Sameer Khan

What can gallium-68 PET add to receptor and molecular imaging?

In the last decade there has been a significant increase in the development of radiolabelled peptides for diagnostic applications, especially due to simplified methods of purification. Peptides have fast clearance, rapid tissue penetration, and low antigenicity and can therefore be produced easily and inexpensively. In addition, if the diagnostic scan is positive, the peptides can be labelled with therapeutic radionuclides (yttrium-90, lutetium-177) and used for therapy [1]. Most efforts at labelling peptides have targeted somatostatin and its receptors. Somatostatin is a regulatory peptide widely distributed in the human body. Its action is mediated by membrane-bound receptors (SSTR) that are present in normal human tissues, such as thyroid, brain, gastrointestinal tract (GIT), pancreas, spleen and kidney [2]. They are also abundant in a variety of human tumours, notably neuroendocrine tumours (NET) [3] of which carcinoid tumour and phaeochromocytoma are encountered most in clinical practice. SSTR are also expressed, with variable abundance, in renal cell carcinoma, small cell lung cancer, breast cancer, prostate cancer and malignant lymphoma [4]. Somatostatin itself has a short half-life and is rapidly degraded by enzymes; therefore analogues have been developed which mimic its effects but are resistant to enzyme degradation. There are 5 somatostatin receptor subtypes but only subtypes 2 (SSTR2) and 5 (SSTR5) and to a lesser extent receptor subtype 3 (SSTR3) have a high affinity for commercially available synthetic analogues and even these differ in their affinity for the various receptor subtypes [5].

Clinical indications for Gallium-68 positron emission tomography imaging.

BACKGROUND (68)Ga-PET imaging is showing slow but steady progress when compared to (18)F-FDG PET. The advantage of in-house preparation of (68)Ga without necessity of a cyclotron, and the new generator configuration with future possibility of freeze-dried kits would make it a promising PET agent for the future. METHODS An exhaustive literature exploration was performed using the search engines High-Wire Press, Pubmed, Embase and library databases. Recent reviews on the subject and up-to-date studies on the topic were found that described the role of (68)Ga-PET imaging. Clinical experiences, including our own are described. RESULTS Recent resurgence in development of peptides labelled with radiometals, for diagnostic and therapeutic purposes, resulted in a new beginning for (68)Ga-PET imaging. Pre-clinical experience employing animal models and investigation of tracer kinetics/tumour uptake measurements using dynamic (68)Ga-PET have provided data regarding identification of Somatostatin receptors subtypes on many tumours. Present published experiences including our own support these and highlight current clinical utility of (68)Ga-PET imaging. (68)Ga-DOTATOC and (68)Ga-DOTANOC are the most prominent radiopharmaceuticals used nowadays. CONCLUSION (68)Ga-PET is employed in the management of neuroendocrine tumours and neural crest tumours (phaeochromocytoma and paraganglioma) with diagnostic and therapeutic implications where it compliments present radiologic and scintigraphic procedures. Diagnosis and radiotherapy treatment planning for meningiomas in pertinent clinical setting is another potential use of (68)Ga-PET. Limited studies have shown its utility in prostate cancer but further studies are contemplated. Therefore, current experience tends to open a new horizon for the clinical utility of (68)Ga-PET imaging in future.

Selective Internal Radiation Therapy with Yttrium-90 for Unresectable Liver Tumours

Primary and secondary liver tumours are common malignancies that are being treated more aggressively nowadays than decades ago. Surgery is the most effective method of treatment but is only suitable for a minority of patients with well-defined and easily accessible tumours. Surgical resection is contraindicated in patients with massive involvement of the liver or in cases where the disease involves the confluence of vessels at the porta hepatis. These patients may benefit from a variety of ablative and embolic therapies including selective internal radiation therapy (SIRT) with Yttrium-90 microspheres. SIRT has been introduced in the 1980s but the technology has been refined and made more available only recently. The microspheres are injected directly into the hepatic arteries, through a trans-femoral angiographic approach, and are delivered selectively to tumours due to their preferential blood supply by hepatic arteries. SIRT can therefore target small volumes disease with a higher dose of radiation compared with external-beam radiation and is associated the relatively low toxicity and a good response irrespective of tumor origin. Assessment of response to therapy is best performed with metabolic imaging using (18)F-FDG PET scanning. Although it is not considered as a cure, it has been shown to improve quality of life and prolong survival, with the main cause of death being extra-hepatic spread. The technical and clinical demands of patient selection, treatment planning, administration, and clinical follow-up require an interdisciplinary team willing to work cooperatively to achieve the best result for the patient.

Thyroid Lymphoma Incidentally Detected by 18F-Fluorocholine (FCH) PET/CT:

A 63-year-old man underwent a (18)F-fluorocholine ((18)F-FCH) PET/CT for staging assessment of a high-risk locally advanced prostate cancer with an equivocal node on conventional workup (Gleason 4 + 5, PSA 11.1; T3b, N(0/1), M(0) on standard staging investigations). (18)F-FCH-avid disease was demonstrated in the prostate and several non-enlarged pelvic nodes. An incidental focus of tracer uptake was reported within the left lobe of the thyroid gland, with subtle enlargement of the left thyroid lobe on the CT component of the study. A diagnosis of diffuse large B-cell lymphoma was confirmed following thyroid ultrasound and cytology.

