The 68Ga/177Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUVmax values and absorbed dose estimates.

INTRODUCTION: A targeted theragnostic approach based on increased expression of prostate-specific membrane antigen (PSMA) on PC cells is an attractive treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: Ten consecutive mCRPC patients were selected for 177Lu-PSMA617 therapy on the basis of PSMA-targeted 68Ga-PSMA-HBED-CC PET/CT diagnosis showing extensive and progressive tumour load. Following dosimetry along with the first therapy cycle restaging (68Ga-PSMA-HBED-CC and 18F-NaF PET/CT) was performed after 2 and 3 therapy cycles (each 6.1 ± 0.3 GBq, range 5.4-6.5 GBq) given intravenously over 30 minutes, 9 ± 1 weeks apart. PET/CT scans were compared to 177Lu-PSMA617 24-hour whole-body scans and contrast-enhanced dual-phase CT. Detailed comparison of SUVmax values and absorbed tumour doses was performed. RESULTS: 177Lu-PSMA617 dosimetry indicated high tumour doses for skeletal (3.4 ± 1.9 Gy/GBq; range 1.1-7.2 Gy/GBq), lymph node (2.6 ± 0.4 Gy/GBq; range 2.3-2.9 Gy/GBq) as well as liver (2.4 ± 0.8 Gy/GBq; range 1.7-3.3 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 18 ± 0.3 GBq. Three patients showed partial remission, three mixed response, one stable and three progressive disease. Decreased 177Lu-PSMA617 and 68Ga-PSMA-HBED-CC uptake (mean SUVmax values 20.2 before and 15.0 after 2 cycles and 11.5 after 3 cycles, p < 0.05) was found in 41/54 skeletal lesions, 12/13 lymph node metastases, 3/5 visceral metastases and 4/4 primary PC lesions. CONCLUSION: Due to substantial individual variance, dosimetry is mandatory for a patient-specific approach following 177Lu-PSMA617 therapy. Higher activities and/or shorter treatment intervals should be applied in a larger prospective study.

Early dynamic imaging in 68Ga- PSMA-11 PET/CT allows discrimination of urinary bladder activity and prostate cancer lesions.

PURPOSE: PET/CT with 68Ga-labelled prostate-specific membrane antigen (PSMA)-ligands has been proven to establish a promising imaging modality in the work-up of prostate cancer (PC) patients with biochemical relapse. Despite a high overall detection rate, the visualisation of local recurrence may be hampered by high physiologic tracer accumulation in the urinary bladder on whole body imaging, usually starting 60 min after injection. This study sought to verify whether early dynamic 68Ga-PSMA-11 (HBED-CC)PET/CT can differentiate pathologic PC-related tracer uptake from physiologic tracer accumulation in the urinary bladder. METHODS: Eighty consecutive PC patients referred to 68Ga -PSMA-11 PET/CT were included in this retrospective analysis (biochemical relapse: n = 64; primary staging: n = 8; evaluation of therapy response/restaging: n = 8). In addition to whole-body PET/CT acquisition 60 min post injection early dynamic imaging of the pelvis in the first 8 min after tracer injection was performed. SUVmax of pathologic lesions was calculated and time-activity curves were generated and compared to those of urinary bladder and areas of physiologic tracer uptake. RESULTS: A total of 55 lesions consistent with malignancy on 60 min whole body imaging exhibited also pathologic 68Ga-PSMA-11 uptake during early dynamic imaging (prostatic bed/prostate gland: n = 27; lymph nodes: n = 12; bone: n = 16). All pathologic lesions showed tracer uptake within the first 3 min, whereas urinary bladder activity was absent within the first 3 min of dynamic imaging in all patients. Suvmax was significantly higher in PC lesions in the first 6 min compared to urinary bladder accumulation (p < 0.001). In the subgroup of PC patients with biochemical relapse the detection rate of local recurrence could be increased from 20.3 to 29.7%. CONCLUSIONS: Early dynamic imaging in 68Ga-PSMA-11 PET/CT reliably enables the differentiation of pathologic tracer uptake in PC lesions from physiologic bladder accumulation. Performance of early dynamic imaging in addition to whole body imaging 60 min after tracer injection might improve the detection rate of local recurrence in PC patients with biochemical relapse referred for 68Ga-PSMA-11 PET/CT.

68Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour.

