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Resumen Introduccion La nefrotoxicidad y la hematotoxicidad despues de la terapia con peptidos marcados con radionuclidos (PRRT) se han descrito en multiples estudios usando diferentes actividades acumulativas, numero de ciclos o peptidos marcados con radionuclidos. Aunque los tumores neuroendocrinos (NET) altamente diferenciados con metastasis tienen una larga supervivencia libre de progresion, pueden progresar. Analizamos los efectos secundarios a largo plazo en un esquema de tratamiento homogeneo en pacientes con PRRT y su impacto en el futuro tratamiento oncologico en caso de progresion. Metodos De nuestra base de datos se analizaron 89 de 384 pacientes que recibieron la misma PRRT (Lu-177-DOTATATE o Y-90-DOTATOC) cuatro veces cada 10 a 12 semanas y un seguimiento a los 12 meses. Un paciente recibio tres y 11 pacientes recibieron dos veces cuatro ciclos de PRRT, lo que dio lugar a 102 casos. Se compararon el indice de filtrado glomerular estimado (FGe), la Hb, los globulos blancos y las plaquetas antes del primer ciclo de terapia y un ano despues del cuarto ciclo. La clasificacion del FGe se realizo segun la clasificacion de la enfermedad renal cronica (ERC) y la clasificacion de la hematotoxicidad segun los Criterios Terminologicos Comunes para Eventos Adversos (CTCAE). Tambien se evaluo el impacto de la edad, el sexo, la actividad acumulada y el tipo de PRRT en la toxicidad a largo plazo. Resultados El grado 1-2 del FGe se redujo de 87/102 al inicio a 71 casos en el seguimiento (p Conclusion En aproximadamente 20% de los casos se observa un aumento de la gradacion de la nefrotoxicidad o hematotoxicidad. En estos pacientes, excepto en uno, los niveles de toxicidad fueron leves o moderados un ano despues de completar cuatro ciclos de PRRT con analogos de Y-90 o Lu-177-SST. En terminos de seguridad, la PRRT no tiene un impacto critico en las opciones de tratamiento oncologico posterior en caso de progresion de la enfermedad.

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.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.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.

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.

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. 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). 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). 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.

Coronavirus disease 2019 (COVID-19)-related pneumonia challenges clinical practice. We explore the potential diagnostic benefit of positron emission tomography/computed tomography (PET/CT) in order to establish the underlying inflammatory or fibrotic repair processes in prolonged structural lung abnormalities in COVID-19 patients.Methods: Six post-COVID-19 patients suspected for pulmonary fibrosis were scheduled for dual tracer PET/CT with 18 F-FDG (fluorodeoxyglucose) and 68Ga-fibroblast activation protein inhibitor (FAPI)-46. The uptake of 68 Ga FAPI-46 in the involved lung was compared to a control group of nine non COVID-19 patients. Clinical data and PET/CT imaging were collected and analysed.Results: PET/CT revealed in all six 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. Conclusion: Indicating fibrotic repair mechanisms, 68 Ga-FAPI PET/CT may enhance non-invasive clinical diagnostic performance, drive therapeutic interventions, and facilitate therapeutic response monitoring in patients with long-term CT-abnormalities after severe COVID-19.

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.From our database 89/384 patients receiving the same PRRT (Lu-177-DOTATATE or Y-90-DOTATOC) 4 times every 10 to 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 Common Terminology Criteria for Adverse Events (CTCAE). Impact of age, gender, cumulative activity, type of PRRT on long-term-toxicity was also assessed.eGFR grade 1-2 dropped from 87/102 at the baseline to 71 cases at follow-up (p0.001). 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 (p0.001), 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). CONCLUSIóN: 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.

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 (68)Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC ((68)Ga-PSMA-11) PET/CT. Second, we determined whether intravenous administration of furosemide shortly after tracer injection increases renal washout of (68)Ga-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 (68)Ga-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 (SUV(max)) of organs with physiologic uptake of (68)Ga-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 (68)Ga-PSMA-11 PET/CT. As intensity of (68)Ga-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 (68)Ga-PSMA-11 seems unlikely.

