Oreste Bagni

90Y PET-based dosimetry after selective internal radiotherapy treatments

Objectives The decay of 90Y has a minor branch to the O+ first excited state of 89Zr, the de-excitation of which to the fundamental state is followed by a &bgr;+–&bgr;− emission that has been used recently for biodistribution assessment after selective internal radiotherapy (SIRT) treatments. The purpose of the present study is to demonstrate the feasibility of 90Y PET imaging for dose assessment after radioembolization with 90Y microspheres. Methods Activity quantification was validated through preliminary phantom studies using a cylindrical body phantom composed of six inserts of different volumes filled with a calibrated amount of 90Y microspheres. A GE Discovery ST PET/CT scanner provided with bismuth germinate (BGO) crystals was used for image acquisition. Images were reconstructed with an ordered subset expectation–maximization method. The effect of object size and the effect of the number of iterations on dose evaluation and volume recovery were investigated. Microsphere dose distribution was then evaluated on one patient (one lesion) who underwent liver SIRT treatment. Dose calculations were made with a MATLAB-based code developed in our department. Dedicated Monte Carlo calculations were executed to evaluate dose S-values for the 90Y source. The activity distribution derived from 90Y PET acquisitions was convolved with the voxel S-values to obtain a three-dimensional absorbed dose distribution and dose–volume histograms. Results Dosimetry studies carried out on the body phantom with ordered subset expectation–maximization algorithm, three iterations, provided an accuracy of 7.62% in determining the absorbed dose in the largest insert. The dose difference increases as the insert size reduces. Preliminary results on a patient provided a high-resolution absorbed dose distribution map. An average dose of 139.3 Gy was evaluated for the tumor area, with a maximum dose as high as 237.9 Gy. The absorbed dose to the healthy liver was below the tolerance dose of 35 Gy (33.8 Gy). A clear correlation between absorbed dose and tumor response was observed at 18F-fluorodeoxyglucose PET acquired 6 months after treatment. Conclusion According to our experience, 90Y PET is a promising and reliable technique for microsphere dose assessment and might pave the way for a patient-specific PET-based dosimetry after liver SIRT treatments.

Can Sequential 18F-FDG PET/CT Replace WBC Imaging in the Diabetic Foot?

White blood cell (WBC) scintigraphy is considered the nuclear medicine imaging gold standard for diagnosing osteomyelitis in the diabetic foot. Recent papers have suggested that the use of 18F-FDG PET/CT produces similar diagnostic accuracy, but clear interpretation criteria have not yet been established. Our aim was to evaluate the role of sequential 18F-FDG PET/CT in patients with a high suspicion of osteomyelitis to define objective interpretation criteria to be compared with WBC scintigraphy. Methods: Thirteen patients whom clinicians considered positive for osteomyelitis (7 with ulcers, 6 with exposed bone) were enrolled. The patients underwent 99mTc-exametazime WBC scintigraphy with acquisition times of 30 min, 3 h, and 20 h and sequential 18F-FDG PET/CT with acquisition times of 10 min, 1 h, and 2 h. A biopsy or tissue culture was performed for final diagnosis. Several interpretation criteria (qualitative and quantitative) were tested. Results: At final biopsy, 7 patients had osteomyelitis, 2 had soft-tissue infection without osteomyelitis, and 4 had no infection. The best interpretation criterion for osteomyelitis with WBC scintigraphy was a target-to-background (T/B) ratio greater than 2.0 at 20 h and increasing with time. A T/B ratio greater than 2.0 at 20 h but stable or decreasing with time was suggestive of soft-tissue infection. A T/B ratio of no more than 2.0 at 20 h excluded an infection. Thus, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for osteomyelitis were 86%, 100%, 100%, 86%, and 92%, respectively. For 18F-FDG PET/CT, the best interpretation criterion for osteomyelitis was a maximal standardized uptake value (SUVmax) greater than 2.0 at 1 and 2 h and increasing with time. A SUVmax greater than 2.0 after 1 and 2 h but stable or decreasing with time was suggestive of a soft-tissue infection. An SUVmax less than 2.0 excluded an infection. 18F-FDG PET at 10 min was not useful. Using these criteria, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for osteomyelitis were 43%, 67%, 60%, 50%, and 54%, respectively. Combining visual assessment of PET at 1 h and CT was best for differentiating between osteomyelitis and soft-tissue infection, with a diagnostic accuracy of 62%. Conclusion: 18F-FDG PET/CT, even with sequential imaging, has a low diagnostic accuracy for osteomyelitis and cannot replace WBC scintigraphy in patients with diabetic foot.

