Adil Al-Nahhas

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.

Phase I Trial of the Positron-Emitting Arg-Gly-Asp (RGD) Peptide Radioligand 18F-AH111585 in Breast Cancer Patients

The integrin αvβ3 receptor is upregulated on tumor cells and endothelium and plays important roles in angiogenesis and metastasis. Arg-Gly-Asp (RGD) peptide ligands have high affinity for these integrins and can be radiolabeled for PET imaging of angiogenesis or tumor development. We have assessed the safety, stability, and tumor distribution kinetics of a novel radiolabeled RGD-based integrin peptide-polymer conjugate, 18F-AH111585, and its feasibility to detect tumors in metastatic breast cancer patients using PET. Methods: The biodistribution of 18F-AH111585 was assessed in 18 tumor lesions from 7 patients with metastatic breast cancer by PET, and the PET data were compared with CT results. The metabolic stability of 18F-AH111585 was assessed by chromatography of plasma samples. Regions of interest (ROIs) defined over tumor and normal tissues of the PET images were used to determine the kinetics of radioligand binding in tissues. Results: The radiopharmaceutical and PET procedures were well tolerated in all patients. All 18 tumors detected by CT were visible on the 18F-AH111585 PET images, either as distinct increases in uptake compared with the surrounding normal tissue or, in the case of liver metastases, as regions of deficit uptake because of the high background activity in normal liver tissue. 18F-AH111585 was either homogeneously distributed in the tumors or appeared within the tumor rim, consistent with the pattern of viable peripheral tumor and central necrosis often seen in association with angiogenesis. Increased uptake compared with background (P = 0.002) was demonstrated in metastases in lung, pleura, bone, lymph node, and primary tumor. Conclusion: 18F-AH111585 designed to bind the αvβ3 integrin is safe, metabolically stable, and retained in tumor tissues and detects breast cancer lesions by PET in most anatomic sites.

Role of FDG-PET and PET/CT in the diagnosis and management of vasculitis

PURPOSE to investigate the role of FDG-PET and PET/CT in the evaluation of vasculitis. MATERIALS AND METHODS a systematic revision of the papers published in PubMed/Medline until December 2009 was done. RESULTS FDG-PET and PET/CT have been proven to be valuable in the diagnosis of large-vessel vasculitis, especially giant cells arteritis with sensitivity values ranging 77% to 92%, and specificity values ranging 89% to 100%. In particular, FDG-PET/CT has demonstrated the potential to non-invasively diagnose the onset of the vasculitis earlier than traditional anatomical imaging techniques, thus enabling prompt treatment. False positive results mainly occur in the differential diagnosis between vasculitis and atherosclerotic vessels in elderly patients. Another area where FDG-PET/CT is gaining wider acceptance is in monitoring response to therapy; it can reliably detect the earliest changes of disease improvement post-therapy, and persistent activity is an indicator of non-responders to therapy. A few data have been reported about medium/small vessel vasculitis. DISCUSSION FDG-PET and PET/CT have proven utility: (a) in the initial diagnosis of patients suspected of having vasculitis particularly in those who present with non-specific symptoms; (b) in the identification of areas of increased FDG uptake in which a biopsy should be done for obtaining a diagnosis; (c) in evaluating the extent of the disease; (d) in assessing response to treatment.

Use of [11C]Choline PET-CT as a Noninvasive Method for Detecting Pelvic Lymph Node Status from Prostate Cancer and Relationship with Choline Kinase Expression

Purpose: To evaluate the accuracy and biological basis for [11C]choline-PET-CT in the nodal staging of high risk localized prostate cancer patients. Experimental Design: Twenty-eight patients underwent dynamic [11C]choline-PET-CT of the pelvis and lower abdomen prior to extended laparoscopic pelvic lymph node dissection (eLPL). The sensitivity and specificity of [11C]choline PET, [11C]choline PET-CT, and MRI for nodal detection were calculated. Average and maximal standardized uptake values (SUVave, SUVmax) were compared with choline kinase alpha (CHKα) and Ki67 immunohistochemistry scores. Results: Four hundred and six lymph nodes (LN), in 26 patients, were assessable. Twenty-seven (6.7%) involved pelvic nodes at eLPL were detected in 9 patients. Seventeen of the 27 involved nodes were subcentimeter. The sensitivity and specificity on a per nodal basis were 18.5% and 98.7%, 40.7% and 98.4%, and 51.9% and 98.4% for MRI, [11C]choline PET, and [11C]choline PET-CT, respectively. Sensitivity was higher for [11C]choline PET-CT compared with MRI (P = 0.007). A higher nodal detection rate, including subcentimeter nodes, was seen with [11C]choline PET-CT than MRI. Malignant lesions showed CHKα expression in both cytoplasm and nucleus. SUVave and SUVmax strongly correlated with CHKα staining intensity (r = 0.68, P < 0.0001 and r = 0.63, P = 0.0004, respectively). In contrast, Ki67 expression was generally low in all tumors. Conclusion: This study establishes the relationship between [11C]choline PET-CT uptake with choline kinase expression in prostate cancer and allows it to be used as a noninvasive means of staging pelvic LNs, being highly specific and more sensitive than MRI, including the detection of subcentimeter disease. Clin Cancer Res; 17(24); 7673–83. ©2011 AACR.

