International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres.

PURPOSE: A multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-resin microspheres. METHODS: A steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%-79%, no agreement ≤ 49%). RESULTS: Forty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99mTc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100-120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement). CONCLUSION: Practitioners are encouraged to work towards adoption of these recommendations.

FDG-PET assessment and metabolic patterns in Lafora disease.

PURPOSE: To describe cerebral glucose metabolism pattern as assessed by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in Lafora disease (LD), a rare, lethal form of progressive myoclonus epilepsy caused by biallelic mutations in EPM2A or NHLRC1. METHODS: We retrospectively included patients with genetically confirmed LD who underwent FDG-PET scan referred to three Italian epilepsy centers. FDG-PET images were evaluated both visually and using SPM12 software. Subgroup analysis was performed on the basis of genetic and clinical features employing SPM. Moreover, we performed a systematic literature review of LD cases that underwent FDG-PET assessment. RESULTS: Eight Italian patients (3M/5F, 3 EPM2A/5 NHLRC1) underwent FDG-PET examination after a mean of 6 years from disease onset (range 1-12 years). All patients showed bilateral hypometabolic areas, more diffuse and pronounced in advanced disease stages. Most frequently, the hypometabolic regions were the temporal (8/8), parietal (7/8), and frontal lobes (7/8), as well as the thalamus (6/8). In three cases, the FDG-PET repeated after a mean of 17 months (range 7-36 months) showed a metabolic worsening compared with the baseline examination. The SPM subgroup analysis found no significant differences based on genetics, whereas it showed a more significant temporoparietal hypometabolism in patients with visual symptoms compared with those without. In nine additional cases identified from eight publications, FDG-PET showed heterogeneous findings, ranging from diffusely decreased cerebral glucose metabolism to unremarkable examinations in two cases. CONCLUSIONS: FDG-PET seems highly sensitive to evaluate LD at any stage and may correlate with disease progression. Areas of decreased glucose metabolism in LD are extensive, often involving multiple cortical and subcortical regions, with thalamus, temporal, frontal, and parietal lobes being the most severely affected. Prospective longitudinal collaborative studies are needed to validate our findings.

Yttrium-90 microsphere radioembolization in unresectable intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma is increasing in frequency worldwide, but radical surgical treatment is practicable in 30-40% of cases. The median survival without therapy is about 8 months, increased to 12 months in combination with systemic chemotherapy. Therefore, locoregional therapies, such as, radiofrequency ablation or transarterial chemoembolization have been employed. Radioembolization with yttrium-90 microspheres (90Y-TARE) is a novel intrarterial treatment which could be included in the armamentarium of treatment options, having shown higher median survival (up to 22 months) and low complication rates. Evidence-based algorithms for staging and allocation to treatment should be defined in the future, after robust results obtained through randomized controlled trials, thus establishing the exact role and timing of 90Y-TARE in the treatment protocol of unresectable intrahepatic cholangiocarcinoma.

Yttrium-90 radioembolization for unresectable/recurrent intrahepatic cholangiocarcinoma: a survival, efficacy and safety study.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a rapidly progressing malignancy; only a minority of the tumours can be resected and the palliative regimens have shown limited success. The aim of this study was to assess overall survival (OS), tumour response and the safety of radioembolization with yttrium-90 ((90)Y-TARE) in patients with unresectable/recurrent ICC. METHODS: Survival was calculated from the date of the (90)Y-TARE procedure. Target and overall Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) and European Association for the Study of the Liver (EASL)-measuring delayed-phase contrast enhancement-treatment responses were assessed at 3 months. RESULTS: The overall median survival was 17.9 months (95% CI: 14.3-21.4 months). Significantly longer survival was obtained in naive patients as compared with patients in whom TARE was preceded by other treatments, including surgery (52 vs 16 months, P=0.009). Significantly prolonged OS was recorded for patients with a response based on mRECIST and the EASL criteria while RECIST responses were not found to be associated with survival. Treatment was well-tolerated, and no mortality was reported within 30 days. CONCLUSIONS: In unresectable ICC, (90)Y-TARE is safe and offers a survival benefit in naive patients, as well as in responders.

Use of the bolus tracking technique for the tomographic evaluation of the uretero-vesicular junction in dogs and assessment of dose records.

