Impact of forced diuresis with furosemide and hydration on the halo artefact and intensity of tracer accumulation in the urinary bladder and kidneys on [68Ga]Ga-PSMA-11-PET/CT in the evaluation of prostate cancer patients.

PURPOSE: to assess the influence of intravenous hydration and forced diuresis with furosemide in two different dosages (20 vs 40 mg) on the intensity of tracer accumulation in the urinary collection system and on the occurrence of halo artefact surrounding the urinary bladder and kidneys in [68Ga]Ga-PSMA-11-PET/CT scans. MATERIALS AND METHODS: Comparison of four groups with 50 patients each, receiving different preparation prior to [68Ga]Ga-PSMA-11-PET/CT. Group one, no preparation. Group two, 500 ml sodium chloride administered immediately after tracer injection. Group three, 500 ml sodium chloride and injection of 20 mg furosemide immediately after tracer administration. Group four, 500 ml sodium chloride and injection of 40 mg furosemide immediately after tracer injection. Images were judged visually whether halo artefact was present; semiquantitative measurements were performed with standardised uptake value (SUV). RESULTS: Halo artefact of the urinary bladder was present in twelve patients without preparation, in eight patients receiving only sodium chloride, in one patient injected with 20 mg furosemide/sodium chloride and in two patients receiving 40 mg furosemide/sodium chloride, showing a median SUVmean in the bladder of 45.8, 14.4, 4.6 and 5.8, respectively. Differences between patient group without preparation and the two groups with furosemide/sodium chloride were statistically significant. Patient groups receiving 20 mg furosemide and 40 mg furosemide did not differ significantly. Renal halo artefacts were observed in 15 patients of group one, in ten patients of group two, in 14 patients of group three and in 14 patients of group four, with corresponding median SUVmean values of 33.9, 32.0, 37.8 and 30.4 (no statistically significant differences). CONCLUSION: Performing [68Ga]Ga-PSMA-11-PET/CT, intravenous injection of 20-mg furosemide and 500-ml sodium chloride significantly reduces the number of bladder halo artefacts and intensity of tracer accumulation in the urinary bladder. A total of 40 mg furosemide does not further improve results.

The 68Ga/177Lu-theragnostic concept in PSMA-targeting of metastatic castration-resistant prostate cancer: impact of post-therapeutic whole-body scintigraphy in the follow-up.

INTRODUCTION: A new therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) of heavily pre-treated patients lies in 177Lu-PSMA-617 radioligand therapy. METHODS: On the basis of PSMA-targeted 68Ga-PSMA-11 PET/CT, 32 consecutive mCRPC patients were selected for 177Lu-PSMA-617 therapy (6 GBq/cycle, 2 to 6 cycles, 6-10 weeks apart) and followed until death. Post-therapy whole-body (WB) dosimetry and 68Ga-PSMA-11 PET/CT data were compared and related to progression free and overall survival. RESULTS: 177Lu-PSMA-617 dosimetry after the first cycle indicated high tumor doses for skeletal (4.01 ± 2.64; range 1.10-13.00 Gy/GBq), lymph node (3.12 ± 2.07; range 0.70-8.70 Gy/GBq), and liver (2.97 ± 1.38; range 0.76-5.00 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 24 GBq. Any PSA decrease after the first cycle was found in 23/32 (72%), after the second cycle in 22/32 (69%), after the third cycle in 16/28 (57%), and after the fourth cycle in 8/18 (44%) patients. Post-therapy 24 h WB scintigraphy showed decreased tumor-to-background ratios in 24/32 (75%) after the first therapy cycle, after the second cycle in 17/29 (59%), and after the third cycle in 13/21 (62%) patients. The median PFS was 7 months and the median OS 12 months. In the group of PSA responders (n = 22) the median OS was 17 months versus 11 months in the group of non-responders (n = 10), p < 0.05. Decreasing SUVmax values were found for parotid (15.93 ± 6.23 versus 12.33 ± 4.07) and submandibular glands (17.65 ± 7.34 versus 13.12 ± 4.62) following treatment, along with transient (n = 6) or permanent (n = 2) xerostomia in 8/32 (25%) patients. In 3/32 patients, nephrotoxicity changed from Grade 2 to 3, whereas neither Grade 4 nephrotoxicity nor hematotoxicity was found. In most patients a good agreement was observed for the visual interpretation of the tracer accumulation between 24 h WB and PET/CT scans. However, no significance could be calculated for baseline-absorbed tumor doses and SUVmax values of tumor lesions. 5/32 (16%) patients showed a mixed response pattern, which resulted in disease progression over time. CONCLUSION: Serial PSA measurements and post-therapy 24 h WB scintigraphy seems to allow a sufficiently accurate follow-up of 177Lu-PSMA-617-treated mCRPC patients whereas 68Ga-PSMA-11 PET/CT should be performed for patient selection and final response assessment.

