Current role of 111In-DTPA-octreotide scintigraphy in diagnosis of thymic masses.

AIMS AND BACKGROUND: Thymic tumors (thymomas and thymic carcinomas) represent 50% of all mediastinal tumors. Thymomas usually express high levels of somatostatin receptors, which enable in vivo imaging with 111In-DTPA-octreotide (OctreoScan®). The aim of this study was to further investigate the role of radionuclide techniques in the diagnosis, staging and follow-up of these tumors. METHODS: Eight patients (5 women, 3 men, age range 35-79 years; mean ± SD 56.1 ± 15.8 years) entered the study. In 4 patients, myasthenia gravis was the presenting symptom. 111In-DTPA-octreotide scan was performed within 3 weeks after contrast enhanced CT and/or MRI. Planar and tomographic images were acquired within 24 hours of the injection of 111 MBq OctreoScan. The scintigraphic results were defined in correlation with the histological findings. RESULTS: Histology revealed thymoma in 3 patients, thymic carcinoma in 1, insular carcinoma of presumably thymic origin in 1, thymic carcinoid in 1, and thymic hyperplasia in 2 patients. Two thymomas were at stage I, 1 thymoma and 1 thymic carcinoma at stage II, 1 insular carcinoma of presumably thymic origin at stage IV, and 1 thymic carcinoid at stage IV. OctreoScan consistently accumulated in primary and/or metastatic sites of thymic tumors while no radiotracer uptake was detected in the 2 patients with benign thymic hyperplasia. In 1 patient with a very large mediastinal mass (13 cm in largest diameter) and multiple metastatic deposits in the lungs, OctreoScan scintigraphy showed a large area of pathological uptake in the anterior mediastinum and a small area of focal uptake in the cervical-dorsal region of the right lung corresponding to a lymph node expressing somatostatin receptors. CONCLUSIONS: OctreoScan is avidly taken up by thymic tumors, enabling the diagnosis of these tumors and a better evaluation of their extension. It does not accumulate in thymic hyperplasia, thus allowing the differential diagnosis between these 2 pathological conditions. In patients affected by myasthenia gravis, OctreoScan scintigraphy can play an important role in characterizing thymic masses.

Unusual presentation of extranodal diffuse large B-cell lymphoma in a solid-organ recipient during long-term immunosuppressive treatment.

INTRODUCTION: Posttransplant lymphoproliferative disorders (PTLDs) refer to a group of diseases, including diffuse large B-cell lymphoma (DLBCL), that develop after solid organ transplantation or hematopoietic stem cell transplantation. Extranodal involvement in PTLDs is common. Reports about exclusive bone marrow involvement are rare. CASE DESCRIPTION: A 70-year-old woman, who had undergone kidney transplantation in 2018, was diagnosed with exclusively extranodal, Epstein-Barr virus-negative DLBCL, with bone marrow and spleen involvement, during long-term immunosuppression. She achieved complete remission with combined immunochemotherapy and temporary hold of immunosuppression. CONCLUSIONS: This case shows an uncommon clinical presentation of DLBCL, which was challenging to diagnose, being entirely extranodal. The favorable clinical course relied on timely diagnosis and a multidisciplinary approach. Long-term consequences of posttransplant immunosuppression require a high level of suspicion for an appropriate management, aimed at preserving the graft while eradicating the lymphoproliferative disorder.

Functional nuclear medicine imaging of medullary thyroid cancer.