BACKGROUND: The aim of the work is the application of a bolus tracking technique for tomographic evaluation of the uretero-vesicular junction in dogs. Ten adult dogs (8-14 years) with variable body weight (2,8-32 kg) were enrolled in the prospective study. The patients were placed in sternal recumbency with a 10° elevated pelvis and the visualization of the uretero-vesicular junction was obtained with the bolus tracking technique after intravenous administration of non-ionic contrast medium. In the post-contrast late phase a region of interest was placed within the lumen of the distal ureters and the density values were monitored before starting the helical scan. RESULTS: The uretero-vesicular junction was clearly visible in 100% of patients with the visualization of the endoluminal ureteral contrast enhancement and bladder washout. At the end of the tomographic study an evaluation of the dose records was performed and compared to human exposures reported in literature for the pelvic region. The effective dose estimated for each patient (37,5-138 mSv) proved to be elevated, when compared to those reported in human patients. CONCLUSION: The bolus tracking technique could be applied for the visualization of the uretero-vesicular junction in non-pathological patients, placing the region of interest in the distal ureters. The high effective doses recorded in our study support the need of specific thresholds for veterinary patients, pointing out the attention for paediatric patient's exposure also in veterinary imaging.

Yttrium-90 radioembolization vs sorafenib for intermediate-locally advanced hepatocellular carcinoma: a cohort study with propensity score analysis.

BACKGROUND & AIMS: Sorafenib and transarterial (90) Y-radioembolization (TARE) are possible treatments for Barcelona Clinic Liver Cancer (BCLC) intermediate-advanced stage hepatocellular carcinoma (HCC). No study directly comparing sorafenib and TARE is currently available. This single-centre retrospective study compares the outcomes achieved with sorafenib and TARE in HCC patients potentially amenable to either therapy. METHODS: Seventy-four sorafenib (71 ± 10 years, male 87%, BCLC B/C 53%/47%) and 63 TARE HCC patients (66 ± 9 years, male 79%, BCLC B/C 41%/59%) were included based on the following criteria: Child-Pugh class A/B, performance status ≤1, HCC unfit for other effective therapies, no metastases and no previous systemic chemotherapy. RESULTS: Median overall survivals of the two groups were comparable, being 14.4 months (95% CI: 4.3-24.5) in sorafenib and 13.2 months (95% CI: 6.1-20.2) in TARE patients, with 1-, 2- and 3-year survival rates of 52.1%, 29.3% and 14.7% vs 51.8%, 27.8% and 21.6% respectively. Two TARE patients underwent liver transplantation after successful down-staging. To minimize the impact of confounding factors on survival analysis, propensity model matched 32 patients of each group for median age, tumour gross pathology and the independent prognostic factors (portal vein thrombosis, performance status, Model for End Liver Disease). Even after matching, the median survival did not differ between sorafenib (13.1 months; 95% CI: 1.2-25.9) and TARE patients (11.2 months; 95% CI: 6.7-15.7), with comparable 1-, 2- and 3-year survival rates. CONCLUSIONS: In cirrhotic patients with intermediate-advanced or not-otherwise-treatable HCC, sorafenib and TARE provide similar survivals. Down-staging allowing liver transplantation only occurred after TARE.

Efficacy of radioembolization according to tumor morphology and portal vein thrombosis in intermediate-advanced hepatocellular carcinoma.

PURPOSE: We analyzed overall survival (OS) following radioembolization according to macroscopic growth pattern (nodular vs infiltrative) and vascular invasion in intermediate-advanced hepatocellular carcinoma (HCC). METHODS: Between September 2005 and November 2013, 104 patients (50.0% portal vein thrombosis [PVT], 29.8% infiltrative morphology) were treated. RESULTS: Median OS differed significantly between patients with segmental and lobar or main PVT (p = 0.031), but was 17 months in both those with patent vessels and segmental PVT. Median OS did not differ for infiltrative and nodular HCC. Median OS was prolonged in patients with a treatment response at 3 months (p = 0.023). Prior TACE was also a significant predictor of improved OS. CONCLUSION: A further indication for radioembolization might be infiltrative HCC, since OS was similar to nodular types.

Selective transarterial radioembolisation of unresectable liver-dominant colorectal cancer refractory to chemotherapy.