PURPOSE: Prostate cancer (PC) cells typically show increased expression of prostate-specific membrane antigen (PSMA), which can be visualized by 68Ga-PSMA-11 PET/CT. The aim of this study was to assess the intensity of 68Ga-PSMA-11 uptake in the primary tumour and metastases in patients with biopsy-proven PC prior to therapy, and to determine whether a correlation exists between the primary tumour-related 68Ga-PSMA-11 accumulation and the Gleason score (GS) or prostate-specific antigen (PSA) level. METHODS: Ninety patients with transrectal ultrasound biopsy-proven PC (GS 6-10; median PSA: 9.7 ng/ml) referred for 68Ga-PSMA-11 PET/CT were retrospectively analysed. PET images were analysed visually and semiquantitatively by measuring the maximum standardized uptake value (SUVmax). The SUVmax of the primary tumour and pathologic lesions suspicious for lymphatic or distant metastases were then compared to the physiologic background activity of normal prostate tissue and gluteal muscle. The SUVmax of the primary tumour was assessed in relation to both PSA level and GS. RESULTS: Eighty-two patients (91.1%) demonstrated pathologic tracer accumulation in the primary tumour that exceeded physiologic tracer uptake in normal prostate tissue (median SUVmax: 12.5 vs. 3.9). Tumours with GS of 6, 7a (3+4) and 7b (4+3) showed significantly lower 68Ga-PSMA-11 uptake, with median SUVmax of 5.9, 8.3 and 8.2, respectively, compared to patients with GS >7 (median SUVmax: 21.2; p < 0.001). PC patients with PSA ≥10.0 ng/ml exhibited significantly higher uptake than those with PSA levels <10.0 ng/ml (median SUVmax: 17.6 versus 7.7; p < 0.001). In 24 patients (26.7%), 82 lymph nodes with pathologic tracer accumulation consistent with metastases were detected (median SUVmax: 10.6). Eleven patients (12.2%) revealed 55 pathologic osseous lesions suspicious for bone metastases (median SUVmax: 11.6). CONCLUSIONS: The GS and PSA level correlated with the intensity of tracer accumulation in the primary tumours of PC patients on 68Ga-PSMA-11 PET/CT. As PC tumours with GS 6+7 and patients with PSA values ≤10 ng/ml showed significantly lower 68Ga-PSMA-11 uptake, 68Ga-PSMA-11 PET/CT should be preferentially applied for primary staging of PC in patients with GS >7 or PSA levels ≥10 ng/ml.

Early PET imaging with [68]Ga-PSMA-11 increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence.

PURPOSE: PET/CT using 68Ga-labelled prostate-specific membrane antigen PSMA-11 (HBEDD-CC) has emerged as a promising imaging method in the diagnostic evaluation of prostate cancer (PC) patients with biochemical recurrence. However, assessment of local recurrence (LR) may be limited by intense physiologic tracer accumulation in the urinary bladder on whole-body scans, normally conducted 60 min post-tracer injection (p.i.). It could be shown on early dynamic imaging studies that 68Ga-PSMA-11 uptake in PC lesions occurs earlier than tracer accumulation in the urinary bladder. This study aims to investigate whether early static PET acquisition increases detection rate of local recurrence on 68Ga-PSMA-11 PET/CT in comparison to PET imaging 60 min p.i.. METHODS: 203 consecutive PC patients with biochemical failure referred to 68Ga-PSMA-11 PET/CT were analysed retrospectively (median prostate specific antigen (PSA) value: 1.44 ng/ml). In addition to whole-body PET/CT scans 60 min p.i., early static imaging of the pelvis was performed, starting at a median time of 283 s p.i. (range: 243-491 s). Assessment was based on visual analysis and calculation of maximum standardized uptake value (SUVmax) of pathologic lesions present in the pelvic area found on early PET imaging and on 60 min-PET scans. RESULTS: 26 patients (12.8%) were judged positive for LR on PET scans 60 min p.i. (median SUVmax: 10.8; range: 4.7-40.9), whereas 50 patients (24.6%) revealed a lesion suggestive of LR on early PET imaging (median SUVmax: 5.9; range: 2.9-17.6), resulting in a significant rise in detection rate (p < 0.001). Equivocal findings on PET scans 60 min p.i. decreased significantly with the help of early imaging (15.8% vs. 4.5% of patients; p < 0.001). Tracer activity in the urinary bladder with a median SUVmax of 8.2 was present in 63 patients on early PET scans (31.0%). However, acquisition starting time of early PET scans differed significantly in the patient groups with and without urinary bladder activity (median starting time of 321 vs. 275 s p.i.; range: 281-491 vs. 243-311 s p.i.; p < 0.001). Median SUVmax value of lesions suggestive of LR on early images was significantly higher in comparison to gluteal muscle, inguinal vessels and seminal vesicle/anastomosis (median SUVmax: 5.9 vs. 1.9, 4.0 and 2.4, respectively). CONCLUSIONS: Performance of early imaging in 68Ga-PSMA-11 PET/CT in addition to whole-body scans 60 min p.i. increases the detection rate of local recurrence in PC patients with biochemical recurrence. Acquisition of early PET images should be started as early as 5 min p.i. in order to avoid disturbing tracer activity in the urinary bladder occuring at a later time point.