Correction to: The 68Ga/177Lu-theragnostic concept in PSMA-targeting of metastatic castration-resistant prostate cancer: impact of post-therapeutic whole-body scintigraphy in the follow-up.

The author name Bernhard Nilica was inadvertently interchanged in the original version of this article.

Comparison of [68Ga]Ga-PSMA-11 PET/CT with [18F]NaF PET/CT in the evaluation of bone metastases in metastatic prostate cancer patients prior to radionuclide therapy.

AIM: The purpose of this study was to investigate the diagnostic performance of 68Ga-PSMA-11 PET/CT in the evaluation of bone metastases in metastatic prostate cancer (PC) patients scheduled for radionuclide therapy in comparison to [18F]sodium fluoride (18F-NaF) PET/CT. METHODS: Sixteen metastatic PC patients with known skeletal metastases, who underwent both 68Ga-PSMA-11 PET/CT and 18F-NaF PET/CT for assessment of metastatic burden prior to radionuclide therapy, were analysed retrospectively. The performance of both tracers was calculated on a lesion-based comparison. Intensity of tracer accumulation of pathologic bone lesions on 18F-NaF PET and 68Ga-PSMA-11 PET was measured with maximum standardized uptake values (SUVmax) and compared to background activity of normal bone. In addition, SUVmax values of PET-positive bone lesions were analysed with respect to morphologic characteristics on CT. Bone metastases were either confirmed by CT or follow-up PET scan. RESULTS: In contrast to 468 PET-positive lesions suggestive of bone metastases on 18F-NaF PET, only 351 of the lesions were also judged positive on 68Ga-PSMA-11 PET (75.0%). Intensity of tracer accumulation of pathologic skeletal lesions was significantly higher on 18F-NaF PET compared to 68Ga-PSMA-11 PET, showing a median SUVmax of 27.0 and 6.0, respectively (p < 0.001). Background activity of normal bone was lower on 68Ga-PSMA-11 PET, with a median SUVmax of 1.0 in comparison to 2.7 on 18F-NaF PET; however, tumour to background ratio was significantly higher on 18F-NaF PET (9.8 versus 5.9 on 68Ga-PSMA-11 PET; p = 0.042). Based on morphologic lesion characterisation on CT, 18F-NaF PET revealed median SUVmax values of 23.6 for osteosclerotic, 35.0 for osteolytic, and 19.0 for lesions not visible on CT, whereas on 68Ga-PSMA-11 PET median SUVmax values of 5.0 in osteosclerotic, 29.5 in osteolytic, and 7.5 in lesions not seen on CT were measured. Intensity of tracer accumulation between18F-NaF PET and 68Ga-PSMA-11 PET was significantly higher in osteosclerotic (p < 0.001) and lesions not visible on CT (p = 0.012). CONCLUSION: In comparison to 68Ga-PSMA-11 PET/CT, 18F-NaF PET/CT detects a higher number of pathologic bone lesions in advanced stage PC patients scheduled for radionuclide therapy. Our data suggest that 68Ga-PSMA-11 PET should be combined with 18F-NaF PET in PC patients with skeletal metastases for restaging prior to initiation or modification of therapy.