PURPOSE: The target lesion response (according to the Choi criteria), safety and survival following selective or superselective transarterial radioembolisation using yttrium-90-resin microspheres ((90)Y-RE) were evaluated in patients with unresectable, chemotherapy-refractory colorectal cancer liver metastases (mCRC). MATERIALS AND METHODS: A prospective case series evaluated 52 consecutive patients with mCRC who were treated at a single centre following a median of 2 lines of chemotherapy. RESULTS: Nearly half (46.2 %) of the 52 patients had a prior resection of the liver. At baseline, mCRC was limited to the liver (in 56.9 %), liver plus extra-hepatic metastases (23.5 %) or liver plus lung micro-nodules (19.6 %). Disease control rates of target lesions (partial response plus stable disease) at 3 and 6 months post-(90)Y-RE were 59 and 29 %, respectively. Target lesions were sufficiently downsized in two patients for hepatic resection and in one patient for radiofrequency ablation. Median Kaplan-Meier survival was 11.0 months (95 % confidence interval: 8.0-14.0 months) overall and 12.0 months in liver-only disease (±lung micro-nodules). Determinants of prolonged survival were response at 3 months (P = 0.046), ≤5 liver nodules (P = 0.004), single-liver-lobe involvement (P = 0.037), tumour-to-whole liver ratio <25 % (P = 0.021) and absence of extrahepatic metastases (P = 0.045). Adverse events possibly related to the nontarget distribution of (90)Y-RE were grade 1 (90)Y-RE-induced liver disease (n = 1), grade 2 and 3 gastric ulcers (n = 2). CONCLUSION: These results confirm the effectiveness and safety of selective (90)Y-RE in patients with chemotherapy-refractory mCRC, showing (90)Y-RE's potential as a bridging therapy to subsequent resection even in this end-stage population.

Comparison of 18F-FACBC and 11C-choline PET/CT in patients with radically treated prostate cancer and biochemical relapse: preliminary results.

PURPOSE: We assessed the rate of detection rate of recurrent prostate cancer by PET/CT using anti-3-(18)F-FACBC, a new synthetic amino acid, in comparison to that using (11)C-choline as part of an ongoing prospective single-centre study. METHODS: Included in the study were 15 patients with biochemical relapse after initial radical treatment of prostate cancer. All the patients underwent anti-3-(18)F-FACBC PET/CT and (11)C-choline PET/CT within a 7-day period. The detection rates using the two compounds were determined and the target-to-background ratios (TBR) of each lesion are reported. RESULTS: No adverse reactions to anti-3-(18)F-FACBC PET/CT were noted. On a patient basis, (11)C-choline PET/CT was positive in 3 patients and negative in 12 (detection rate 20%), and anti-3-(18)F-FACBC PET/CT was positive in 6 patients and negative in 9 (detection rate 40%). On a lesion basis, (11)C-choline detected 6 lesions (4 bone, 1 lymph node, 1 local relapse), and anti-3-(18)F-FACBC detected 11 lesions (5 bone, 5 lymph node, 1 local relapse). All (11)C-choline-positive lesions were also identified by anti-3-(18)F-FACBC PET/CT. The TBR of anti-3-(18)F-FACBC was greater than that of (11)C-choline in 8/11 lesions, as were image quality and contrast. CONCLUSION: Our preliminary results indicate that anti-3-(18)F-FACBC may be superior to (11)C-choline for the identification of disease recurrence in the setting of biochemical failure. Further studies are required to assess efficacy of anti-3-(18)F-FACBC in a larger series of prostate cancer patients.

Improved Survival after Transarterial Radioembolisation for Hepatocellular Carcinoma Gives the Procedure Added Value.

BACKGROUND: Transarterial Radioembolisation (TARE) requires multidisciplinary experience and skill to be effective. The aim of this study was to identify determinants of survival in patients with hepatocellular carcinoma (HCC), focusing on learning curves, technical advancements, patient selection and subsequent therapies. METHODS: From 2005 to 2020, 253 patients were treated. TARE results achieved in an initial period (2005-2011) were compared to those obtained in a more recent period (2012-2020). To isolate the effect of the treatment period, differences between the two periods were balanced using "entropy balance". RESULTS: Of the 253 patients, 68 were treated before 2012 and 185 after 2012. In the second period, patients had an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 1 (p = 0.025) less frequently, less liver involvement (p = 0.006) and a lesser degree of vascular invasion (p = 0.019). The median overall survival (OS) of patients treated before 2012 was 11.2 months and that of patients treated beginning in 2012 was 25.7 months. After reweighting to isolate the effect of the treatment period, the median OS of patients before 2012 increased to 16 months. CONCLUSIONS: Better patient selection, refinement of technique and adoption of personalised dosimetry improved survival after TARE. Conversely, sorafenib after TARE did not impact life expectancy.