Medullary thyroid cancer (MTC) originates from parafollicular C cells of the thyroid and accounts for 3-12% of all thyroid cancers. As opposed to other types of dedifferentiated thyroid tumours, MTC cells are highly functional, producing and secreting high amounts of calcitonin and carcinoembryonic antigen. As parafollicular C cells are of neural crest origin, MTC acts as a neuroendocrine tumour also and expresses somatostatin receptors. Although conventional radiological methods such as ultrasonography, computed tomography and magnetic resonance imaging are widely used in the primary diagnosis and staging, they often fail to localize the residual or recurrent disease because the majority of MTC recurrence presents as occult disease. Thus, owing to functional characteristics of MTC, functional imaging modalities of nuclear medicine play a major role in the diagnostic and therapeutic strategies for MTC. Among nuclear medicine modalities, Tc(V) -dimercaptosuccinic acid, In-octreotide and I/I-meta-iodobenzylguanidine are commonly used in the diagnostic and even more in postoperative work-up of MTC. Alternatively, F-fluorodeoxyglucose and other positron emission tomography radiopharmaceuticals such as F-fluorodopa or F-fluorodopamine as well as radiolabelled antibodies such as Tc/I/I anticarcinoembryonic antigen, antigastrin, and anticholecystokinin-B have promising results. Functional imaging has a great advantage for nuclear medicine techniques in the routine work-up of MTC patients and also has a wide use in experimental studies.

Diagnosis of infected total knee arthroplasty with anti-granulocyte scintigraphy: the importance of a dual-time acquisition protocol.

OBJECTIVE: To evaluate clinical efficacy of a dual-time acquisition protocol consisting of early 4 h and delayed 20-24 h imaging with anti-granulocyte scintigraphy (LeukoScan) in the diagnosis of infection in painful total knee arthroplasty (TKA). MATERIALS AND METHODS: Seventy-eight consecutive patients with TKA (12 bilateral) were prospectively enrolled in the study from August 2004 to July 2005. All the patients had clinical and biochemical suspicious of infection, except for the 12 patients with bilateral painless prosthesis who had no signs and symptoms of loosening and/or infection and were considered as controls. TKA prostheses had been implanted 4 months to 9.5 years before our studies. Forty-three patients were on antibiotic therapy at the moment of scintigraphic examination, and treatment was not discontinued. All patients underwent LeukoScan examination by performing both early 4 h and delayed 20-24 h imaging. In addition to planar imaging SPECT was performed in 18 cases. A decrease in radiotracer uptake from early to delayed LeukoScan imaging was interpreted as an unspecific finding (negative for infection), while an increasing uptake was interpreted as a positive finding for the presence of infection. Three-phase Tc-MDP bone scan was also routinely performed by standard technique. Sensitivity and specificity of early and delayed LeukoScan imaging were calculated. RESULTS: Sensitivity for early and delayed imaging were 92.7%, while specificity was 78.4% for early imaging and 100% for delayed imaging approach. SPECT imaging did not add any significant information as regard to specificity in our experience. Eight false positive early scans were correctly diagnosed as negative at delayed imaging. Three false negative results were recorded. Sensitivity and specificity were similar when patients were on or off antibiotic therapy. Imaging was negative in all 12 controls. CONCLUSIONS: Our results, based on a large group of patients, suggest that delayed LeukoScan imaging is important in identifying false positive results detect at early imaging. Thus, a dual-time, 4 h early and 20-24 h delayed LeukoScan imaging approach should be recommended to increase the diagnostic accuracy of the scintigraphy, with the exception of patients with a negative early LeukoScan examination, in whom the acquisition of delayed imaging appears unnecessary. In our experience, concomitant antibiotic therapy did not influence the diagnostic value of LeukoScan.

Antigranulocyte scintigraphy in infected hip prosthesis: the diagnostic importance of delayed 20-24-h imaging and semiquantitative analysis.