[18F]-3′Deoxy-3′-Fluorothymidine Positron Emission Tomography and Breast Cancer Response to Docetaxel

Purpose: To establish biomarkers indicating clinical response to taxanes, we determined whether early changes in [18F]-3′deoxy-3′-fluorothymidine positron emission tomography (FLT-PET) can predict benefit from docetaxel therapy in breast cancer. Experimental Design: This was a prospective unblinded study in 20 patients with American Joint Committee on Cancer (AJCC) stage II–IV breast cancer unresponsive to first-line chemotherapy or progressing on previous therapy. Individuals underwent a baseline dynamic FLT-PET scan followed by a scan 2 weeks after initiating the first or second cycle of docetaxel. PET variables were compared with anatomic response midtherapy (after 3 cycles). Results: Average and maximum tumor standardized uptake values at 60 minutes (SUV60,av and SUV60,max) normalized to body surface area ranged between 1.7 and 17.0 and 5.6 and 26.9 × 10−5 m2/mL, respectively. Docetaxel treatment resulted in a significant decrease in FLT uptake (P = 0.0003 for SUV60,av and P = 0.0002 for SUV60,max). Reduction in tumor SUV60,av was associated with target lesion size changes midtherapy (Pearson R for SUV60,av = 0.64; P = 0.004) and predicted midtherapy target lesion response (0.85 sensitivity and 0.80 specificity). Decreases in SUV60,av in responders were due, at least in part, to reduced net intracellular trapping of FLT (rate constant, Ki). Docetaxel significantly reduced Ki by 51.1% (±28.4%, P = 0.0009). Conclusion: Changes in tumor proliferation assessed by FLT-PET early after initiating docetaxel chemotherapy can predict lesion response midtherapy with good sensitivity warranting prospective trials to assess the ability to stop therapy in the event of non–FLT-PET response. Clin Cancer Res; 17(24); 7664–72. ©2011 AACR.

68ga-dota-noc: a new Pet tracer for evaluating patients with bronchial carcinoid

BackgroundConventional imaging techniques [computed tomography (CT), ultrasound, magnetic resonance] and somatostatin receptor scintigraphy are often insufficient to make a conclusive diagnosis of bronchial carcinoid (BC). PET is commonly used for the assessment of lung cancer but 18F-fluorodeoxyglucose, the most frequently used PET tracer, presents a low sensitivity for the detection of neuroendocrine tumours (NETs). New PET radiopharmaceuticals such as 68Ga-DOTA peptides, which directly bind to somatostatin receptors and are usually expressed on NET cell surfaces, have been reported to be superior to both morphological and somatostatin receptor scintigraphy imaging for gastroenteropancreatic NETs. However, their role in BC has never been evaluated. Our aim is to evaluate the role of 68Ga-DOTA-NOC (68Ga-labelled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide) PET for the assessment of BC patients. MethodsTen patients with pathologically proven well-differentiated BC and one patient with highly suggestive CT images for BC were studied by 68Ga-DOTA-NOC PET/CT. PET findings were compared with clinical follow-up, pathology and contrast-enhanced CT findings. Results68Ga-DOTA-NOC PET/CT detected at least one lesion in nine of 11 patients and was negative in two. PET/CT and contrast-enhanced CT were discordant in eight of 11 patients, whereas in only three patients both provided similar results. PET/CT detected a higher number of lesions in five patients and excluded malignancy at sites considered positive on CT in three of 11; follow-up confirmed PET/CT findings in all patients. In PET/CT-positive patients, the mean maximal standardized uptake value was 25.9 [4.4–60.5]. On a clinical basis, PET/CT provided additional information in nine of 11 patients leading to the changes in the clinical management of three of nine patients. ConclusionPET/CT with 68Ga-DOTA-NOC was useful in BC patients because it led to a better evaluation of the extent of the disease.