Usefulness and limitations of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in the aetiological diagnosis of amyloidotic cardiomyopathy.

PURPOSE: We previously reported in a small series of patients that (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) scintigraphy tested positive in transthyretin-related (TTR) (both mutant and wild-type) but not in primary (AL) amyloidotic cardiomyopathy (AC). We extended our study to a larger cohort of patients with AC. METHODS: We evaluated (1) 45 patients with TTR-related AC (28 mutant and 17 wild-type), (2) 34 with AL-related AC and (3) 15 non-affected controls. Myocardial uptake of (99m)Tc-DPD (740 MBq i.v.) was semiquantitatively and visually assessed at 5 min and at 3 h. RESULTS: Heart retention (HR) and heart to whole-body retention ratio (H/WB) of late (99m)Tc-DPD uptake were higher among TTR-related AC (HR 7.8%; H/WB 10.4) compared with both unaffected controls (HR 3.5%; H/WB 5.7; p < 0.0001) and AL-related AC (HR 4.0%; H/WB 6.1; p < 0.0001). For the diagnosis of TTR-related AC, positive and negative predictive accuracy of visual scoring of cardiac retention were: 80 and 100% (visual score ≥1); 88 and 100% (visual score ≥2); and 100 and 68% (visual score = 3). At adjusted linear regression analysis, TTR aetiology turned out to be the only positive predictor of increasing (99m)Tc-DPD uptake in terms of both HR [ß 2.5, 95% confidence interval (CI) 1.5-3.5; p < 0.0001] and H/WB (ß 3.5, 95% CI 2.1-4.9; p < 0.0001). CONCLUSION: While (99m)Tc-DPD scintigraphy was confirmed to be useful for differentiating TTR from AL-related AC, diagnostic accuracy was lower than previously reported due to a mild degree of tracer uptake in about one third of AL patients. (99m)Tc-DPD scintigraphy can provide an accurate differential diagnosis in cases of absent or intense uptake evaluated by visual score.

The role of hepatobiliary scintigraphy combined with spect/ct in predicting severity of liver failure before major hepatectomy: a single-center pilot study.

Hepatobiliary scintigraphy (HBS) has been demonstrated to predict post-hepatectomy liver failure (PHLF). However, existing cutoff values for future liver remnant function (FLR-F) were previously set according to the "50-50 criteria" PHLF definition. Methods of calculation and fields of application in liver surgery have changed in the meantime. The aim of this study was to demonstrate the role of HBS combined with single photon emission computed tomography (SPECT/CT) in predicting severity of PHLF, according to the International Study Group of Liver Surgery (ISGLS). All patients submitted to major hepatectomy with preoperative HBS-SPECT/CT between November 2016 and December 2019, were analyzed. Patients were resected according to hepatic volumetry. Receiver operating characteristic (ROC) curve analysis was performed to identify cutoffs of FLR function for predicting PHLF according to ISGLS definition and grading. Of the 38 patients enrolled, 26 were submitted to one-stage hepatectomy (living liver donors = 4) and 12 to two-stage procedures (portal vein embolization = 4, ALPPS = 8). Overall, 18 patients developed PHLF according to ISGLS criteria: 12 of grade A (no change in the patient's clinical management) and 6 of grade B (change in clinical management). ROC analysis established increasingly higher cutoffs of FLR-F for predicting PHLF according to the "50-50 criteria", ISGLS grade B and ISGLS grade A/B, respectively. HBS with SPECT/CT may help to assess severity of PHLF following major hepatectomy. Prospective multicenter trials are needed to confirm the effective role of HBS-SPECT/CT in liver surgery.

How Do the More Recent Reconstruction Algorithms Affect the Interpretation Criteria of PET/CT Images?