90Y-PET for the assessment of microsphere biodistribution after selective internal radiotherapy.

ObjectivesTo demonstrate the feasibility of 90Y-PET imaging for biodistribution assessment after selective internal radiotherapy treatments with 90Y-microspheres, comparing the results with 99mTc-macroaggregated albumin (MAA) images obtained with single-photon emission computed tomography. MethodsPreliminary studies were performed with the aim of evaluating the imaging system spatial resolution and scanner sensitivity for detecting annihilation photons. Subsequently, microsphere distribution was evaluated in 10 patients who underwent liver selective internal radiotherapy treatment. 99mTc-MAA and 90Y-microsphere were simultaneously injected for immediate monitoring after treatment. For each patient, the metastases detected with 90Y-PET and 99mTc-MAA were assessed and compared with 18F-fluorodeoxyglucose-PET (18F-FDG-PET) obtained before treatment and used as an imaging benchmark procedure. The correlation between these techniques was thus investigated in terms of matching lesions. Lesions were considered true positive in the case of matching with 18F-FDG-PET. The sensitivity of both techniques was evaluated as the true-positive fraction of detected spots in the treated liver sectors. ResultsWith our experimental setup, a maximum scanner sensitivity of 0.577 and 0.077 cps/MBq was obtained for three-dimensional and two-dimensional acquisitions, respectively. A good correlation was obtained between images obtained before and after treatment, with 90Y-PET being by far the most accurate technique in detecting microsphere distribution and tumor nonhomogeneity areas. A sensitivity as high as 0.91 was obtained with 90Y-PET, whereas 99mTc-MAA imaging showed a SE of 0.75. Conclusion90Y-PET is a promising and reliable technique for microsphere biodistribution evaluation after liver selective internal radiotherapy treatment. Because of the better resolution and the possibility to perform computed tomography fusion, 90Y-PET images are more accurate than 99mTc-MAA single-photon emission computed tomography, which is now considered the gold standard for biodistribution assessment.

Incidental detection of colorectal cancer Via 18F-Choline PET/CT in a patient with recurrent prostate cancer: Usefulness of early images

A 74-year-old man with history of prostate cancer underwent F-choline PET/CT for restaging. Early acquisition of the pelvic region revealed intense uptake in prostate, with infiltration of the posterior wall of the bladder. Furthermore, focal uptake in the thickened anterior wall of the rectum was detected. Whole-body scan at 60 minutes confirmed early findings in pelvis, although the infiltration of the bladder was no more evident due to interference of radioactive urine. Biopsy demonstrated the presence of colorectal carcinoma. The dual-phase protocol resulted in significant clinical impact to clearly characterize focuses of abnormal F-choline uptake in the pelvic region.

Usefulness of dual-time point imaging after carbonated water for the fluorodeoxyglucose positron emission imaging of peritoneal carcinomatosis in colon cancer.