AIM: To evaluate clinical efficacy of a dual-time acquisition protocol, which included 4 and 20/24-h imaging with antigranulocyte antibody scintigraphy (LeukoScan) combined with semiquantitative analysis in the diagnosis of infection in painful hip prosthesis. METHODS: Sixty-seven consecutive patients with hip prosthesis were enrolled in this research project: 35 females, 32 males, mean age of 56.3 years. All patients had clinical and biochemical suspicious of infection. Each prosthesis had been implanted 3 months to 12 years before enrollment in this study. Twenty-four patients were on antibiotic therapy at the time of scintigraphy. Seven patients had bilateral hip prosthesis, one painful and the other painless: the seven painless prostheses were considered controls. LeukoScan examination was performed both at early (4 h) and delayed (20/24 h) times. The scintigraphic data were assessed both by visual and semiquantitative methods by three experienced nuclear medicine physicians blinded to clinical, laboratory and radiographic results. The uptake was graded visually by a 4-point scale: intense=3, moderate=2, mild=1 and absent=0. The semiquantitative analysis was obtained by a region of interest (ROI) analysis used in the anterior views to measure the ratio between the mean radioactivity in the prosthesis and the background radioactivity in the early and delayed images. An increase in the intensity of uptake of at least one scale-step at visual analysis and 20% at semiquantitative ROI analysis at the dual-time (early vs. delayed) LeukoScan was considered consistent with infection, whereas a stable or decreasing pattern was judged a negative result. Three-phase 99mTc-hydroxymethane diphosphonate bone scan was also performed routinely. Final diagnosis was determined at surgery and/or long-term clinical and imaging follow-up. RESULTS: At visual analysis, sensitivity for both early and delayed imaging was 94%, whereas specificity was 71% for early imaging and 83% for early and delayed imaging approach. At semiquantitative ROI analysis, sensitivity remained 94%, whereas specificity rose slightly to 73% for early imaging and to 90% for early and delayed imaging combined. Of note, four false-positive early scans were diagnosed correctly as negative on delayed imaging showing a decreasing pattern in uptake intensity. Sensitivity and specificity were similar whether patients were on or off antibiotic therapy. CONCLUSION: Our data show that early imaging LeukoScan is highly sensitive in evaluating septic prosthesis, but it is not optimally specific. Although the dual-time LeukoScan is capable of significantly increasing specificity for detecting infection. The semiquantitative ROI analysis further increased the specificity. Concomitant antibiotic treatment did not seem to influence the diagnostic efficacy of LeukoScan scintigraphy in detecting infected hip prosthesis.

Reconstruction parameters for 111In-pentetreotide SPECT: variability with respect to body weight and body region.

UNLABELLED: This study, which was based on a large series of consecutive patients imaged by (111)In-pentetreotide SPECT for a neuroendocrine tumor, evaluated variability in reconstruction parameters in relation to patient body weight and the body region imaged, looking for the possibility of standardizing such parameters. METHODS: One hundred twenty-four patients underwent (111)In-pentetreotide scintigraphy: 4- and 24-h whole-body and planar scans and a 24-h SPECT examination. All patients were injected with 140-150 MBq of (111)In-pentetreotide at least 1 wk after somatostatin analogs had been discontinued. SPECT images were systematically acquired at the levels of the head, chest, and abdomen. SPECT was performed using a dual-head gamma-camera with medium-energy collimators, step-and-shoot method, no circular orbit, a 64 x 64 matrix, and 30 s per view for a total of 64 views. Two reconstruction procedures were compared: the iterative method using 10 iterations and the filtered backprojection method using a Butterworth filter with different cutoffs and orders. RESULTS: Optimal SPECT images were obtained by applying the Butterworth filter. The reconstruction parameters could be standardized for the head and chest but were more variable for the abdomen, mainly because (111)In-pentetreotide is physiologically trapped in different intestinal areas and varies over time, especially in the liver, spleen, bowel, and urinary tract. CONCLUSION: Filtered backprojection using a Butterworth filter appears adequate for standardizing the reconstruction parameters for (111)In-pentetreotide SPECT of the head and chest. Processing of abdominal images is more operator-dependent. A 150-MBq dose of (111)In-pentetreotide is recommended when planning multiple SPECT acquisitions in the same patient.

FDG-PET detection of primary bone marrow large B-cell lymphoma in a patient with hairy cell leukemia.