FDG PET/CT Pitfalls in Gynecologic and Genitourinary Oncologic Imaging

The role of whole-body positron emission tomography (PET)/computed tomography (CT) with fluorodeoxyglucose ( FDG fluorodeoxyglucose ) is now established in the assessment of many gynecologic and genitourinary malignant tumors. FDG fluorodeoxyglucose PET/CT has been widely adopted for staging assessments in patients with suspected advanced disease, in cases of suspected disease recurrence, and for determining prognosis in a number of malignancies. A number of pitfalls are commonly encountered when reviewing FDG fluorodeoxyglucose PET/CT scans in gynecologic and genitourinary cases; these pitfalls can be classified into those that yield potential false-positive or false-negative results. Potential false positives include physiologic uptake of FDG fluorodeoxyglucose by the endometrium and ovaries in premenopausal patients, physiologic renal excretion of FDG fluorodeoxyglucose into the ureters and the urinary bladder, and increased FDG fluorodeoxyglucose activity in benign conditions such as uterine fibroids, pelvic inflammatory disease, and benign endometriotic cysts. Potential false negatives include low-level FDG fluorodeoxyglucose uptake by necrotic, mucinous, cystic, or low-grade tumors and the masking of serosal and peritoneal disease by adjacent physiologic bowel or bladder activity. In addition, there are inherent technical limitations-such as motion artifact (from respiratory motion and bowel peristalsis) and the limited spatial resolution of PET-that may limit the assessment of small-volume malignant disease. Knowledge of the key imaging features of physiologic and nonphysiologic FDG fluorodeoxyglucose uptake, in addition to understanding the principles of adequate patient preparation and PET scanning protocols, is important for accurate interpretation of gynecologic and genitourinary oncologic FDG fluorodeoxyglucose PET/CT studies. ©RSNA, 2017.

Clinical PET Imaging in Prostate Cancer

Prostate cancer is the second most common cancer in men worldwide, with a wide spectrum of biologic behavior ranging from indolent low-risk disease to highly aggressive castration-resistant prostate cancer. Conventional imaging with computed tomography, magnetic resonance imaging, and bone scintigraphy is limited for the detection of nodal disease and distant bone metastases. In addition, advances in the available therapeutic options, both localized and systemic, drive the requirement for precise diagnostic and prognostic tools to refine the individual therapeutic approach at various times in the management of patients with prostate cancer. Positron emission tomography (PET) has a rapidly evolving role in the assessment of prostate cancer, particularly in the scenario of biochemical relapse. Fluorine 18 (18F) fluorodeoxyglucose, the most widely available PET tracer, has limitations, particularly in indolent prostate cancer. In the past decade, several PET tracers with specific molecular targets have reached the clinical domain. These tracers include 18F-sodium fluoride, which is a bone-specific biomarker of osteoblastic activity; 18F-choline and carbon 11-choline, which are directed at cell membrane metabolism; gallium 68-prostate-specific membrane antigen ligands; and, more recently, an amino acid analog, 18F-fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid; also known as FACBC), which is also directed at cell membrane turnover. The mechanisms of actions of the clinically available PET tracers are reviewed, as well as their role in the imaging of prostate cancer with reference to relevant guidelines and the technical and imaging pearls and pitfalls of these tracers. ©RSNA, 2017.

P17 Case report: Investigation of the role of positron emission tomography in the diagnosis of aortic graft infection following abdominal aortic aneurysm repair: preliminary case studies

Aim To demonstrate the role of PET in the diagnosis and monitoring of vertebral osteomyelitis, compared to MRI. Method A 47-year-old woman presented with a 2 month history of fever and rigors. The illness began whilst travelling to India where she developed diarrhoea and fever. On return to the UK she developed right sided hip pain and back pain. Salmonella paratyphi A was grown from blood cultures. Results X-ray of the lumbar spine and Tc-HMPAO white cell scan were normal. The MRI scan of the lumbar spine 1 month after presentation showed non-specific signal abnormalities in the L5-S1 disc. An F-FDG PET performed at the same time, demonstrated avid tracer uptake in the region of the L5S1 disc in keeping with acute infective disciitis/osteomyelitis. Two repeat MRI scans confirmed vertebral osteomyelitis, but showed persistent signal abnormalities even after several weeks. Two further F-FDG PET scans showed decreasing SUV of the lumbar lesion and, finally, resolution of the infection after longterm antimicrobial therapy. Conclusion The singular advantage of F-FDG PET over MRI is the ability to monitor quantitatively the response to antimicrobial treatment. The SUV is expected to decrease as antimicrobial therapy takes effect as in our case study.