Zarni Win

Ventilation–Perfusion Scintigraphy Is More Sensitive than Multidetector CTPA in Detecting Chronic Thromboembolic Pulmonary Disease as a Treatable Cause of Pulmonary Hypertension

Pulmonary hypertension (PH) is a progressive disease with a poor prognosis. Identifying chronic thromboembolic pulmonary disease as a cause of PH has major clinical implications as these patients could be potentially offered a surgical cure. Ventilation–perfusion (V/Q) scintigraphy has a high sensitivity to detect embolic disease but its value has been challenged with the emergence of multidetector CT pulmonary angiography (CTPA). We compared the value of V/Q scintigraphy with CTPA in detecting chronic thromboembolic pulmonary disease. Methods: We retrospectively reviewed the results of V/Q scintigraphy and CTPA performed on patients who had been referred to the Pulmonary Hypertension Service at Hammersmith Hospital between 2000 and 2005. A total of 227 patients (85 males, 142 females; age range, 18–81 y; mean age, 42 y) had all tests done at Hammersmith Hospital and were included in the study. Interpretation of scans was according to the modified PIOPED (Prospective Investigation of Pulmonary Embolism Diagnosis) criteria. CTPA was considered as suggestive of chronic thromboembolic pulmonary disease if it showed visualization of the thrombus or webs, recanalization, perfusion abnormalities, stenosis, or strictures. Standard pulmonary angiography was performed via femoral approach. In 90% of the cases, CTPA and V/Q scintigraphy were performed within 10 d. Results: Seventy-eight patients (group A) had a final diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) and 149 (group B) had non-CTEPH etiology. Among group A, V/Q scintigraphy was reported as high probability in 75 patients, intermediate probability in 1 patient, and low probability in 2 patients. CTPA was positive in 40 patients and negative in 38 patients. Among group B, V/Q scintigraphy was reported as low probability in 134, intermediate probability in 7, and high probability in 8 patients. CTPA was negative in 148 patients and false-positive in 1 patient. Statistical analysis showed V/Q scintigraphy to have a sensitivity of 96%–97.4% and a specificity of 90%–95%. CTPA showed a sensitivity of 51% and a specificity of 99%. Conclusion: Our results demonstrate that V/Q scintigraphy has a higher sensitivity than CTPA in detecting CTEPH as a potential curable cause of PH.

68Ga-DOTATATE PET in neuroectodermal tumours: first experience.

Background and aimPhaeochromocytoma is initially imaged with computed tomography (CT) or magnetic resonance imaging (MRI) but functional imaging is commonly needed to assess disease activity, the presence of metastasis and response to therapy. Traditionally, this is done with 123I -MIBG with good sensitivity and specificity. However, spatial resolution remains limited even with SPECT. We aimed to assess the utility of a new somatostatin analogue PET tracer, 68Ga-DOTATATE in the management of phaeochromocytoma. MethodsWe retrospectively reviewed five patients with malignant phaeochromocytoma who underwent imaging with CT and 123I-MIBG and compared the results with those of PET imaging using 68Ga-DOTATATE. Blinded analysis of the numbers and extent of lesions were done for all imaging modality. ResultsTwo patients had negative 123I-MIBG and positive 68Ga-DOTATATE scans. One had a weakly positive 123I-MIBG and a strongly positive 68Ga-DOTATATE scan. One had a positive 123I-MIBG and positive 68Ga-DOTATATE scans. The fifth patient was negative to all imaging including CT. 68Ga-DOTATATE showed more lesions with higher uptake and better resolution compared to 123I-MIBG. ConclusionThe findings in our small group of patients demonstrate the value of somatostatin receptor PET imaging in malignant phaeochromocytoma. In lesions with no or low MIBG uptake, the next investigation of choice should be PET imaging with 68Ga-DOTATATE, in view to therapy with 90Y-labelled DOTATATE.

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.

The possible role of 68Ga-DOTATATE PET in malignant abdominal paraganglioma

Paragangliomas are rare tumours that arise within the sympathetic nervous system originating from the neural crest. Nearly 90% of these tumours originate in the medulla of the adrenal glands, and are known as phaeochromocytomas. The remaining 10% are extra-adrenal and are termed paragangliomas. In all, 10% are malignant, and these are often difficult to manage. The authors discuss the case of a 51-year-old male who presented with biochemical recurrence of a malignant abdominal paraganglioma following surgical excision 4 months previously. CT showed an extensive soft tissue mass enveloping the abdominal aorta (a, solid arrows) and the left ureter, causing hydronephrosis (a, broken arrow). This represented local recurrence of tumour at the excision site. The lesion was inoperable. The tumour did not show affinity to 123 I-MIBG (b) or 111 In-octreotide (c). An 18 FDG-PET scan demonstrated increased metabolic activity within the lesion (d, solid arrows), as well as left-sided hydronephrosis (d, broken arrow). PET imaging with 68 Ga-DOTATATE (DOTA-Tyr 3 -Thr 8 -octreotide) showed avid tracer uptake within the tumour, indicating positive somatostatin receptor status (e, solid arrows). 123 I-MIBG scan is the nuclear medicine imaging method of choice, with a cumulative sensitivity of 86% and specificity of 98% [1]. In neuroendocrine tumours, 68 Ga-DOTATOC (DOTA-D-Phe 1 -Tyr 3 -octreotide) has been shown to have higher tumour to non-tumour contrast compared with 111 In-octreotide [2, 3]. In MIBG-negative cases, imaging with 68 Ga-DOTATATE should be considered, especially if the lesion is suspected to be small. Recurrence of malignant paraganglioma is often difficult to manage, especially if the tumour is MIBG receptor negative and is not amenable to surgery. In this challenging group, positive imaging with 68 Ga-DOTATATE carries the opportunity of targeted radionuclide therapy with suitable beta emitters such as 90 YDOTATATE [4].

