Uptake
Normal physiological uptake follows this hierarchy (highest to lowest): spleen > kidneys > adrenal glands > liver > stomach > small intestine > prostate > pancreas > thyroid > uterus 6
This reference pattern helps distinguish pathological from physiological uptake when applying the Krenning score.