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.

Current knowledge on the sensitivity of the (68)Ga-somatostatin receptor positron emission tomography and the SUVmax reference range for management of pancreatic neuroendocrine tumours.

Physiologically increased pancreatic uptake at the head/uncinate process is observed in more than one-third of patients after injection of one of the three (68)Ga-labelled octreotide-based peptides used for somatostatin (sst) receptor (r) imaging. There are minor differences between these (68)Ga-sstr-binding peptides in the imaging setting. On (68)Ga-sstr-imaging the physiological uptake can be diffuse or focal and usually remains stable over time. Differences in the maximal standardised uptake values (SUVmax) reported for the normal pancreas as well as for pancreatic neuroendocrine tumour (PNET) lesions may be related to several factors, including (a) differences in the peptide binding affinities as well as differences in sstr subtype expression of pancreatic α- and ß-cells, and heterogeneity / density of tumour cells, (b) differences in scanner resolution, image reconstruction techniques and acquisition protocols, (c) mostly retrospective study designs, (d) mixed patient populations, or (e) interference with medications such as treatment with long-acting sst analogues. The major limitation in most of the studies lies in the lack of histopathological confirmation of abnormal findings. There is a significant overlap between the calculated SUVmax-values for physiological pancreas and PNET-lesions of the head/uncinate process that do not favour the use of quantitative parameters in the clinical setting. Anecdotal long-term follow-up studies have even indicated that increased uptake in the head/uncinate process still can turn out to be malignant over years of follow up. SUVmax-data for the pancreatic body and tail are limited. Therefore, any visible focal tracer uptake in the pancreas must be considered as suspicious for malignancy irrespective of quantitative parameters. In general, sstr-PET/CT has significant implications for the management of NET patients leading to a change in treatment decision in about one-third of patients. Therefore, follow-up with (68)Ga-sstr-PET/CT is mandatory in the clinical setting if uptake in the head/uncinate process is observed.

Systematic review reveals lack of quality in reporting health-related quality of life in patients with gastroenteropancreatic neuroendocrine tumours.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumours (GEP-NET) are often slow-growing and patients may live for years with metastasised disease. Hence, along with increasing overall and progression-free survival, treatments aim at preserving patients' well-being and health-related quality of life (HRQoL). However, studies on systematic HRQoL assessment in patients with GEP-NET are scarce. Therefore, the purpose of the current review is to systematically evaluate the methodological quality of the identified studies. METHODS: A targeted database search was performed in PubMed, EMBASE, and CENTRAL. Data extraction was conducted by two independent researchers according to predefined criteria. For study evaluation, the Minimum Standard Checklist for Evaluating HRQoL Outcomes in Cancer Clinical Trials and the CONSORT Patient-Reported Outcome extension were adapted. RESULTS: The database search yielded 48 eligible studies. We found the awareness for the need of HRQoL measurement to be growing and application of cancer-specific instruments gaining acceptance. Overall, studies were too heterogeneous in terms of patient characteristics and treatment interventions to draw clear conclusions for clinical practice. More importantly, a range of methodological shortcomings has been identified which were mainly related to the assessment and statistical analysis, as well as the reporting and interpretation of HRQoL data. CONCLUSION: Despite an increasing interest in HRQoL in GEP-NET patients, there is still a lack of knowledge on this issue. A transfer of HRQoL results into clinical practice is hindered not only by the scarceness of studies, but also by the often limited quality of HRQoL processing and reporting.

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.

Persistent quality of life impairments in differentiated thyroid cancer patients: results from a monitoring programme.