Direct comparison of (68)Ga-DOTA-TOC and (18)F-FDG PET/CT in the follow-up of patients with neuroendocrine tumour treated with the first full peptide receptor radionuclide therapy cycle.

PURPOSE: To determine the value of (68)Ga-DOTA-TOC and (18)F-FDG PET/CT for initial and follow-up evaluation of patients with neuroendocrine tumour (NET) treated with peptide receptor radionuclide therapy (PRRT). METHODS: We evaluated 66 patients who had histologically proven NET and underwent both PRRT and three combined (68)Ga-DOTA-TOC and (18)F-FDG PET/CT studies. (68)Ga-DOTA-TOC PET/CT was performed before PRRT, 3 months after completion of PRRT and after a further 6 - 9 months. (18)F-FDG PET/CT was done within 2 months of (68)Ga-DOTA-TOC PET/CT. Follow-up ranged from 11.8 to 80.0 months (mean 34.5 months). RESULTS: All patients were (68)Ga-DOTA-TOC PET-positive initially and at follow-up after the first full PRRT cycle. Overall, 62 of the 198 (18)F-FDG PET studies (31 %) were true-positive in 38 of the 66 patients (58 %). Of the 66 patients, 28 (5 grade 1, 23 grade 2) were (18)F-FDG-negative initially and during follow-up (group 1), 24 (5 grade 1, 13 grade 2, 6 grade 3) were (18)F-FDG-positive initially and during follow-up (group 2), 9 patients (2 grade 1, 6 grade 2, 1 grade 3) were (18)F-FDG-negative initially but (18)F-FDG-positive during follow-up (group 3), and 5 patients (all grade 2) were (18)F-FDG-positive initially but (18)F-FDG-negative during follow-up (group 4).(18)F-FDG PET showed more and/or larger metastases than (68)Ga-DOTA-TOC PET in five patients of group 2 and four patients of group 3, all with progressive disease. In three patients with progressive disease who died during follow-up tumour SUVmax increased by 41 - 82 % from the first to the last follow-up investigation. CONCLUSION: In NET patients, the presence of (18)F-FDG-positive tumours correlates strongly with a higher risk of progression. Initially, patients with (18)F-FDG-negative NET may show (18)F-FDG-positive tumours during follow-up. Also patients with grade 1 and grade 2 NET may have (18)F-FDG-positive tumours. Therefore, (18)F-FDG PET/CT is a complementary tool to (68)Ga-DOTA-TOC PET/CT with clinical relevance for molecular investigation.

Accuracy and feasibility of three different methods for software-based image fusion in whole-body PET and CT.

BACKGROUND: Even as PET/CT provides valuable diagnostic information in a great number of clinical indications, availability of hybrid PET/CT scanners is mainly limited to clinical centers. A software-based image fusion would facilitate combined image reading of CT and PET data sets if hardware image fusion is not available. To analyze the relevance of retrospective image fusion of separately acquired PET and CT data sets, we studied the accuracy, practicability and reproducibility of three different image registration techniques. METHODS: We evaluated whole-body 18F-FDG-PET and CT data sets of 71 oncologic patients. Images were fused retrospectively using Stealth Station System, Treon (Medtronic Inc., Louisville, CO, USA) equipped with Cranial4 Software. External markers fixed to a vacuum mattress were used as reference for exact repositioning. Registration was repeated using internal anatomic landmarks and Automerge software, assessing accuracy for all three methods, measuring distances of liver representation in CT and PET with reference to a common coordinate system. RESULTS: On first measurement of image fusions with external markers, 53 were successful, 16 feasible and 2 not successful. Using anatomic landmarks, 42 were successful, 26 feasible and 3 not successful. Using Automerge Software only 13 were successful. The mean distance between center points in PET and CT was 7.69±4.96 mm on first, and 7.65±4.2 mm on second measurement. Results with external markers correlate very well and inaccuracies are significantly lower (P<0.001) than results using anatomical landmarks (10.38±6.13 mm and 10.83±6.23 mm). Analysis revealed a significantly faster alignment using external markers (P<0.001). CONCLUSIONS: External fiducials in combination with immobilization devices and breathing protocols allow for highly accurate image fusion cost-effectively and significantly less time, posing an attractive alternative for PET/CT interpretation when a hybrid scanner is not available.

