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May 19 2014

Beware of Ga68 PET/CT False Positives in the Pancreas

Ga68 PET/CT is widely recognised as the best imaging modality for detecting indolent neuroendocrine tumors in whole body scans. However there is a significant risk of false positives in the region of the ulcinate process, also known as ‘head of the pancreas’. Any Ga68 PET/CT which leads to suspicion of a tumor in the head of the pancreas should be compared with other imaging modalities such as MRI. If a tumor is still suspected, it should be corelated with an endoscopic ultrasound (EUS) and Fine Needle Aspiration (FNA) biopsy. These counter-checks should certainly be done before deciding on any invasive procedure such as a Whipple surgery. Article (400 words) The Ga 68 PET/CT (called ‘Gallium 68 scan’) is a combined functional and anatomical imaging technique for indolent neuroendocrine tumors. This technique offers much better resolution than other types of scans and has the added benefit of producing a measurable indication of the density of SST receptors. The SST receptor density (called ‘uptake’) is an accurate predictor of whether a particular patient is a suitable candidate for Peptide Receptor RadioTherapy (PRRT). Plus, receptor density can be used to monitor the success of any treatments the patient may be receiving, including PRRT. In centers which offer the Gallium 68 scan, it has replaced Octreoscan because of the better resolution. And it is more convenient for patients and nuclear medicine staff, since everything can be done during a single visit. For the above-mentioned reasons, the Gallium 68 scan has been described as the ‘gold standard’ of imaging neuroendocrine tumors. However there is reason to be cautious when interpreting the results of a Gallium 68 scan which shows uptake in the pancreas. There can be false positives due to physiological uptake in the head of the pancreas, as described in several medical studies (eg- http://www.ncbi.nlm.nih.gov/pubmed/21571796, http://www.ncbi.nlm.nih.gov/pubmed/22157030, http://www.ncbi.nlm.nih.gov/pubmed/21792572). This occurs because of the high concentration of SST receptors in the pancreatic islet cells, resulting in physiological uptake of the somatostatin analog (ie- DOTATOC or DOTANOC). One paper concludes: “Uptake in the head of the pancreas is a common finding in patients undergoing Ga68-DOTATOC PET/CT. However, this finding most likely represents a physiological condition, especially if the uptake in the pancreatic head is similar to uptake in the liver. Therefore, quantification is recommended to avoid false-positive diagnosis.” Another concludes: “Pancreatic DOTANOC uptake must be interpreted with caution, and further studies are required.” The possibility of Gallium scan false positives in the head of the pancreas has been recognised in Europe since about 2007. It is has been reported that up to 70% of such scans may display physiological uptake “sufficiently intense to be interpreted as pathologic and simulating a tumor” (http://www.ncbi.nlm.nih.gov/pubmed/22391705). But the potential for mis-diagnosis should be of particular concern in the USA, where a few medical centers have begun to offer this imaging modality after this technique was given orphan drug designation by the FDA (http://interactive.snm.org/index.cfm?PageID=13165). In Singapore there is a court trial underway brought by a patient who was suspected of having a pancreatic neuroendocrine tumor, and who underwent a Whipple resection, only to learn that no malignancy was found. The patient is Clement Hii, a businessman from Malaysia (see image below). The surgeon had proceeded with the Whipple operation on the basis of a positive Ga68 PET/CT even while the CT and MRI were negative and no blood markers were elevated. This took place in 2010, when the physiological uptake of Ga68 DOTANOC PET/CT in the pancreas was not well understood, and centers in Asia were just starting to use the scan. So patients should undergo a Ga68 PET/CT should not rely solely on apparent uptake in the head of the pancreas as evidence of disease there. They should get an endoscopic ultrasound and other diagnostics, including a biopsy if possible, to confirm a lesion before considering a radical surgery such as a Whipple resection.