Dual PET/CT with 18F-DOPA and 18F-FDG in metastatic medullary thyroid carcinoma and rapidly increasing calcitonin levels: Comparison with conventional imaging

BACKGROUND To evaluate the role of a multi-imaging PET with (18)F-DOPA and (18)F-FDG in comparison with conventional imaging (CI) in recurrent medullary thyroid carcinoma (MTC). METHODS 18 MTC patients who had thyroidectomy were included; they presented with elevated and rapidly increasing calcitonin levels during follow up. CI had revealed metastatic deposits in 9 patients. Patients were referred to us for a PET/CT with (18)F-DOPA and (18)F-FDG. Histologic/cytologic confirmation of recurrent MTC was obtained in at least one PET-positive lesion in all patients. RESULTS Foci of abnormal uptake were observed in 15 patients at (18)F-DOPA and in 11 at (18)F-FDG; 8 patients showed the same number of positive lesions with both tracers, 2 showed more lesions on (18)F-FDG, 1 was positive at (18)F-FDG alone and 5 at (18)F-DOPA alone. In 3 patients with a DOPA-positive loco-regional relapse a re-operation with curative intent was offered. SUV(max) values were higher for (18)F-FDG compared to (18)F-DOPA (mean 12.7+/-4.1 vs. 5.5+/-2.1, p<0.05). Calcitonin was higher in PET-positive patients compared to PET negative ones, while no significant differences were observed between (18)F-DOPA and (18)F-FDG positive patients. CONCLUSIONS In MTC patients with rapidly increasing calcitonin levels during follow up, (18)F-DOPA has a good sensitivity and a complementary role with (18)F-FDG PET/CT in detecting metastatic deposits. In our experience, the sensitivity of a multi-imaging (18)F-DOPA &(18)F-FDG PET/CT approach is greater than that obtained with CI. The higher SUV(max) values found with (18)F-FDG in some patients may reflect more aggressive tumors.

Role of 18F-choline PET/CT in biochemically relapsed prostate cancer after radical prostatectomy: correlation with trigger PSA, PSA velocity, PSA doubling time, and metastatic distribution.

Purpose The aim of this study was to evaluate the efficacy of 18F-choline PET/CT (18FCH-PET/CT) in restaging patients previously treated by radical prostatectomy for a prostate cancer, presenting with biochemical relapse during follow-up (FU). Patients and Methods Three hundred thirty-one patients referred to us from January 2009 to April 2011 to perform 18FCH PET/CT were evaluated: 233 of them (mean age 69.7 years) met the inclusion criteria of the study: (1) biochemical relapse after radical prostatectomy (trigger PSA >0.2 ng/mL) (n = 224) and (2) high risk for relapse (elevated Gleason score ≥8) in spite PSA <0.1 ng/mL during FU (n = 9). Trigger PSA was available for all patients (mean 8 ng/mL) and in 44 of them also PSA kinetic (PSA velocity—PSAvel; PSA doubling time—PSAdt). Correlation between 18FCH PET/CT detection rate and trigger PSA, PSAvel, PSAdt, and tumoral spread distribution were evaluated by univariate and multivariate analysis. Subsequent minimum FU was 1 year (mean 26 months, range 12–40). Results Overall detection rate of 18FCH PET/CT was 54%, which significantly increased when the trigger PSA increases (P < 0.001). PET-positive patients presented a “fast” PSA kinetic (mean PSAdt = 6 months and mean PSAvel = 9.3 ng/mL/yr), while PET-negative patients presented a “slow” PSA kinetic (mean PSAdt = 15.4 months and mean PSAvel = 0.9 ng/mL/yr). Disease relapse was local in 17% of cases, distant in 66%, and combined in 17%. Conclusions Overall 18FCH PET/CT detection rate was 54% (ie, similar to that reported in literature with 11C-choline), which increases with the increase in trigger PSA: this condition was particularly true in patients with accelerated PSA kinetic. In about 20% of patients, 18FCH PET/CT demonstrated local relapses early enough to offer locoregional radiation therapy.

Modern Nuclear Imaging for Paragangliomas: Beyond SPECT

Paragangliomas are rare neuroendocrine tumors that may arise anywhere along the paraganglial system, with a high frequency of hereditary forms or multifocal disease. Most often, paragangliomas are benign and progress slowly, but metastases may occur in about 10% of patients. In this respect, nuclear imaging in combination with anatomic imaging may be required to fully delineate the extent of the disease. PET has been increasingly used in imaging paraganglioma, paralleled by great efforts toward the development of new tracers. Recent data indicate that the choice of PET tracers should be tailored to tumor localization and to the patients genetic status. This article provides insight into the many PET radiotracers that are currently available and others that are still only under research and guides clinicians toward appropriate use in relation to genetic carrier status. In addition, this article provides nuclear medicine physicians with the background knowledge required for understanding relationships between imaging phenotypes and molecular genetics.

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.