Multiparametric PET imaging in thyroid malignancy characterizing tumour heterogeneity: somatostatin receptors and glucose metabolism.

PURPOSE: Radiolabelled somatostatin (SST) analogues have proven useful in diagnosing tumours positive for SST receptor (SSTR). As different subtypes of SSTR are expressed on the tumour cell surface, the choice of appropriate therapeutic SST analogue is crucial. We evaluated the SSTR status of thyroid cancer patients who had signs of progressive disease comparing different SSTR ligands for PET imaging to evaluate possible further therapeutic options. METHODS: PET with (68)Ga-radiolabelled SSTR ligands DOTA lanreotide (DOTA-LAN), DOTA-Tyr(3) octreotide (DOTA-TOC) and (18)F-FDG was performed in 31 patients with thyroid cancer (TC). These 31 patients comprised 18 with radioiodine non-avid differentiated TC (DTC) including 6 papillary TC (PTC), 8 follicular TC (FTC) and 4 oxyphilic TC (oxyTC), 5 with anaplastic TC (ATC), and 8 with medullary TC (MTC). The PET results were compared in a region-based evaluation. RESULTS: All patients underwent a PET study with (68)Ga-DOTA-LAN, 28 patients with (68)Ga-DOTA-TOC and 28 patients with (18)F-FDG. A lack of SSTR expression was found in 13 of the 31 patients (42%) with negative results with both SSTR tracers in 12 patients. Ambiguous results with both SSTR tracers were observed in one patient. High tracer uptake in SSTR PET images was seen in seven DTC patients (39%; two PTC, three FTC, two oxyTC), in four ATC patients (80%) and in six MTC patients (75%). Lesions showing aerobic glycolysis on (18)F-FDG PET were found in 24 of 28 patients (86%) with corresponding positive results with (68)Ga-DOTA-LAN in 35% and with (68)Ga-DOTA-TOC in 29%. CONCLUSION: The heterogeneous SSTR profile of TC tumour lesions needs to be evaluated using different SSTR PET tracers to characterize more closely the SSTR subtype affinities in patients with progressive TC in order to further stratify therapy with SSTR therapeutics.

(68)Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate?

PURPOSE: To assess the association between PSA levels, PSA kinetics and other factors and a pathological (68)Ga-PSMA PET/CT scan in patients with recurrent prostate cancer (rPCa) with biochemical relapse (BR) after radical therapy. METHODS: Seventy consecutive rPCA patients referred for (68)Ga-PSMA PET/CT, matching all the following criteria, were retrospectively evaluated: (a) previous radical prostatectomy or primary radiotherapy with curative intent; (b) BR or persisting high PSA levels after primary treatment; and (c) complete clinical and imaging information. The mean ± SD PSA level was 3.5 ± 5.3 ng/mL (median 1.7, range 0.2 - 32.2 ng/mL), the mean ± SD PSA doubling time (PSAdt) was 6.5 ± 5.5 months (median 5.5, range 1.3 - 31.6 months), and the mean ± SD PSA velocity was 7.9 ± 20.5 (median 2.1, range 0.2 - 147.5 ng/mL/year). Statistical analysis was performed to assess which factors were associated with the detection of rPCa on (68)Ga-PSMA PET/CT. RESULTS: (68)Ga-PSMA PET/CT was positive in 52 of 70 patients (74.2%). In 30 patients (42.8%) lesions limited to the pelvis were detected. Distant lesions were observed in 8 of patients (11.4%). Local plus systemic lesions were detected in 14 patients (20%). PSA level (p = 0.017) and PSAdt (p = 0.0001) were significantly different between PET-positive patients (higher PSA level, shorter PSAdt) and PET-negative patients (lower PSA, longer PSAdt). ROC analysis showed that PSAdt 6.5 months and PSA 0.83 ng/mL were optimal cut-off values. In multivariate analysis PSAdt was associated with (68)Ga-PSMA PET/CT positivity. (68)Ga-PSMA PET/CT was positive in 17 of 20 patients (85%) with PSA <2 ng/mL and PSAdt <6.5 months, and in 3 of 16 patients (18.7%) with PSA <2 ng/mL and PSAdt ≥6.5 months. CONCLUSION: The great potential of (68)Ga-PSMA PET/CT in patients with rPCa and BR was confirmed. PSA and PSAdt were valuable predictors of pathological (68)Ga-PSMA PET/CT findings.

Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr 3-octreotide positron emission tomography and 123I-metaiodobenzylguanidine.

PURPOSE: (68)Ga-DOTA-Tyr(3)-octreotide positron emission tomography ((68)Ga-DOTA-TOC PET) has proven to be superior to (111)In-DTPA-D-Phe(1)-octreotide ((111)In-octreotide) planar scintigraphy and SPECT imaging in neuroendocrine tumours (NETs). Because of these promising results, we compared the accuracy of (123)I-metaiodobenzylguanidine ((123)I-MIBG) imaging with PET in the diagnosis and staging of metastatic phaeochromocytoma and neuroblastoma, referring to radiological imaging as reference standard. METHODS: Three male and eight female patients (age range 3 to 68 years) with biochemically and histologically proven disease were included in this study. Three male and three female patients were suffering from phaeochromocytoma, and five female patients from neuroblastoma. Comparative evaluation included morphological imaging with CT or MRI, functional imaging with (68)Ga-DOTA-TOC PET and (123)I-MIBG imaging. Imaging results were analysed on a per-patient and on a per-lesion basis. RESULTS: On a per-patient basis, both (68)Ga-DOTA-TOC and (123)I-MIBG showed a sensitivity of 100%, when compared with anatomical imaging. In phaeochromocytoma patients, on a per-lesion basis, the sensitivity of (68)Ga-DOTA-TOC was 91.7% and that of (123)I-MIBG was 63.3%. In neuroblastoma patients, on a per-lesion basis, the sensitivity of (68)Ga-DOTA-TOC was 97.2% and that of (123)I-MIBG was 90.7%. Overall, in this patient cohort, (68)Ga-DOTA-TOC PET identified 257 lesions, anatomical imaging identified 216 lesions, and (123)I-MIBG identified only 184 lesions. In this patient group, the overall sensitivity of (68)Ga-DOTA-TOC PET on a lesion basis was 94.4% (McNemar p<0.0001) and that of (123)I-MIBG was 76.9% (McNemar p<0.0001). CONCLUSION: Our analysis in this relatively small patient cohort indicates that (68)Ga-DOTA-TOC PET may be superior to (123)I-MIBG gamma-scintigraphy and even to the reference CT/MRI technique in providing particularly valuable information for pretherapeutic staging of phaeochromocytoma and neuroblastoma.

68Ga-DOTA-Tyr3-octreotide PET for assessing response to somatostatin-receptor-mediated radionuclide therapy.

UNLABELLED: (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide (DOTA-TOC) PET has proven its usefulness in the diagnosis of patients with neuroendocrine tumors. Radionuclide therapy ((90)Y-DOTA-TOC or (177)Lu-DOTA-octreotate) is a choice of treatment that also requires an accurate diagnostic modality for early evaluation of treatment response. Our study compared (68)Ga-DOTA-TOC PET with CT or MRI using the Response Evaluation Criteria in Solid Tumors. Furthermore, standardized uptake values (SUVs) were calculated and compared with treatment outcome. METHODS: Forty-six patients (29 men, 17 women; age range, 34-84 y) with advanced neuroendocrine tumors were investigated before and after 2-7 cycles of radionuclide therapy. Long-acting somatostatin analogs were not applied for at least 6 wk preceding the follow-up. Data were acquired with a dedicated PET scanner. Emission image sets were acquired at 90-100 min after injection. (68)Ga-DOTA-TOC PET images were visually interpreted by 2 experienced nuclear medicine physicians. For comparison, multislice helical CT scans and 1.5-T MRI scans were obtained. Attenuation-corrected PET images were used to determine SUVs. Repeated CT evaluation and other imaging modalities, for example, (18)F-FDG, were used as the reference standard. RESULTS: According to the reference standard, (68)Ga-DOTA-TOC PET and CT showed a concordant result in 32 patients (70%). In the remaining 14 patients (30%), discrepancies were observed, with a final outcome of progressive disease in 9 patients and remission in 5 patients. (68)Ga-DOTA-TOC PET was correct in 10 patients (21.7%), including 5 patients with progressive disease. In these patients, metastatic spread was detected with the follow-up whole-body PET but was missed when concomitant CT was used. On the other hand, CT confirmed small pulmonary metastases not detected on (68)Ga-DOTA-TOC in 1 patient and progressive liver disease not detected on (68)Ga-DOTA-TOC in 3 patients. Quantitative SUV analysis of individual tumor lesions showed a large range of variability. CONCLUSION: (68)Ga-DOTA-TOC PET shows no advantage over conventional anatomic imaging for assessing response to therapy when all CT information obtained during follow-up is compared. Only the development of new metastases during therapy was detected earlier in some cases when whole-body PET was used. SUV analysis of individual lesions is of no additional value in predicting individual responses to therapy.