Anatomical and functional localization of ectopic parathyroid adenomas: 6-year institutional experience.

IntroductionLocalization of ectopic parathyroid adenoma is highly important to guide surgery, thus reducing morbidity and rate of recurrent hyperparathyroidism. The aim of this study was to establish the incidence of ectopic parathyroid adenoma and evaluate the role of multimodality imaging in diagnosis. Materials and methodsWe reviewed 656 imaging studies of patients referred for investigations of primary hyperparathyroidism. All patients suspected of having an ectopic adenoma had technetium-99m (99mTc) sestamibi (MIBI) and ultrasound of the neck. In addition, patients had cross-sectional imaging, either computed tomography (CT) or magnetic resonance imaging (MRI), in cases of suspected ectopic adenoma. Some patients also underwent angiography. Results were correlated with postoperative findings and histopathology to calculate sensitivity, specificity, positive and negative predictive values. The incidence of ectopic adenoma was also determined. ResultsIn our series, the incidence of ectopic adenoma was 1.4%, which is lower than earlier published reports in the literature. Eleven patients showed ectopic uptake suspicious of a parathyroid adenoma on 99mTc MIBI. CT confirmed the diagnosis of ectopic adenoma in seven patients and MRI showed adenoma in two patients. Surgical and histopathological findings confirmed the diagnosis of ectopic parathyroid adenoma in nine patients. Sensitivity and specificity for ultrasound were 11 and 100%, respectively. 99mTc MIBI had sensitivity, specificity, positive and negative predictive values of 100, 86, 98 and 65%, respectively.The combination of 99mTc-MIBI with CT or MRI yielded the correct diagnosis in all cases, giving a sensitivity and specificity of 100%. ConclusionThe incidence of ectopic parathyroid adenoma is much lower than previously reported. Multimodality imaging in a tertiary referral centre is the ideal approach for accurate diagnosis.

68Ga DOTATATE PET/CT uptake in spinal lesions and MRI correlation on a patient with neuroendocrine tumor: potential pitfalls.

A 62-year-old female patient with suspected insulinoma underwent 68Ga DOTA-TATE PET/CT for characterization and staging. This demonstrated a focus of uptake in the pancreas and 3 foci of uptake in the spine. An MRI of the spine performed to further characterize the lesions revealed the presence of a meningioma and degenerative changes, both of which showed 68Ga DOTA-TATE uptake. A vertebral metastasis seen on PET was occult on CT and MRI. A vertebral hemangioma had no discrete tracer uptake. Awareness of sources of error in interpreting 68Ga DOTA-TATE scans is important in order to avoid pitfalls.

Vesico-colic fistula as demonstrated by [18F]FDG-PET

With the exponential rise in worldwide experience with PET imaging we are accumulating an ever-expanding knowledge base, especially in regard to the normal variants in anatomy and physiology. Bowel activity with [F]FDG is well recognised, although not entirely understood. This is particularly evident in the large intestine and to a lesser extent in the stomach and small intestine. However, it is important to keep in mind that [F]FDG activity in the bowel may represent pathology as well as benign physiological activity. Here we present a case of vesico-colic reflux, which was demonstrated on [F]FDG-PET, and confirmed by a MAG-3 study. A 67-year-old man, with a past history of carcinoma of the recto-sigmoid treated with surgery and chemotherapy, presented with signs of clinical and radiological recurrence. A CT scan of the pelvis demonstrated a soft tissue presacral mass (a), but tissue biopsies of the lesion proved negative. An [F]FDG-PET study showed uptake in the pre-sacral mass consistent with local recurrence (b). Furthermore, intense FDG activity was noted in the descending colon (arrow), as well as suggestions of a right-sided hydronephrosis (c). A MAG-3 renogram showed a dilated, but unobstructed right renal tract (d). During the bladder filling phase, ascending MAG-3 activity was seen in a curvilinear structure lying anterolateral to the left renal tract (d). This was concordant with the [F]FDG-PET images. These findings confirm that the FDG uptake in the descending colon was due to a malignant vesico-colic fistula. Z. Win (*) . Department of Nuclear Medicine, Hammersmith Hospital, London, UK e-mail: zarni_win@hotmail.com

Occult squamous cell carcinoma of the uvula detected by F-18 FDG PET/CT in a case of carcinoma of unknown primary in the head and neck.

Incidence of unknown primary head/neck tumors with metastatic cervical lymphadenopathy at time of diagnosis is approximately 2% to 9%. Detecting site of original disease is challenging. We present a 75-year-old woman with bulky unilateral level 2 and 3 lymphadenopathy. Clinical examination and computed tomography (CT) did not reveal detectable abnormalities except neck-node metastases; biopsy indicated metastatic squamous cell carcinoma (SCC). F-18 FDG PET/CT imaging was performed to detect the primary tumor site, which revealed a small metabolically-avid lesion in uvula, biopsy demonstrated SCC, the origin of metastatic disease. F-18 FDG PET/CT imaging of unknown primary head/neck tumors can have positive impact in identifying small occult primary tumor foci.

Deep-Seated Resistance in Relapsed Paratyphoid Fever

We describe a case of relapsed paratyphoid fever in which the isolate had reduced susceptibility to ciprofloxacin due to a rare mutation within the gyrA gene. 18fluorodeoxyglucose positron emission tomography scanning identified deep-seated infection including unsuspected aortitis and highlights the utility of novel imaging techniques to improve our understanding and treatment of this disease.