Radiolabelled receptor-binding somatostatin analogues and their use in the imaging and radionuclide therapy of neuroendocrine tumours provides one of the few examples of functional imaging that acquires diagnostic images and delivers therapeutic radiation simultaneously, according to Dr. Luigi Aloj, a consultant in nuclear medicine at the University of Cambridge School of Clinical Medicine, U.K.
“They are one of the few theranostic agents to be approved by regulators,” he told ECR Today.
FDG PET/CT still constitutes the bulk of all PET/CT imaging in cancer, but there are areas where new radiolabelled PET tracers are being applied, some of which have now reached significant validation and in some facilities are being performed routinely to characterise, stage, monitor, and plan treatment. One example of the application of these new radiolabelled PET tracers is in imaging somatostatin receptor overexpressing gastroenteropancreatic tumours, typically of the small bowel and pancreas.
PET tracers based on somatostatin analogues are capable of binding somatostatin receptors with high affinity, providing highly sensitive PET/CT imaging with low background noise, Aloj explained. In this way, information on the level of expression of these receptors in a tumour is obtained that allows detection of disease and identification of areas of disease spread.
“When tumours demonstrate high-level somatostatin receptor expression, the same agents can be radiolabelled with nuclides that can deliver high levels of radiation to these tumours, thus providing therapeutic effects, and this approach has been validated,” he remarked.
By providing information on tumour biology and on whether the tumour is likely to respond to this type of treatment, it shows how functional imaging can be utilised to guide targeted therapy.
“This is, in general, not achievable through more anatomical imaging modalities we are accustomed to, and it provides a very elegant example of how imaging to characterise disease can be used to select candidates for treatment,” Aloj continued. “There is good evidence based on a recent large clinical trial that this treatment is effective in this particular patient group, and this type of imaging certainly contributes to accurate patient selection and the identification of candidates that are likely to benefit.”
He illustrated the potential of this approach with the case of a 33-year-old woman with insulinoma, a neuroendocrine tumour arising from pancreatic islet cells. When this patient was referred to Cambridge, she required continuous feeding to control episodes of hypoglycaemia caused by the tumours in her body that were secreting high levels of insulin. The whole-body PET/CT studies performed with Ga-68 dotatate, the gallium-68 labelled somatostatin analogue, identified multiple tumour deposits (see the maximum intensity projection [MIP] image on the left of the figure). Exemplary metastases in the liver and in an abdominal lymph node are shown in the centre panel.
The patient was treated with four cycles of lutetium-177 labelled dotatate (Lu-177 dotatate). The images in the right panel, obtained following the first cycle of treatment, show the concentration of the therapeutic agent in the known tumour lesions, indicating that high levels of therapeutic radiation were being delivered.
“Following the four cycles of treatment, the patient showed stabilisation of disease progression and marked improvement of symptoms – namely, complete control of the hypoglycaemic episodes, which allowed her to lead a normal life for nearly two years after the initial treatment at which time symptoms recurred,” he reported.
At this session on hybrid imaging beyond FDG PET/CT, Aloj will be joined by Dr. Albert Flotats, associate professor of nuclear medicine at Hospital de la Santa Creu I Sant Pau, Barcelona, Spain, who will guide ECR delegates through the use of hybrid techniques in cardiovascular imaging.
Improved methods of diagnosing and treating cardiovascular disease are needed, he said. Given that vulnerable plaque ruptures are clinically silent, the focus has shifted from atherosclerotic imaging of the individual plaque to the patient, and from invasive to non-invasive imaging modalities that facilitate comprehensive assessments of plaque characteristics and disease activity across the coronary vasculature. Despite still being limited in use, hybrid cardiovascular imaging (hybrid PET and SPECT) is at the frontier of clinical research in this field, he added.
“The combination of high signal sensitivity, within the picomolar range, of SPECT and PET for physiopathological processes, along with the high spatial resolution of CT and MRI, provides incremental information that is more than the sum of its parts,” said Flotats, who noted that examples of clinical use of this type of imaging include plaque morpho-biology burden imaging in atherosclerosis and functionally significant obstructive coronary artery disease imaging.
Asked to explain some of the key differences between hybrid PET/SPECT imaging and other modalities for cardiovascular imaging, he pointed out that hybrid PET/SPECT imaging provided highly sensitive, non-invasive, morpho-functional imaging.
Describing the role of hybrid PET/SPECT cardiovascular imaging within clinical care, he said that the technique was increasingly being used in the diagnostic approach of patients with ischaemic heart disease. “The combination of functional imaging with morphological information on the presence, extent, and severity of the disease can facilitate patient risk stratification and management,” he commented.
Also speaking will be Prof. Clemens C. Cyran from the Ludwig-Maximilians-University in Munich, Germany, and Dr. Umar Mahmood from Massachusetts General Hospital, Boston, U.S.
Special Focus Session
SF 9a Hybrid imaging: beyond FDG PET/CT
- Prostate specific membrane antigen (PSMA) hybrid imaging in guiding prostate cancer therapy
Clemens C. Cyran; Munich/DE - Somatostatin receptor imaging and therapy
Luigi Aloj; Cambridge/UK - Hybrid PET and SPECT for cardiovascular imaging
Albert Flotats; Barcelona/ES - Imaging to guide immuno-oncology
Umar Mahmood; Charlestown, MA/US
FURTHER READING
Janssen JC, Meißner S, Woythal N et al (2018) Comparison of hybrid 68Ga-PSMA-PET/CT and 99mTc-DPD-SPECT/CT for the detection of bone metastases in prostate cancer patients: Additional value of morphologic information from low dose CT. Eur Radiol. 28(2):610-619: european-radiology.org/4994
Domachevsky L, Bernstine H, Goldberg N, Nidam M, Catalano OA, Groshar D (2019) Comparison between pelvic PSMA-PET/MR and whole-body PSMA-PET/CT for the initial evaluation of prostate cancer: a proof of concept study. Eur Radiol. doi: 10.1007/s00330-019-06353-y: european-radiology.org/6353
Grigoryan M (2018) Radiotracers in hybrid imaging. Review. ECR 2018 / C-0738: myESR.org/18738
Sit C, Amlani A, Muthuswamy K, Tang CSW, Bomanji J (2019) Pictorial Atlas: PET Tracers & PET-CT in Prostate Cancer. ECR 2019 / C-2803: myESR.org/192803
Mochula A, Zavadovsky KW, Andreev S, Lishmanov Y (2019) Coronary flow reserve assessment in patients with multivessel coronary artery disease using dynamic SPECT. ECR 2019 / C-2725: myESR.org/192725