Bone metastases in patients with neuroendocrine tumor: 68Ga-DOTA-Tyr3-octreotide PET in comparison to CT and bone scintigraphy.

UNLABELLED: Somatostatin receptor scintigraphy is an accurate imaging modality for the diagnosis of neuroendocrine tumor. Because detection of distant metastases has a major impact on treatment, early diagnosis of metastatic spread is of great importance. So far, no standard procedure has become established for the early diagnosis of bone metastases from neuroendocrine tumor. We compared the diagnostic value of CT with that of the novel somatostatin analog (68)Ga-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ((68)Ga-DOTATOC) in the detection of such metastases. METHODS: Fifty-one patients (22 women and 29 men; age range, 32-87 y) with histologically verified neuroendocrine tumor were included in this study. PET scans were fused with CT scans using a vacuum fixation device. (18)F-NaF or (99m)Tc-dicarboxypropane diphosphonate bone scans or clinical follow-up served as the reference standard. RESULTS: Twelve of the 51 patients had no evidence of bone metastases on any of the available imaging modalities, and 37 patients had (68)Ga-DOTATOC PET results true-positive for bone metastases. (68)Ga-DOTATOC PET results were true-negative for 12 patients, false-positive for one, and false-negative for another, resulting in a sensitivity of 97% and a specificity of 92%. (68)Ga-DOTATOC PET detected bone metastases at a significantly higher rate than did CT (P < 0.001). Furthermore, conventional bone scans confirmed the results of somatostatin receptor PET but did not reveal additional tumors in any patients. CONCLUSION: (68)Ga-DOTATOC PET is a reliable, novel method for the early detection of bone metastases in patients with neuroendocrine tumor. Our results show that CT and conventional bone scintigraphy are less accurate than (68)Ga-DOTATOC PET in the primary staging or restaging of neuroendocrine tumor.

Multimodal evaluation of renal perfusional changes due to extracorporeal shock wave lithotripsy.

OBJECTIVES: To examine the effect of extracorporeal shock wave lithotripsy (ESWL) on renal perfusion before and after treatment, by assessing renal resistive index (RI) using colour Doppler ultrasonography (CDUS), magnetic resonance perfusion imaging (MRPI), radionuclide renography and big-endothelin-1 values (Big-ET-1). PATIENTS AND METHODS: In 69 normotensive patients the RI was measured before, 1, 3, 6 and 24 h after ESWL using CDUS. The RI values, measured in interlobar/arcuate arteries, were correlated with the findings on MRPI, done before and within 24 h after ESWL. In addition, renal plasma flow (RPF, assessed on radionuclide renography) and Big-ET-1 levels (a potent vasoconstrictor peptide), served as a control for evaluating renal perfusion. The patients were stratified in three age groups, i.e. or=60 years, with 23 patients in each group. RESULTS: The mean (sd) RI increased significantly in the treated kidneys, from 0.64 (0.05) before to 0.72 (0.08) after ESWL (P = 0.001). Only in patients aged >or=60 years did the RI continue to increase over the 24 h. MRPI showed a decrease of renal blood flow (RBF) in all age groups, but most significantly in those aged >or=60 years. The radionuclide renography and big-ET-1 levels changed significantly only in the oldest group. The best correlation was between RI and RBF changes detected by MRPI. CONCLUSIONS: ESWL obviously causes disturbances of renal perfusion, particularly in elderly patients (>or=60 years). Measurement of RI with Doppler techniques might provide useful information for the clinical diagnosis of renal damage.

68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT.