PURPOSE: Recently, a new Bayesian Penalized Likelihood (BPL) Reconstruction Algorithm was introduced by GE Healthcare, Q.Clear; it promises to provide better PET image resolution compared to the widely used Ordered Subset Expectation Maximization (OSEM). The aim of this study is to compare the performance of these two algorithms on several types of findings, in terms of image quality, lesion detectability, sensitivity, and specificity. METHODS: Between September 6th 2017 and July 31st 2018, 663 whole body 18F-FDG PET/CT scans were performed at the Nuclear Medicine Department of S. Martino Hospital (Belluno, Italy). Based on the availability of clinical/radiological follow-up data, 240 scans were retrospectively reviewed. For each scan, a hypermetabolic finding was selected, reporting both for OSEM and Q.Clear: SUVmax and SUVmean values of the finding, the liver and the background close to the finding; size of the finding; percentage variations of SUVmax and SUVmean. Each finding was subsequently correlated with clinical and radiological follow-up, to define its benign/malignant nature. RESULTS: Overall, Q.Clear improved the SUV values in each scan, especially in small findings (< 10 mm), high SUVmax values (≥ 10), and medium/low backgrounds. Furthermore, Q.Clear amplifies the signal of hypermetabolic findings without modifying the background signal, which leads to an increase in signal-to-noise ratio, improving overall image quality. Finally, Q.Clear did not affect PET sensitivity or specificity, in terms of number of reported findings and characterization of their nature. CONCLUSIONS: Q.Clear is an iterative algorithm that improves significantly the quality of PET images compared to OSEM, increasing the SUVmax of findings (in particular for small findings) and the signal-to-noise ratio. However, due to the intrinsic characteristics of this algorithm, it will be necessary to adapt and/or modify the current interpretative criteria based of quantitative evaluation, to avoid an overestimation of the disease burden.

18F-FDG PET/CT in myeloma with presumed solitary plasmocytoma of bone.

AIM: To evaluate the value of 18F-fluorodeoxy-glucose (FDG) positron emission tomography with computed tomography (PET/CT) in myeloma in patients presenting with a solitary plasmacytoma of bone (SPB). PATIENTS AND METHODS: Fourteen consecutive patients studied since 2006, all having a diagnosis of SPB before PET/CT imaging took part in this study. In 3 patients PET/CT was performed for staging while in the remaining 11 it was used to monitor therapy. PET/CT was performed using a dedicated tomograph 60-90 minutes after intravenous injection of 53 MBq/kg of 18F-FDG and the results were compared to other diagnostic procedures [radiographs and magnetic resonance imaging (MRI)], biopsy, and other available follow-up data. RESULTS: In 8/14 patients, PET/CT scans showed previously unsuspected sites of increased FDG accumulation. In 6/8 patients, FDG uptake was considered pathologic, depicting myeloma involvement in bone, while in the remaining cases, findings were considered incidental and not related to myeloma. PET findings attributed to myeloma were confirmed (i.e. true positives) in 6/6 cases (100%) and in all patients with findings reported as non-pathologic, myeloma was excluded (100% true negatives). CONCLUSION: Our preliminary data in a small number of cases suggests that there are a group of patients with SPB (local disease) in whom FDG PET/CT may detect other unsuspected sites of bone involvement, upstaging the extent of the disease. In these cases, SPB may be a local manifestation of multiple myeloma where other sites of involvement have eluded detection by other less sensitive imaging modalities (i.e. skeletal surveys) or anatomically restricted imaging (i.e., less than total body MR or CT). Finding other sites of involvement have significant implications for appropriate treatment of myeloma.

Contrast enhanced magnetic resonance imaging of the foot in horses using intravenous versus regional intraarterial injection of gadolinium.

The use of contrast enhanced magnetic resonance imaging (MRI) for the detection of orthopedic pathologies in equine patients is poorly described. In few studies, enhanced MRI allowed to differentiate active lesions from chronic ones and to classify ambiguous lesions. The aim of this clinical prospective pilot study is to describe and compare the MRI lesions observed in horses with lameness localized to the foot using a single intravenous bolus dose of gadolinium contrast versus regional intraarterial bolus of contrast agent. Ten horses that underwent contrast enhanced MRI were included in the study. Gadolinium was injected intravenously in 3 patients and in 7 horses contrast agent was administered by intraarterial regional delivery. Regions of interest (ROI) were collected from both pre- and post-contrast images and ratios between pre- and post-contrast ROIs were calculated. No adverse reactions were noted after contrast agent injection. Injured structures that revealed greater increase in signal in post-contrast images were the deep digital flexor tendon (DDFT), the navicular spongiosa and the peritendinous tissues. Regional intraarterial administration of gadolinium provided higher ratio of contrast enhancement. Enhanced MRI using both intravenous or intraarterial injection of gadolinium, increased the diagnostic capability of MRI in horses with foot lesions. Nevertheless, regional intraarterial administration of gadolinium was considered the best choice due to the higher signal and lower volumes of contrast agent required.

Assessment of a chemically induced model of lung squamous cell carcinoma in mice by 18F-FDG small-animal PET.