PURPOSE: Health-related quality of life (HRQOL) in differentiated thyroid cancer (DTC) research has so far received little attention and available results are conflicting. We studied the HRQOL of radioiodine-naive DTC patients in comparison with the general population (GP), investigated the course of HRQOL up to 30 months after radioiodine remnant ablation (RAA) and sought to identify patient characteristics associated with HRQOL. METHODS: We analysed data from routine HRQOL monitoring at a nuclear medicine department. Between 2005 and 2013, a total of 439 thyroid cancer patients (all histologies) completed the EORTC Quality of Life Questionnaire Core-30 (QLQ-C30) at least once during their treatment at the department. We compared patients' baseline HRQOL scores before RAA with scores from age-matched and sex-matched controls from the Austrian GP. We then determined the course of HRQOL over the 30 months after RAA and assessed the impact of the following clinical variables on HRQOL: method of thyroid-stimulating hormone (TSH) stimulation, histology (papillary vs. follicular) and disease stage. RESULTS: A total of 284 patients (mean age 48.3 years, SD 15.0 years; 71.6% women; 80.7% papillary type) with a baseline HRQOL assessment before RAA were available. We found clinically meaningful differences in the detriment in patients on almost all domains. These were largest for fatigue (23 points) and role functioning (25 points). Data from 241 patients (mean age 48.6 years, SD 15.9 years; 68.9% women; 76.3% papillary type) were included in the longitudinal analysis. Investigating the course of HRQOL, a significant improvement over time was found for role and emotional functioning, fatigue, pain, and dyspnoea. A range of HRQOL scores were improved in patients with exogenous TSH stimulation, but some scores both in patients with exogenous TSH stimulation and in those followed for 30 months, especially fatigue and role functioning, did not reach levels in the GP sample. CONCLUSION: Our results show that the favourable prognosis of DTC does not directly translate into good HRQOL in these patients. Persistent restrictions in regaining their normal daily life in terms of work and leisure highlight the importance of more detailed investigation of DTC patients' wellbeing, support needs, and disease experience.

(68)Ga-DOTATOC PET/CT provides accurate tumour extent in patients with extraadrenal paraganglioma compared to (123)I-MIBG SPECT/CT.

PURPOSE: The aim of this study was to compare the accuracy of (123)I-MIBG SPECT/CT with that of (68)Ga-DOTATOC PET/CT for staging extraadrenal paragangliomas (PGL) using both functional and anatomical images (i.e. combined cross-sectional imaging) as the reference standards. METHODS: The study included three men and seven women (age range 26 to 73 years) with anatomical and/or histologically proven disease. Three patients had either metastatic head and neck PGL (HNPGL) or multifocal extraadrenal PGL, and seven patients had nonmetastatic extraadrenal disease. Comparative evaluation included morphological imaging with CT, functional imaging with (68)Ga-DOTATOC PET, and (123)I-MIBG imaging. The imaging results were analysed on a per-patient and on a per-lesion basis. RESULTS: On a per-patient basis, the detection rate of (68)Ga-DOTATOC PET was 100 %, whereas that of planar (123)I-MIBG imaging was 10.0 % and with SPECT/CT 20.0 % for both nonmetastatic and metastatic/multifocal extraadrenal PGL. On a per-lesion basis, the overall sensitivity of (68)Ga-DOTATOC PET was 100 % (McNemar p < 0.5), that of planar (123)I-MIBG imaging was 3.4 % (McNemar p < 0.001) and that of SPECT/CT was 6.9 % (McNemar p < 0.001). Both (68)Ga-DOTATOC PET and anatomical imaging identified 27 lesions. Planar (123)I-MIBG imaging identified only one lesion, and SPECT/CT two lesions. Two additional lesions were detected by (68)Ga-DOTATOC PET but not by either (123)I-MIBG or CT imaging. CONCLUSION: Our analysis in this patient cohort indicated that (68)Ga-DOTATOC PET/CT is superior to (123)I-MIBG SPECT/CT, particularly in head and neck and bone lesions, and provides valuable information for staging extraadrenal PGL, particularly in patients with surgically inoperable tumours or multifocal/malignant disease.