UNLABELLED: The aim of this study was to evaluate the diagnostic value of a new somatostatin analog, (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ((68)Ga-DOTA-TOC), for PET in patients with known or suspected neuroendocrine tumors. PET was compared with conventional scintigraphy and dedicated CT. METHODS: Eighty-four patients (48 men, 36 women; age range, 28-79 y; mean age +/- SD, 58.2 +/- 12.2 y) were prospectively studied. For analysis, patients were divided into 3 groups: detection of unknown primary tumor in the presence of clinical or biochemical suspicion of neuroendocrine malignancy (n = 13 patients), initial tumor staging (n = 36 patients), and follow-up after therapy (n = 35 patients). Each patient received 100-150 MBq (68)Ga-DOTA-TOC. Imaging results of PET were compared with (99m)Tc-labeled hydrazinonicotinyl-Tyr(3)-octreotide ((99m)Tc-HYNIC-TOC) and (111)In-DOTA-TOC. CT was also performed on every patient using a multidetector scanner. Each imaging modality was interpreted separately by observers who were unaware of imaging findings before comparison with PET. The gold standard for defining true-positive (TP), true-negative (TN), false-positive (FP), and false-negative (FN) results was based on all available histologic, imaging, and follow-up findings. RESULTS: PET was TP in 69 patients, TN in 12 patients, FP in 1 patient, and FN in 2 patients, indicating a sensitivity of 97%, a specificity of 92%, and an accuracy of 96%. The FP finding was caused by enhanced tracer accumulation in the pancreatic head, and the FN results were obtained in patients with a tumor of the gastrointestinal tract displaying liver metastases. (68)Ga-DOTA-TOC showed higher diagnostic efficacy compared with SPECT (TP in 37 patients, TN in 12 patients, FP in 1 patient, and FN in 34 patients) and diagnostic CT (TP in 41 patients, TN in 12 patients, FP in 5 patients, and FN in 26 patients). This difference was of statistical significance (P < 0.001). However, the combined use of PET and CT showed the highest overall accuracy. CONCLUSION: (68)Ga-DOTA-TOC PET shows a significantly higher detection rate compared with conventional somatostatin receptor scintigraphy and diagnostic CT with clinical impact in a considerable number of patients.

Detection of Sarcomatoid Lung Metastasis With 68GA-PSMA PET/CT in a Patient With Prostate Cancer.

A 70-year-old man with prostate cancer (adenocarcinoma; pT3aN0Mx; GS: 4 + 4) underwent radical prostatectomy and lymph node dissection in February 2008. In December 2009, biochemical recurrence occurred and prostate-specific antigen progressively increased to 4.63 ng/mL despite local salvage radiotherapy and androgen deprivation. Ga-PSMA PET/CT showed a positive left iliac lymph node and a pathological left pulmonary lesion, which was highly positive in a subsequent F-FDG PET/CT. Lymph node resection confirmed an adenocarcinoma metastasis of the prostate cancer and lung surgery demonstrated a sarcomatoid metastasis of prostate cancer. After surgery, prostate-specific antigen decreased to 0.03 ng/mL.

Multicenter Phase II Study Evaluating Two Cycles of Docetaxel, Cisplatin and Cetuximab as Induction Regimen Prior to Surgery in Chemotherapy-Naive Patients with NSCLC Stage IB-IIIA (INN06-Study).

BACKGROUND: Different strategies for neoadjuvant chemotherapy in patients with early stage NSCLC have already been evaluated. The aim of this study was to evaluate the tolerability and efficacy of a chemoimmunotherapy when limited to two cycles. METHODS: Between 01/2007 and 03/2010 41 patients with primarily resectable NSCLC stage IB to IIIA were included. Treatment consisted of two cycles cisplatin (40 mg/m2 d1+2) and docetaxel (75 mg/m2 d1) q3 weeks, accompanied by the administration of cetuximab (400 mg/m2 d1, then 250 mg weekly). The primary endpoint was radiological response according to RECIST. RESULTS: 40 patients were evaluable for toxicity, 39 for response. The main grade 3/4 toxicities were: neutropenia 25%, leucopenia 11%, febrile neutropenia 6%, nausea 8% and rash 8%. 20 patients achieved a partial response, 17 a stable disease, 2 were not evaluable. 37 patients (95%) underwent surgery and in three of them a complete pathological response was achieved. At a median follow-up of 44.2 months, 41% of the patients had died, median progression-free survival was 22.5 months. CONCLUSIONS: Two cycles of cisplatin/ docetaxel/ cetuximab showed promising efficacy in the neoadjuvant treatment of early-stage NSCLC and rapid operation was possible in 95% of patients. Toxicities were manageable and as expected. TRIAL REGISTRATION: EU Clinical Trials Register; Eudract-Nr: 2006-004639-31.