BACKGROUND Fluorodeoxygluose (FDG) positron emission/computed tomography (PET/CT) is emerging as a useful tool for the diagnosis of peritoneal carcinomatosis (PC). In this study, we assessed whether dual-time point imaging can improve the accuracy of FDG PET/CT for the diagnosis of PC after colon rectal cancer (CRC). METHODS Thirty-nine patients with past history of CRC were evaluated. Whole-Body PET/CT scan was acquired 1 hour after tracer injection. If one or more focal areas of increased FDG uptake (standardized uptake value, SUV max>2.5) were found in the abdomen, 1 L of carbonated water was orally administered to patients and a delayed scan of the abdominal region was acquired at 2 hours. The SUV max and the mean Delta (Δ) SUV were calculated. The scintigraphic results were compared with the results of colonoscopy and histology and with the clinical follow-up. RESULTS Thirteen out of the 39 patients did not show any significant area of FDG uptake at the whole-body scan. The remaining 26 patients showed an overall number of 27 sites of focal increased uptake, showing a mean SUV max of 6.5+3.3. Late scan of the abdomen showed vanishing spots in 11 cases. Focal and increasing FDG uptake was found in 15 subjects (for an overall number of 16 sites) with SUV max of 15.6+4 and mean Δ SUV of +26.3%±7.5%. In these cases, final diagnosis was PC in 10 patients (according to cytology or histology) and dysplastic polyp in 5 cases. No significant difference in Δ SUV was found between patients with PC and those with polypoid formations. CONCLUSIONS According to our results, dual-time point imaging after carbonated water may increase the accuracy of FDG PET/CT for the imaging of PC in patients affected by CRC.

18F-FDG PET-derived parameters as prognostic indices in hepatic malignancies after 90Y radioembolization: is there a role?

The liver is a site of prominent metastasization for many tumours, especially breast and colorectal cancers [1]. Unfortunately, despite many advances in diagnosis and therapy, the prognosis of both primary and secondary hepatic tumours remains poor. Surgery is the most effective approach, but it can often be impracticable due to the anatomic location of the lesions or the massive involvement at presentation. Several treatment modalities both systemic and loco-regional (ethanol injection, radiofrequency ablation, cryoablation, transarterial chemoembolization) have been evaluated [2, 3]. In recent years, Y radioembolization (RE) has emerged as a novel procedure used for the treatment of primary or secondary hepatic lesions. Y, embedded in resin or glass microspheres, is infused directly into the circulation through angiographic catheters placed in the hepatic arteries [4]. Y spheres, once implanted in the liver, can release a significant radiation burden to the neoplastic cells with a relatively low dose to the normal parenchyma due to the different vascularization pattern. To assess tumour response to YRE, Response Evaluation Criteria In Solid Tumours (RECIST) has been largely used [5], but it can present some limitations, since various periand endotumoural processes can occur after the procedure, including oedema, haemorrhage and ring enhancement, which can confound interpretation of response. Besides RECIST, other morphological criteria have been proposed [6]. On the other hand, 2-[F]fluorodeoxyglucose (FDG) PET/CT is a wellestablished diagnostic tool in many oncological scenarios [7]. Although it plays a limited role in the case of non-FDG-avid lesions such as some neuroendocrine tumours and welldifferentiated hepatocellular carcinoma, FDG PET appeared to be useful in detecting metabolic response to Y RE, especially in cases of colorectal and breast cancer metastases to the liver [8, 9]. Regarding the prognostic value of a PET scan, a strict relationship between FDG uptake as measured by the maximum standardized uptake value (SUVmax) and some cellular characteristics of tumours has been reported [10]. Therefore, SUVmax and its changes have been traditionally taken into account as prognostic indicators of tumour response after treatment. Furthermore, PET Response Criteria in Solid Tumors (PERCIST) criteria have been recently introduced to more accurately define the metabolic response of tumours to the therapies [11]. Haug and colleagues published research on the role of FDG PET in predicting survival after Y RE in a cohort of 58 patients with hepatic metastases from breast cancer [12]. FDGPETwas performed at baseline and 3months after the procedure. To evaluate the response of the disease to treatment, the authors applied modified PERCIST criteria. According to the unmodified PERCIST, the change of SUVmax in the two hottest lesions per organ is considered. On the contrary, Haug et al. based their definition of the response on the summed percentage change in the SUVmax in up to five of the most prominent hepatic lesions, demonstrating that response assessed with this approach correlated significantly with survival after Y RE. More recently, Camacho et al. confirmed a significant correlation between overall survival and metabolic response assessed 3 months post procedure by PERCIST criteria in patients with cholangiocarcinoma [13]. It is well known that SUVmeasurements can be affected by many issues, such as the reconstruction algorithm, the scanner O. Bagni : L. Filippi Department of Nuclear Medicine, Santa Maria Goretti Hospital, Latina, Italy