(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.

Peptide Receptor Radionuclide Therapy in Merkel Cell Carcinoma: A Comprehensive Review.

Merkel cell carcinoma is a rare, aggressive skin malignancy, also known as neuroendocrine carcinoma of the skin, with high rates of recurrence and distant metastasis. In refractory metastatic Merkel cell carcinoma (mMCC), besides immunotherapy, chemotherapy, and radiation, peptide receptor radionuclide therapy (PRRT) may be a viable option since this type of tumor can express somatostatin receptors. Methods: We performed a comprehensive review of the literature to evaluate the efficacy of PRRT in mMCC patients. Results: Thirty-seven patients with mMCC received PRRT (1-5 cycles) with 177Lu- or 90Y-labeled somatostatin analogs (cumulative activity, 1.5-30 GBq). Radiographic response was available for 19 of 28 patients who received PRRT alone. Six (31.6%) of 19 patients showed objective responses, from partial to complete, and no severe adverse events were reported. Conclusion: Our analysis supports the use of PRRT in mMCC with sufficient somatostatin receptor uptake, although the quality of the available evidence is low. Prospective clinical trials are already in development and have started accruing in some parts of the world.

Nephrotoxicity and hematotoxicity one year after four cycles of peptide receptor radionuclide therapy (PRRT) and its impact on future treatment planning - A retrospective analysis.

PURPOSE: Nephro- and hematotoxicity after peptide receptor radionuclide therapy (PRRT) have been described in multiple studies with heterogeneous cumulative activities, number of cycles or radiolabelled peptides. Though highly differentiated metastasized neuroendocrine tumours (NET) have long progression free survival, they may progress. We analysed long-term side effects in a homogenous treatment schedule in PRRT-patients and their impact on future oncologic treatment in case of progression. METHODS: From our database 89/384 patients receiving the same PRRT (Lu-177-DOTATATE or Y-90-DOTATOC) 4 times every 10-12 weeks and a follow-up at 12 months were analysed. One patient had three and 11 patients had two times four PRRT-cycles resulting in 102 cases. eGFR, Hb, WBC and platelets before the first and one year after the fourth therapy cycle were compared. eGFR-Grading was done according to chronic kidney disease classification (CKD) and grading of hematotoxicity according to CTCAE. Impact of age, gender, cumulative activity, type of PRRT on long-term-toxicity was also assessed. RESULTS: eGFR grade 1-2 dropped from 87/102 at the baseline to 71 cases at follow-up (p < 0.001). Before treatment grade 3a was found in 13, grade 3b in 2 cases, and at follow-up grade 3a in 25, grade 3b in 5, and grade 4 in 1 case. Anaemia prior to PRRT and at follow-up was grade 0 in 63 versus 48 (p < 0.001), grade 1 in 36 versus 48, and grade 2 in three versus six cases. In white blood cell count and platelets, there were no significant changes in grading occurring. Subgroup analysis revealed that only in the age group 65 and older was there a higher incidence for anaemia (p = 0.006). CONCLUSION: In roughly 20% of cases an increase in grading of nephro- or hematotoxicity is observed. In those patients, except in one, toxicity findings were mild or moderate one year after completion of four cycles of PRRT with either Y-90- or Lu-177-SST-analogues. In terms of safety, PRRT has no critical impact on further oncologic treatment options in the case of disease progression.

Enhancing Clinical Diagnosis for Patients With Persistent Pulmonary Abnormalities After COVID-19 Infection: The Potential Benefit of 68 Ga-FAPI PET/CT.