We describe a case of hairy cell leukaemia (HCL) coexistent with non-Hodgkin's lymphoma (NHD). This combination is reported to be extremely rare with no clear demonstration of the clonal relationship between the two conditions. After a previous failure of purine analogue therapy, our patient was successfully treated with rituximab resulting in normalisation of blood cell count cessation of blood transfusion and negative iliac crest biopsy. Unfortunately, the patient developed intense and persistent bone pain during the 1(st) line treatment for HCL. Skeletal X-rays, neck-thorax-abdomen CT scan and repeated bone MRI were unremarkable and bone scintigraphy showed non-specific changes. Laboratory examinations were normal. To better evaluate bone scintigraphy results, we finally performed FDG-PET/CT, which showed multiple foci of intense abnormal radiotracer uptake involving the bone marrow. An FDG-PET/CT guided bone marrow biopsy showed primary bone marrow diffuse large B-cell lymphoma (LBCL). Despite 2(nd) and 3(rd) line treatment, the patient died shortly after for central nervous system involvement by NHD. The role of FDG-PET/CT in identifying bone and bone marrow localization of NHD is reviewed and an earlier use is suggested in poorly understood bone pain.

The prognostic value of 18F-FDG PET-CT in the management of Hodgkin's lymphoma: preliminary results of a prospective study.

BACKGROUND: To date, Hodgkin's lymphoma (HL) patients have achieved long-term survival of more than 80%. Unfortunately, longer follow-up has shown serious adverse effects of the treatments used. For this reason, therapeutic strategies are becoming more tailored to the individual patient s prognosis. Pre-treatment risk factors for early-stage and advanced-stage HL are well known indicators of prognosis. Recently, early interim (18)F-FDG PET has been shown as a strong and independent predictor of progression-free survival in HL. Our aim was to assess response to therapy by repeating (18)F-FDG-PET/CT after four and six chemotherapy cycles. MATERIAL AND METHODS: We evaluated 21 consecutive patients affected by (HL) and presenting for assessment over a period of three years. All patients underwent initial staging with (18)F-FDG-PET/CT along with standard staging procedures. We tailored an individual treatment plan dependent on pre-treatment risk factors and initial (18)F-FDG-PET/CT. With the aim of the best definition of response to treatment, we repeated (18)F-FDG-PET/CT after two (FDG-PET 2), four (FDG-PET 4) and six (FDG-PET 6) chemotherapy cycles. Chemotherapy was typically given for four cycles in early disease stages and was prolonged to six to eight cycles in advanced disease stages, depending on PET findings. RESULTS: Our results showed a strong negative predictive value in detecting responders in early stage HL and a positive predictive value in advanced-stage patients. Clinical stage, extra-nodal sites and the positivity of the (18)F-FDG-PET/CT performed during chemotherapy were also noted as strong determinants of response to treatment. Moreover, in our series the (18)F-FDG-PET/CT data obtained after only two chemotherapy cycles (FDG-PET 2) were the same of those obtained after FDG-PET 4 and FDG-PET 6 controls. CONCLUSION: The preliminary data of the present study confirm those of previous published studies about the negative predictive value of (18)F-FDG-PET/CT performed after four and six chemotherapy cycles, which contributed to the decision to stop treatment and to avoid radiotherapy in HL patients. Nonetheless, our preliminary data seems to suggest that only the (18)F-FDG-PET/CT performed after two cycles of chemotherapy (FDG-PET 2) is able to provide the same prognostic information of the FDG-PET 4 and FDG-PET 6 earlier.

Role of 18F-FDG-PET and PET/CT imaging in thyroid cancer.