Tumor Thrombus in the Renal Vein from an Adrenal Metastasis of Lung Cancer: 18FDG PET/CT Findings

Tumor thrombus is a rare complication of solid cancer. The authors report a case of a 76-year-old woman presenting a thick walled cystic mass in the lower lobe of the left lung. 18FDG positron emission tomography (PET)/computed tomography (CT) was performed, showing tracer accumulation in the wall of the pulmonary lesion and in the mediastinal and hilar lymph nodes. Moreover, PET/CT depicted a gross mass in the left adrenal gland and a hypermetabolic focus corresponding to the anatomic location of the left renal vein. Contrast-enhanced CT, subsequently performed, confirmed PET findings in the lung, lymph nodes, and adrenal glands, also demonstrating marginal enhancement and intraluminal filling defect in the left renal vein, which was interpreted as tumor thrombus due to the 18FDG uptake at PET scan. CT-guided biopsy of the mass was positive for poorly differentiated carcinoma. 18FDG PET can be useful to diagnose tumor thrombus in oncological patients.

An unusual case of spleen metastasis from carcinoma ex pleomorphic adenoma of the parotid gland

Carcinoma ex pleomorphic adenoma is a rare tumor arising from the salivary glands that spreads through direct extension, through the lymphatic vessels, and, rarely, hematogenously. When distant metastases have been found, they have been reported mainly in the lung. We present an unusual case of carcinoma ex pleomorphic adenoma of the parotid gland with splenic metastases. The patient presented with a primary carcinoma ex pleomorphic adenoma of the parotid gland and he underwent a total parotidectomy with laterocervical lymphadenectomy ipsilateral and adjuvant radiation therapy to the right parotid area. One year later, the patient showed an ipsilateral supraclavicular lymph node recurrence, treated with surgery and radiation therapy. Two more years later, the patient developed lung and splenic lesions, detected through CT and PET. He underwent splenectomy and pathologic assessment of the specimen showed metastatic carcinoma ex pleomorphic adenoma. To our knowledge, there is no reported case of a carcinoma ex pleomorphic adenoma metastasizing to the spleen. Patients treated for carcinoma ex pleomorphic adenoma should be investigated for distant metastases with a long-term follow-up examination for local and distant metastases and new splenic lesions in these patients should be investigated.

18F-Fluorodeoxyglucose positron emission tomography-computed tomography imaging of inferior vena cava tumor thrombus extending into the right atrium in a patient with cholangiocarcinoma treated with 90Y-Microspheres

We present a case of a 42-year-old male patient affected by unresectable, chemorefractory cholangiocarcinoma, with prior placement of biliary stent. Because of the absence of extrahepatic metastases, he was submitted to liver-direct therapy with 90Y-microspheres. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) performed before the procedure showed intense tracer uptake in the hepatic lesion and along the biliary stent. The patient underwent radioembolization with 90Y-resin spheres (1.1 GBq). 18F-FDG PET-CT, acquired 6 weeks after the procedure, showed no response of the hepatic lesion and the appearance of an area of markedly increased uptake extending through the inferior vena cava into the right atrium, confirmed as extensive tumor thrombus at the enhanced multislice CT subsequently performed. 18F-FDG PET-CT proved to be a useful imaging tool not only for the evaluation of metabolic response but also for the early detection of extrahepatic progression after 90Y-radioembolization.

Yttrium-90 resin microspheres and their use in the treatment of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is a severe and rapidly progressive hepatic tumor. Surgery is often impracticable due to locally advanced presentation. On the other hand, chemotherapy has demonstrated only limited effectiveness. For these reasons, liver-directed therapies have been successfully applied for treating ICC. In particular, radioembolization with Yttrium-90 (90Y)-labeled spheres has been reported to be a promising therapeutic approach for this neoplasia. Two commercial forms of 90Y-labeled spheres are available: glass (TheraSphere®) and resin (SIR-Spheres®) microspheres. The aim of the present paper is to review the existing literature on the use of the resin microspheres for the treatment of unresectable and chemorefractory ICC, focusing on the methodology, clinical applications and side effects.