PATIENTS AND METHODS: Six post COVID-19 patients suspected for pulmonary fibrosis were scheduled for dual-tracer PET/CT with 18 F-FDG and 68 Ga-fibroblast activation protein inhibitor (FAPI)-46. The uptake of 68 Ga-FAPI-46 in the involved lung was compared with a control group of 9 non-COVID-19 patients. Clinical data and PET/CT imaging were collected and analyzed. RESULTS: PET/CT revealed in all 6 pulmonary impaired patients the reduced glucose avidity on 18 F-FDG and clear positivity on 68 Ga-FAPI-46 PET/CT in comparison to the control group. CONCLUSIONS: Enhancing fibrotic repair mechanisms, 68 Ga-FAPI PET/CT may improve noninvasive clinical diagnostic performance in patients with long-term CT abnormalities after severe COVID-19. Although this study shows promising results, additional studies in larger populations are required to establish a general diagnostic guideline.

Long-Term Survival and Value of 18F-FDG PET/CT in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with Second Peptide Receptor Radionuclide Therapy Course with 177Lu-DOTATATE.

Peptide receptor radionuclide therapy (PRRT) has been recognized as a promising therapy against neuroendocrine tumors (NETs). The use of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in NETs has been a matter of controversy. The purpose of this study was to evaluate the long-term survival and efficacy of a second PRRT course with 177Lu-DOTATE in patients with advanced gastroenteropancreatic (GEP) NETs. Furthermore, the value of 18F-FDG PET/CT in these patients was evaluated. 40 patients with GEP NETs who underwent two PRRT courses with 177Lu-DOTATATE and combined examinations with 68Ga-DOTA-TOC and 18F-FDG PET/CT were evaluated. After the second PRRT course, two patients (5.0%) were in partial remission, 21 patients (52.5%) in stable disease and 17 patients (42.5%) had progressive disease. The median overall survival was 122.10 months. After the second PRRT course, the median overall survival was significantly higher (p = 0.033) in the 18F-FDG-negative group compared to the 18F-FDG-positive group (145.50 versus 95.06 months, respectively). The median time to progression was 19.37 months. In conclusion, a second PRRT course with 177Lu-DOTATE is an effective treatment approach for GEP NET patients with disease progression. A change in 18F-FDG status after PRRT may predict the disease course and survival. Patients who are 18F-FDG-negative have a significantly longer overall survival than those who are 18F-FDG-positive.

Comparison of Early Imaging and Imaging 60 min Post-Injection after Forced Diuresis with Furosemide in the Assessment of Local Recurrence in Prostate Cancer Patients with Biochemical Recurrence Referred for 68Ga-PSMA-11 PET/CT.

BACKGROUND: 68Ga-PSMA-11 PET/CT is a promising method for the assessment of local recurrence (LR) in prostate cancer (PCa) patients. The aim of this study was to evaluate the diagnostic performance of early 68Ga-PSMA-11 PET imaging in comparison to 68Ga-PSMA-11 PET imaging 60 min post-injection (p.i.) in the detection of LR in patients with biochemical recurrence (BR) of prostate carcinoma. MATERIALS AND METHODS: 190 image sets of patients with BR in PCa who underwent 68Ga-PSMA-11 PET/CT were assessed retrospectively (median prostate specific antigen (PSA) value, 0.70 ng/mL (range, 0.1-105.6 ng/mL)). Patients received an early static scan of the pelvic area (median, 248 s p.i. (range, 56-923 s)) and a whole-body scan 60 min p.i. (median, 64 min p.i. (range, 45-100 min)) with intravenous administration of 20 mg furosemide i.v. at the time of tracer application, followed by intravenous hydration with 500 mL of sodium chloride (NaCl 0.9%). Assessment was based on visual analysis and calculation of the maximum standardized uptake value (SUVmax) of the pathologic lesions present in the prostate fossa found in the early PET imaging and 60 min PET scans. The scans were characterized as negative, positive, or equivocal. The results were compared, and the combination of early and 60 min p.i. imaging was evaluated. RESULTS: Image assessment resulted in 30 (15.8%) positive, 17 (8.9%) equivocal, and 143 (75.3%) negative findings in early scans, and 28 (14.7%) positive, 25 (13.2%) equivocal, and 137 (72.1%) negative findings of LR in 60 min p.i. images. For combined image analysis, 33 (17.4%) cases were positive and 20 (10.5%) were equivocal. There was no statistical significance between the number of positive (p = 0.815), negative (p = 0.327), and equivocal (p = 0.152) findings. Furthermore, the combination of both scans showed no statistically significant differences for the positive and negative findings (p = 0.063). The median SUVmax was 4.9 (range, 2.0-55.2) for positive lesions in the early scans and 8.0 (range, 2.1-139.9) in the scans 60 min p.i. The median SUVmax for bladder activity was 2.5 (range, 0.9-12.2) in the early scans and 8.2 (range, 1.8-27.6) in the scans 60 min p.i. CONCLUSION: Early static imaging additional to 68Ga-PSMA-11 PET images acquired 60 min p.i. has limited value in patients prepared with furosemide and hydration, and showed no statistically significant change in the detection rate (DR) of LR and the number of equivocal findings. Based on our results, in departments following a protocol with forced diuresis, including furosemide, additional early static imaging cannot be routinely recommended for the assessment of BR in PCa patients.