An individual dosimetric approach to 153Sm-EDTMP therapy for pain palliation in bone metastases in correlation with clinical results.

BACKGROUND: The clinical results of therapy using 153Sm ethylenediamine-N,N,N'N'-tetrakis(methylene phosphonic acid) (153Sm-EDTMP) were correlated with radiation dose indices in metastases, with the intention of improving the therapeutic efficacy. METHODS: Fifty-six patients with disseminated bone metastases were treated. Prior to therapy, whole-body scans and single photon emission computed tomography (SPECT) of the trunk were performed. Whole-body retention of 99mTc labelled phosphonates was compared with 153Sm-EDTMP retention after therapy. Estimations of the volumes of bone lesions were done by SPECT. Assuming a solid tumour but a thin metabolically active boundary zone between tumour and healthy bone that absorbed the beta radiation, we estimated an 'irradiated volume' by using a spherical shell model of 6 mm thickness. Local tracer uptake in lesions was assessed by regions of interest techniques on conjugated views of whole-body scans with homogeneous attenuation correction. Calculation of the dose index by applying the Medical Internal Radiation Dosimetry (MIRD) scheme was done retrospectively in 10 patients and prospectively in 22 cases. Depending on changes in pain/mobility scores, results were classified as 'very good', 'good' and 'no response'. RESULTS: A mean dose index > or =10 per lesion was estimated under the condition of a homogeneous uptake within the idealized, spherical, tumour volume. Assuming that the uptake of the radiopharmaceutical occurs mostly within an outer shell of the tumour, dose indices to this 'irradiated volume' can increase to more than twice that value. CONCLUSION: Very good clinical results for bone pain palliation by using 153Sm-EDTMP therapy could be found in patients receiving a dose index >15 per lesion. Even this approximate dosimetric approach, considering the individual differences in tumour spread and the varying intensity of 153Sm uptake, could improve the impact of 153Sm-EDTMP for pain control in cancer patients.

First experience using peptide receptor radionuclide therapy in a patient with urothelial carcinoma.

A 78-year-old man with urothelial carcinoma metastasis after surgical resection of the right kidney, part of the ureter, and urinary bladder in May 2003 and 3 cycles of chemotherapy with cisplatin-gemcitabine was referred for peptide receptor radionuclide therapy (PRRT). Somatostatin-receptor profile was assessed by 68Ga-labeled lanreotide PET, and PRRT was performed using 3738 MBq (101 mCi) of 90Y-DOTA-lanreotide. Because of adequate PRRT response confirmed with MRI and 18F-FDG PET, surgical resection of the solitary cervical metastasis was feasible. Treatment was well tolerated, and the patient remains in complete remission from his urothelial carcinoma.

First experience with proteasome inhibitor treatment of radioiodine nonavid thyroid cancer using bortezomib.

PURPOSE: Radioiodine nonavid thyroid cancer (TC) is a rare disease entity with a poor prognosis. Despite a multimodal therapeutic approach including surgery, chemotherapy, and external beam radiation, radioiodine nonavid TC accounts for a high number of TC-associated deaths. The aim of this investigation was to evaluate the response rate of progressive TC patients to treatment with the proteasome inhibitor bortezomib. MATERIALS AND METHODS: Seven patients with inoperable, metastasized progressive TC proven to be radioiodine nonavid were included into this pilot study. Patients received bortezomib intravenously with a standardized dose of 1.3 mg/m on days 1, 4, 8, and 11. All patients underwent 3 therapeutic cycles with an interval of 10 days. [F]2-deoxy-2-fluoro-D-glucose positron emission tomography (F-FDG PET) and measurements of thyroglobulin levels were performed before, during, and after therapy, with a 6-week interval to post-therapeutic follow-up. RESULTS: Stable disease was seen after proteasome inhibitor therapy in 4 of the 7 patients. Two of the 7 patients showed decrease of maximum standardized uptake value in both post-therapeutic follow-up investigations, and one of these cases also had decreasing thyroglobulin levels. Two patients experienced stable disease during the posttherapeutic follow-up. Two patients showing a mixed response had an improvement in their clinical situation. One patient had rapidly progressive disease, and died 3 months after the last therapeutic cycle. Adverse events included mild polyneuropathy in 2 patients and alterations of the blood count up to WHO (World Health Organization) grade 2 in 5 patients. CONCLUSION: Proteasome inhibitor treatment with bortezomib is a promising therapeutic approach in TC patients without an established treatment alternative. The development of a specific therapeutic regimen for the treatment of radioiodine nonavid TC is warranted.