In a rare case, 177Lu-DOTATATE (Lutathera) peptide receptor radionuclide therapy showed vigorous uptake and therapeutic response in liver metastases that appeared negative on the initial 68Ga-DOTATATE PET/CT diagnostic scan.
PET-negative → therapy-positiveLiver metastases invisible on diagnostic 68Ga-DOTATATE PET/CT showed vigorous therapeutic uptake of 177Lu-DOTATATE and achieved partial response
What the researchers found
A 73-year-old man with metastatic pancreatic neuroendocrine tumor had both PET-positive and PET-negative liver metastases on 68Ga-DOTATATE PET/CT. Biopsy of a PET-negative lesion confirmed well-differentiated (G2) metastasis with high somatostatin receptor expression, indicating the scan had produced a false-negative result.
After initiating peptide receptor radionuclide therapy with 177Lu-DOTATATE (Lutathera), post-therapeutic scintigraphy revealed vigorous uptake of the therapeutic peptide even in the previously PET-negative liver metastases. Follow-up PET/CT demonstrated partial response to therapy across the treated lesions.
Why it matters
In standard practice, a negative PET scan for a specific lesion often means that lesion won't be targeted by therapy. This case challenges that assumption — showing that some PET-negative tumors can still respond to peptide receptor therapy. This has important implications for treatment decisions, as some patients with mixed PET-positive and PET-negative disease might benefit from PRRT even when not all metastases are visible on diagnostic imaging.
How the study worked
This is a clinical case report of a single 73-year-old male patient. The diagnostic workup included 68Ga-DOTATATE PET/CT, which identified both positive and negative liver lesions along with extrahepatic metastases. Histopathological biopsy of a PET-negative lesion was performed to rule out secondary malignancy. After confirming neuroendocrine origin with high somatostatin receptor expression, 177Lu-DOTATATE therapy was initiated with close monitoring of PET-negative lesions via post-therapeutic scintigraphy and follow-up PET/CT.
What this study cannot tell us
This is a single case report, which represents the lowest level of clinical evidence. The findings may not be generalizable to other patients or tumor types. The reason for the discordance between diagnostic PET (negative) and therapeutic uptake (positive) is not fully explained. Quantitative uptake values were not reported. Long-term survival outcomes were not described.
How to read the evidence
This is a single case report — the lowest tier of clinical evidence. While the observation is novel and clinically interesting, it cannot establish general principles about PET-negative tumor response to PRRT. Larger studies would be needed to determine how commonly this phenomenon occurs.
When this study was published
Published in 2023, this case report is recent and relevant to current PRRT practice. As Lutathera use expands, understanding diagnostic-therapeutic discordance becomes increasingly important.
The bigger picture
Peptide receptor radionuclide therapy is one of the most important advances in neuroendocrine tumor treatment. The standard treatment paradigm relies on diagnostic PET scans to select eligible patients and predict which lesions will respond. This case report reveals a potential gap in that paradigm — false-negative PET scans could lead to undertreating patients who might actually benefit. It raises questions about whether biopsy confirmation should play a larger role in treatment decisions when PET results are discordant.
Questions still open
- How common are false-negative 68Ga-DOTATATE PET/CT results in neuroendocrine tumor liver metastases?
- Should patients with PET-negative but biopsy-confirmed somatostatin receptor-positive tumors routinely receive PRRT?
- What biological factors cause some somatostatin receptor-positive tumors to appear PET-negative on diagnostic scans?
Common questions
What is Lutathera and how does it work?
Why is it surprising that PET-negative tumors responded to therapy?
Read the original research
177 Lu-DOTATATE (Lutathera) Therapy in 68 Ga-DOTATATE PET/CT-Negative Liver Metastases of a Neuroendocrine Tumor.
Clinical nuclear medicine, 48(12), e585-e587
Citation
Ventura, David; Roll, Wolfgang; Kasper, Hans-Udo; Rahbar, Kambiz; Stegger, Lars. (2023). 177 Lu-DOTATATE (Lutathera) Therapy in 68 Ga-DOTATATE PET/CT-Negative Liver Metastases of a Neuroendocrine Tumor.. Clinical nuclear medicine, 48(12), e585-e587. https://doi.org/10.1097/RLU.0000000000004888