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,N9,N$,N$9-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 6 SD, 58.2 6 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 5 13 patients), initial tumor staging (n 5 36 patients), and follow-up after therapy (n 5 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.

The GS and PSA level correlated with the intensity of tracer accumulation in the primary tumours of PC patients on Ga-PSMA-11 PET/CT. As PC tumours with GS 6+7 and patients with PSA values ≤10 ng/ml showed significantly lowerGa-PSMA-11 uptake, Ga-PSMA-11 PET/CT should be preferentially applied for primary staging of PC in patients with GS>7 or PSA levels ≥10 ng/ml.

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.

68 Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N9,N99,N999-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.

AimsThere is a controversy as to the relative efficacy of 177Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether 177Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743).MethodsThe review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in Pubmed and Embase selected articles up to September 2017. A search in ClinicalTrials.gov indicated ongoing studies. The meta-analysis used the random-effects model.ResultsTwelve studies including 669 patients reported 177Lu-PSMA RLT. Overall, 43% of the patients had a maximum decline of PSA of ≥50% following treatment with 177Lu-PSMA RLT. The treatment with 177Lu-PSMA-617 and 177Lu-PSMA for imaging and therapy (I&T) had mainly transient adverse effects. Sixteen studies including 1338 patients reported third-line treatment. Overall, 21% of the patients had a best decline of PSA of ≥50% following third-line treatment. After third-line treatment with enzalutamide and cabazitaxel, adverse effects caused discontinuation of treatment for 10% to 23% of the patients. 177Lu-PSMA RLT gave a best PSA decline ≥50% more often than third-line treatment (mean 44% versus 22%, p = 0.0002, t test). 177Lu-PSMA RLT gave objective remission more often than third-line treatment (overall 31 of 109 patients versus 43 of 275 patients, p = 0.004, χ2 test). Median survival was longer after 177Lu-PSMA RLT than after third-line treatment, but the difference was not statistically significant (mean 14 months versus 12 months, p = 0.32, t test). Adverse effects caused discontinuation of treatment more often for third-line treatment than for 177Lu-PSMA RLT (22 of 66 patients versus 0 of 469 patients, p < 0.001, χ2 test).ConclusionsAs for patients with mCRPC, treatment with 177Lu-PSMA-617 RTL and 177Lu-PSMA I&T gave better effects and caused fewer adverse effects than third-line treatment.

The aim of this review is to report on the current status of prostate-specific membrane antigen (PSMA)-directed theranostics in prostate cancer (PC) patients. The value of 68Ga-PSMA-directed PET imaging as a diagnostic procedure for primary and recurrent PC as well as the role of evolving PSMA radioligand therapy (PRLT) in castration-resistant (CR)PC is assessed. The most eminent data from mostly retrospective studies currently available on theranostics of prostate cancer are discussed. The current knowledge on 68Ga-PSMA PET/CT implicates that primary staging with PET/CT is meaningful in patients with high-risk PC and that the combination with pelvic multi parametric (mp)MR (or PET/mpMR) reaches the highest impact on patient management. There may be a place for 68Ga-PSMA PET/CT in intermediate-risk PC patients as well, however, only a few data are available at the moment. In secondary staging for local recurrence, 68Ga-PSMA PET/mpMR is superior to PET/CT, whereas for distant recurrence, PET/CT has equivalent results and is faster and cheaper compared to PET/mpMR. 68Ga-PSMA PET/CT is superior to 18F / 11Choline PET/CT in primary staging as well as in secondary staging. In patients with biochemical relapse, PET/CT positivity is directly associated with prostate-specific antigen (PSA) increase and amounts to roughly 50% when PSA is raised to ≤0.5 ng/ml and to ≥90% above 1 ng/ml. Significant clinical results have so far been achieved with the subsequent use of radiolabeled PSMA ligands in the treatment of CRPC. Accumulated activities of 30 to 50 GBq of 177Lu-PSMA ligands seem to be clinically safe with biochemical response and PERCIST/RECIST response in around 75% of patients along with xerostomia in 5–10% of patients as the only notable side effect. On the basis of the current literature, we conclude that PSMA-directed theranostics do have a major clinical impact in diagnosis and therapy of PC patients. We recommend that 68Ga-PSMA PET/CT should be performed in primary staging together with pelvic mpMR in high-risk patients and in all patients for secondary staging, and that PSMA-directed therapy is a potent strategy in CRPC patients when other treatment options have failed. The combination of PSMA-directed therapy with existing therapy modalities (such as 223Ra-chloride or androgen deprivation therapy) has to be explored, and prospective clinical multicenter trials with theranostics are warranted.

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,N9,N$,N999-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.

We hope that by developing these consensus guidelines on the interpretation of 68Ga-PSMA PET/CT, clinicians reporting these studies will be able to provide more consistent clinical reports and that within clinical trials, abnormality classifications will be harmonized, allowing more robust assessment of its diagnostic performance.