In patients affected by differentiated thyroid cancer (DTC), the lacking of 131Iodine trapping by metastatic tissue does not allow 131Iodine whole body scintigraphy to visualize matastatic spread as well as the use of 131Iodine therapy to cure such metastatic spread. Prognosis of 131Iodine-negative DTC metastasis, so-called non-functioning metastasis, is significantly worst. In these patients an early diagnosis of non-functioning metastasis and their surgical extirpation remains the optimal therapeutic approach. In this view, a high sensitive localizing imaging different form 131Iodine whole body scintigraphy is required. Ultrasonography is characterized by a relatively high sensitivity in these patients but it is highly operator-dependent and, moreover, it can be used to explore neck alone. Computed tomography (CT) scan and magnetic resonance (MR) imaging are characterized by a relatively low sensitivity even if they are useful to provide the surgeon with anatomical information of the operating basin. Various tumor-seeking radiotracers have been proposed, mainly using SPECT as 201Thallium, 99mTc-Sestamibi and 99mTc-Tetrofosmin with good results. Even more favorable results have been reported with some positron radiotracers, mainly the 18F-FDG with PET and more recently with PET/CT tomographs. The typical indication to performing with examination is the DTC patient previously treated by total thyroidectomy and 131Iodine ablative therapy, with increased serum thyroglobulin (Tg) or anti-thyroglobulin (TgAb) antibodies during follow-up but with negative 131Iodine whole body scintigraphy even obtained after high, therapeutic 131Iodine doses. Several studies in literature have reported high sensitivity (up to 85%) and specificity (up to 95%) of FDG-PET in metastatic DTC patients. The integrated PET/CT fusion imaging systems, seem able to provide some additional advantages over PET alone, mainly related to a better anatomical localization of the hypermetabolic metastatic lesions. A change in the management of DTC patients affected by non-functioning metastatic spread not visualized by other imaging techniques has been reported in 30% of patients. Lastly, the role of PET and PET/CT fusion imaging systems seem to be promising also in patients affected by medullary thyroid carcinoma (MTC), especially for the detection of neck and mediastinal lesions, with a sensitivity superior to the other currently available imaging methods, however the data reported on medullary cancer are little and further studies are needed to elucidate the preliminary promising results.

Comparison of different thyroid committed doses in radioiodine therapy for Graves' hyperthyroidism.

Despite vast worldwide experience in the use of 131I for treating Graves' disease (GD), no consensus of opinion exists concerning the optimal method of dose calculation. In one of the most popular equations, the administered (131)I dose is directly proportional to the estimated thyroid gland volume and inversely proportional to the measured 24-hour radioiodine uptake. In this study, we compared the efficiency of different tissue-absorbed doses to induce euthyroidism or hypothyroidism within 1 year after radioiodine therapy in GD patients. The study was carried out in 134 GD patients (age, 53 +/- 14 year; range, 16-82 year; thyroid volume, 28 +/- 18 mL; range, 6-95 mL; average 24-hour thyroid uptake, 72%) treated with (131)I therapy. The average radioiodine activity administered to patients was 518 +/- 226 MBq (range, 111-1110). The corresponding average thyroid absorbed dose, calculated by a modified Medical Internal Radiation Dose (MIRD) equation was 376 +/- 258 Gy (range, 99-1683). One year after treatment, 58 patients (43%) were hypothyroid, 57 patients (43%) were euthyroid, and 19 patients (14%) remained hyperthyroid. The patients were divided into 3 groups: 150 Gy (n = 32), 300 Gy (n = 58) and >300 Gy (n = 44). No significant difference in the rate of recurrent hyperthyroidism was found among the 3 groups (150 Gy: 15%; 300 Gy: 14%; and > or =300 Gy: 14%; chi-square test, p = 0.72). Whereas, the rate of hypothyroidism in the 3 groups was significantly correlated with the dose (150 Gy: 30%; 300 Gy: 46%; >300 Gy: 71%; chi-square test, p = 0.0003). The results obtained in this study show no correlation between dose and outcome of radioiodine therapy (in terms of persistent hyperthyroidism) for thyroid absorbed doses > or =150 Gy, while confirming the relation between the thyroid absorbed dose and the incidence of hypothyroidism in GD patients.

Additional value of FDG-PET/CT in management of "solitary" liver metastases: preliminary results of a prospective multicenter study.