Early Injection of Furosemide Increases Detection Rate of Local Recurrence in Prostate Cancer Patients with Biochemical Recurrence Referred for 68Ga-PSMA-11 PET/CT.

The aim of this study was twofold. First, we aimed to assess the impact of forced diuresis with early furosemide injection on the detection rate of local recurrence in prostate cancer patients with biochemical recurrence referred for 68Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (68Ga-PSMA-11) PET/CT. Second, we determined whether intravenous administration of furosemide shortly after tracer injection increases renal washout of 68Ga-PSMA-11 before it binds to the PSMA receptor with possible influence on biodistribution and intensity of tracer uptake in organs with physiologic tracer accumulation. Methods: In a retrospective analysis, 2 different groups with 220 prostate cancer patients each, referred for 68Ga-PSMA-11 PET/CT because of biochemical recurrence after primary therapy, were compared: patients in group 1 (median prostate-specific antigen, 1.30 ng/mL) received no preparation before imaging, whereas patients in group 2 (median prostate-specific antigen, 0.82 ng/mL) were injected with 20 mg of furosemide and 500 mL of sodium chloride (NaCl 0.9%) immediately after tracer injection. The presence of local recurrence was assessed visually. In addition, the intensity of tracer accumulation in organs with physiologic tracer uptake was evaluated. Results: The detection rate of lesions judged positive for local recurrence was significantly higher in patients receiving furosemide than in patients without preparation: 56 cases (25.5%) versus 38 cases (17.3%), respectively (P = 0.048). Median maximum SUVs (SUVmax) of organs with physiologic uptake of 68Ga-PSMA-11 in groups 1 and 2 were urinary bladder (63.0 vs. 8.9), kidney (55.6 vs. 54.5), liver (9.9 vs. 9.4), spleen (11.2 vs. 11.9), small bowel (16.2 vs. 17.1), parotid gland (19.2 vs. 19.6), lacrimal gland (8.9 vs. 10.9), blood-pool activity (2.2 vs. 2.3), muscle (1.0 vs. 1.1), and bone (1.6 vs. 1.6). Apart from bladder activity, no significant reduction of tracer accumulation was found in the patient group receiving furosemide. Conclusion: Injection of 20 mg of furosemide at the time point of radiotracer administration significantly increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence referred for 68Ga-PSMA-11 PET/CT. As intensity of 68Ga-PSMA-11 uptake in organs with physiologic uptake is not significantly reduced, a negative impact of early furosemide injection on targeting properties and biodistribution of 68Ga-PSMA-11 seems unlikely.