BACKGROUND: Small-animal imaging has become a relevant research field in pre-clinical oncology. In particular, metabolic information provided by small-animal positron emission tomography (PET) is very useful to closely monitor tumour growth and assess therapy response in murine models of human disease. There are various murine models for human lung adenocarcinoma, but those for squamous cell lung carcinoma, the most common form of human cancer, are lacking. AIM: To assess the feasibility of 18F-FDG small-animal PET to monitor tumour growth in a chemically induced model of squamous cell carcinoma of the lung. MATERIALS AND METHODS: Nineteen NIH Swiss mice were skin painted by N-nitroso-tris-chloroethylurea (NTCU) twice a week, with a 3 day interval, for 8 months and 10 NIH Swiss mice skin painted with NTCU solvent (acetone) were used as controls. 18F-FDG PET was performed under sevofluorane anaesthesia and oxygen supplementation at 2, 4, 6 and 8 months from initial treatment. Images were assessed by visual analysis and semi-quantitatively. When a diffuse distribution of tumour was noted, the mean of the counts/pixel measured at three lung levels, corrected for the effective dose injected and for decay, was used for comparison between mutagen-painted and control mice. Pathological evaluation was carried out from the time of the first positive PET results in a subgroup of the whole population to assess correlation with PET findings. Small animal CT was performed at 8 months in another subgroup. RESULTS: In both terms of visual analysis and measurement of total lung activity, 18F-FDG PET at 2 and 4 months from initial treatment were comparable in mutagen-painted and controls. At 6 months, PET images showed a faint and diffuse uptake over both lung fields in mutagen-painted mice with multiple focal areas of increased tracer uptake that merged into confluent masses at 8 months and seriously subverting lung architecture on computed tomography. Total lung activity was significantly higher in mutagen-painted versus control mice at 6 (P=0.00000668) and 8 months (P=0.00000043) from initial treatment and paralleled the progressive lung involvement and histological severity. CONCLUSIONS: 18F-FDG PET may be useful in the assessment of this chemically induced murine model of lung squamous cells carcinoma. The total lung activity may be used as a measure of tumour metabolic activity of the tumour-bearing animals and may be useful in new drug testing studies.

Retro-orbital injection is an effective route for radiopharmaceutical administration in mice during small-animal PET studies.

BACKGROUND AND AIM: Small-animal PET is acquiring importance for pre-clinical studies. In rodents, radiotracers are usually administrated via the tail vein. This procedure can be very difficult and time-consuming as soft tissue extravasations are very frequent and tail scars can prevent repeated injections after initial failure. The aim of our study was to compare the retro-orbital (RO) versus tail vein intravenous (i.v.) administration of (18)F-FDG and (11)C-choline in mice for small-animal PET studies. METHODS: We evaluated four healthy female ICR CD1 mice according to the following protocol. Day 1: each animal underwent an i.v. injection of 28 MBq of (11)C-choline. PET scan was performed after 10 min and 40 min. Day 2: each animal received an RO injection of 28 MBq of (11)C-choline. A PET scan was performed after 10 min and 40 min. Day 3: each animal received an i.v. injection of 28 MBq of (18)F-FDG. A PET scan was performed after 60 min and 120 min. Day 4: each animal received an RO injection of 28 MBq of (18)F-FDG. A PET scan was performed after 60 min and 120 min. Administration and image acquisition were performed under gas anaesthesia. For FDG studies the animals fasted for 2 h and were kept asleep for 20-30 min after injection, to avoid muscular uptake. Images were reconstructed with 2-D OSEM. For each scan ROIs were drawn on liver, kidneys, lung, brain, heart brown fat and muscles, and the SUV was calculated. We finally compared choline i.v. standard acquisition to choline RO standard acquisition; choline i.v. delayed acquisition to choline RO delayed acquisition; FDG i.v. standard acquisition to FDG RO standard acquisition; FDG i.v. delayed acquisition to FDG RO delayed acquisition. RESULTS: The RO injections for both (18)F-FDG and (11)C-choline were comparable to the intravenous injection of F-FDG for the standard and delayed acquisitions. CONCLUSION: The RO administration in mice represents a technical advantage over intravenous administration in being an easier and faster procedure. However, its use requires high specific activity while its value in peptides and other receptor-specific radiopharmaceuticals needs further assessment.

11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma.

BACKGROUND: Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. AIM: As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. METHODS: Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. RESULTS: Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). CONCLUSION: According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.