BACKGROUND AND AIM: The most common malignancy affecting the liver is metastasis from a wide variety of tumors, particularly those of gastrointestinal origin. Successful surgical removal of a solitary liver metastasis may significantly extend survival and optimal preoperative assessment in this regard is a mandatory prerequisite for proper patient selection. The addition of positron emission tomography/computed tomography (PET/CT) to other more conventional imaging procedures (e.g., ultrasound (US), CT, and magnetic resonance) has the potential to greatly improve the selection process by the combination of high-resolution anatomy afforded by CT directly combined with the functional scintigraphic map of intra- and extrahepatic lesions depicted by 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-PET. In this study, we assess the additional value of PET/CT in the management strategy of patients with solitary liver metastasis from colorectal and other cancers identified by conventional imaging methods. METHODS: We evaluated 43 consecutive patients (17 males, 26 females, mean age 53 +/- 6 years) with known solitary liver metastasis. This sample consisted of 18 patients with colorectal cancer, 15 with nonsmall cell lung cancer, six with breast carcinoma, and four ovarian cancers. In addition to contrast-enhanced CT and US, all patients were studied with FDG-PET/CT before surgery. PET/CT was performed within 3 weeks of the initial diagnosis and the scans were read by two experienced radiologists/nuclear medicine specialists blinded to the clinical data. A final diagnosis was obtained at surgery in 31 patients, by fine needle biopsy in five, and long-term clinical, biochemical, and follow-up imaging in seven patients. RESULTS: In 12 out of 43 patients (28%), PET/CT resulted in restaging disease and a change in therapy. Twenty-two of 31 patients with confirmed solitary liver lesions (71%) were disease-free, eight of 31 (26%) developed a new recurrence, and one of 31 (3%) died from disease progression over a 17 +/- 6-month follow-up interval. Nine of 12 patients (75%) with multiple metastases demonstrated by FDG-PET/CT were alive with disease and three of 12 (25%) deceased due to disease progression (p < 0.01) over a 17 +/- 6-month follow-up interval. CONCLUSION: The addition of FDG-PET/CT to the routine assessment of patients with liver metastasis has a significant impact on disease staging and selection of suitable candidates for solitary liver metastasis resection and outcome.

The role of dual-time combined 18-fluorodeoxyglucose positron emission tomography and computed tomography in the staging and restaging workup of locally advanced rectal cancer, treated with preoperative chemoradiation therapy and radical surgery.

PURPOSE: In patients with locally advanced rectal cancer (LARC) staging and, after preoperative chemo-radiation therapy (CRT), restaging workup could be useful to tailor therapeutic approaches. Fluorine-18-fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) is a promising tool for monitoring the effect of antitumor therapy. This study was aimed to evaluate the possible role of dual time sequential FDG-PET scans in the staging and restaging workup of LARC. METHODS AND MATERIALS: Eighty-seven consecutive patients with LARC were enrolled. CRT consisted of external-beam intensified radiotherapy (concurrent boost), with concomitant chemotherapy PVI 5-FU (300 mg/m(2)/day) followed 8-10 weeks later by surgery. All patients underwent [(18)F]FDG-PET/CT before and 5-6 weeks later after the completion of CRT. Measurements of FDG uptake (SUV(max)), and percentage of SUV(max) difference (Response Index = RI) between pre- and post-CRT [(18)F]FDG-PET scans were evaluated. RESULTS: Six of 87 patients were excluded due to protocol deviation. Following CRT, 40/81 patients (49%) were classified as responders according to Mandard's criteria (TRG1-2). The mean pre-CRT SUV(max) was significantly higher than post-CRT (15.8, vs 5.9; p < 0.001). The mean RI was significantly higher in responders than in nonresponder patients (71.3% vs 38%; p = 0.0038). Using a RI cut-off of 65% for defining response to therapy, the following parameters have been obtained: 84.5% sensitivity, 80% specificity, 81.4% positive predictive value, 84.2% negative predictive value, and 81% overall accuracy. CONCLUSION: These results suggest the potential role of [(18)F]FDG-PET in the restaging workup after preoperative CRT in LARC. RI seems the best predictor to identify CRT response.

Slow dynamic lymphoscintigraphy is not a reliable predictor of sentinel-node negativity in cutaneous melanoma.

We reviewed data from 160 consecutive patients (89 M/71 F; 53.5 [range, 9-88] years) who had under-gone lymphoscintigraphy and sentinel lymph node biopsy (SNB) in our hospital for histologically proven cutaneous malignant melanoma (CMM) (located on the upper limb: 33; lower limb: 57; trunk: 44; and head and neck: 26 patients), with a Breslow index > 1 mm and without clinical or radiologic evidence of metastatic spread. Colloidal (99m)Tc-rhenium sulfide (36-76 MBq) was injected intradermally in the four quadrants around the tumorectomy scar, followed by dynamic acquisition and static imaging. SN(s) were identified in 157 patients (overall identification rate, 98%). Fast (< 20 minutes), intermediate (20-30 minutes), or slow (> 30 minutes) lymphatic drainage was observed, respectively, in 122 (78%), 24 (15%), or 11 (7%) cases. Overall malignancy rate was 15%, respectively found in 19 (16%), 2 (8%), and 2 (18 %) patients with fast, intermediate, or slow drainage. No statistical difference between SN-positivity rates of patients with fast (19/122 = 16%) versus intermediate or slow drainage (4/35 = 11.4%) was observed (p = 0.69). Therefore, lymphoscintigraphic SN appearance time in CMM patients is unable both to predict SN metastasis and spare them from undergoing SN excision.

Sequential FDG-PET/CT reliably predicts response of locally advanced rectal cancer to neo-adjuvant chemo-radiation therapy.

PURPOSE: Prediction of rectal cancer response to preoperative, neo-adjuvant chemo-radiation therapy (CRT) provides the opportunity to identify patients in whom a major response is expected and who may therefore benefit from alternative surgical approaches. Traditional morphological imaging techniques are effective in defining tumour extension in the initial diagnostic and staging work-up, but perform poorly in distinguishing residual neoplastic tissue from scarring post CRT, when restaging the patient before surgery. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is a promising tool for monitoring the effect of anti-tumour therapy. The aim of this study was to prospectively assess the value of sequential FDG-PET scans in predicting the response of locally advanced rectal cancer to neo-adjuvant CRT. METHODS: Forty-four consecutive patients with locally advanced (cT3-4) primary rectal cancer and four patients with pelvic recurrence of rectal cancer were enrolled in this prospective study. Treatment consisted of external beam intensified radiotherapy (50 Gy to the posterior pelvis, 56 Gy to the tumour), chemotherapy (in most cases PVI 5-FU at 300 mg/m(2) per day) and, 8-10 weeks later, surgery with curative intent. All patients underwent FDG-PET/CT both before CRT and 5-6 weeks after completing CRT. One patient died before surgery because of acute myocardial infarction, and was therefore excluded from further analysis. Semi-quantitative measurements of FDG uptake (SUV(max)), absolute difference (DeltaSUV(max)) and percent SUV(max) difference (Response Index, RI) between pre- and post-CRT PET scans were considered. Results were correlated with pathological response, assessed both by histopathological staging of the surgical specimens (pTNM) and by the tumour regression grade (TRG) according to Mandard's criteria (patients with TRG1-2 being defined as responders and patients with TRG3-5 as non-responders). RESULTS: Following neo-adjuvant CRT, of the 45 patients submitted to surgery, 23 (51.1%) were classified as responders according to Mandard's criteria (8 TRG1 and 15 TRG2), while the remaining 22 (48.9%) were non-responders (9 TRG3 and 13 TRG4-5). Considering all patients, the mean pre-CRT SUV(max) was 15.6, significantly higher than the mean value of 5.4 post CRT (p < 0.001). Nevertheless, when stratifying patients according to response to CRT (using Mandard's criteria), the mean RI was significantly higher in responders than in non-responders (75.9% versus 46.9%,p = 0.0015). Using a 66.2% SUV(max) decrease as the cut-off value (identified by ROC analysis) for defining response to therapy, the following parameters were obtained: 79.2% specificity, 81.2% sensitivity, 77% positive predictive value, 89% negative predictive value and 80% overall accuracy. CONCLUSION: The results suggest the potential utility of FDG-PET as a complementary diagnostic and prognostic procedure in the assessment of neo-adjuvant CRT response of locally advanced rectal cancer. DeltaSUV(max) and RI seem the best predictors of CRT response.