Peptide receptor radionuclide therapy (PRRT) has been used for more than 20 y as a systemic treatment approach in inoperable or metastatic somatostatin receptor-positive tumors. The purpose of this study was to analyze the long-term outcome of PRRT with regard to the most commonly used radiopharmaceuticals, 90Y-DOTATOC and 177Lu-DOTATATE. Methods: This retrospective clinical study included a total of 44 consecutive patients (27 men) with advanced tumors and enhanced somatostatin receptor expression. Mean age at initial diagnosis was 60 y (SD, 11.3 y; range, 40-84 y). Median follow-up was 80 mo. For 177Lu-PRRT, the mean number of cycles administered was 5.3 ± 2.5 and the mean activity was 27.2 ± 14.9 GBq per patient. For 90Y-PRRT, the mean number of cycles administered was 5.5 ± 2.6 and the mean activity was 14.7 ± 7.3 GBq per patient. Overall, 378 cycles were administered (mean, 8.6 ± 3.4 cycles per patient), with an overall cumulative activity of 1,514.1 GBq. Results: Median overall survival was 79 mo. Twenty-one (77.8%) of the 27 men and 9 (52.9%) of the 17 women had died 12 y after commencement of PRRT. The shortest duration of illness was 8 mo and the longest 155 mo. Severe side effects (World Health Organization grades III and IV) were seen in 9 of the 14 patients still alive. Chronic kidney disease in combination with anemia was the most common finding in the 9 patients with severe side effects. A poor prognosis was found for those patients who showed progressive disease, in comparison with patients with cumulative disease control after initial PRRT (log rank, P < 0.001), whereas women and patients with no more than 2 tumor sites seemed to especially benefit from PRRT (not reaching significance levels). Conclusion: PRRT is encouraging in terms of long-term outcome. Thirty-two percent (14/44 patients) of the patients with metastatic or inoperable disease were still alive more than 12 y after the beginning of radionuclide therapy. Possible predictors for favorable outcome are having an initial response to PRRT, having a low number of affected sites, and being female.

In patients with metastatic gastroenteropancreatic neuroendocrine tumors (NETs), we evaluated health-related quality of life (HRQoL) from the first peptide receptor radionuclide therapy (PRRT) to the first restaging and compared the scores with general-population (GP) norms. Methods: The data were from routine HRQoL monitoring using the core quality-of-life questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30). Patients received 4-6 cycles of 177Lu-DOTATATE or 90Y-DOTATOC. To be eligible for analysis, patients had to have at least one HRQoL assessment before PRRT and at least one HRQoL assessment at the end of or after treatment completion. Linear mixed models were used to consider HRQoL changes over time. Results: In total, 61 gastroenteropancreatic NET patients (small-intestine NETs, n = 37; pancreatic NETs, n = 24) were eligible for analysis. Clear improvements from baseline to the first restaging were found for diarrhea in small-intestine NET patients, showing a decrease of 16 points, which represents a moderately large change. We observed a clinically relevant decrease in appetite loss (17 points), but for female small-intestine NET patients only. Other HRQoL changes were also restricted to sociodemographic or clinical subgroups and mainly reflected improvements, except for physical and social functioning, which showed decreasing scores in older small-intestine NET patients. Compared with HRQoL GP norms, patients had impairments consisting of diarrhea; fatigue; appetite loss; reduced physical, social, and role functioning; and reduced global HRQoL. Except for diarrhea and appetite loss, patient scores at the first restaging did not reach GP levels. Conclusion: Our analyses support previous findings of overall stable HRQoL under PRRT. Yet, significant HRQoL impairments compared with the GP and potentially specific subgroup patterns need to be considered.

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. 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. 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

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 [Comparison of four groups with 50 patients each, receiving different preparation prior to [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 SUVPerforming [

As radionuclide therapy is gaining importance in palliative treatment of patients suffering from neuroendocrine tumour (NET) as well as castration resistant prostate cancer (CRPC), the radiation protection of patients, staff, family members and the general public is of increasing interest. Here, we determine patient discharge dates according to European guidelines.In 40 patients with NET and 25 patients with CRPC organ and tumour doses based on the MIRD concept were calculated from data obtained during the first therapy cycle. Planar whole body images were recorded at 0.5, 4, 20, 68 und 92 h postinjection. Residence times were calculated from the respective time-activity-curves based on the conjugated view method. Residence times for critical organs were fitted into the commercially available OLINDA software to calculate the organ doses. The doses of tumours and salivary glands were calculated via their self-irradiation by approximation with spheres of equivalent volume. Kidney volumes were gained by organ segmentation, volumes of all other organs were estimated by means of OLINDA and hence were lean body mass corrected. Out of the whole body curves reference points for patient discharge were estimated.In patients with NET discharge dates could be properly estimated from dosimetric data, which is not only crucial for radiation protection, but also makes therapy planning easier. ForPatient release is predictable for

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).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).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.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.

The purpose of this study was to investigate the diagnostic performance ofSixteen metastatic PC patients with known skeletal metastases, who underwent bothIn contrast to 468 PET-positive lesions suggestive of bone metastases onIn comparison to

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.. 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. 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

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.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.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.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.

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

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.

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

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.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.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%.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.

We wanted to establish the range of (68)Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT).In 249 patients, 390 (68)Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies).SUVmax (mean ± standard deviation) values of (68)Ga-DOTA-TOC were 29.8 ± 16.5 in 162 liver metastases, 19.8 ± 18.8 in 89 bone metastases and 34.6 ± 17.1 in 43 pancreatic NET (33.6 ± 14.3 in 30 tumours of the uncinate process and 36.3 ± 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUVmax (p 0.02) was found in liver metastases of NET patients treated with PRRT. There were significant differences in SUVmax between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process (p 0.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUVmax for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively (p 0.0001).(68)Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUVmax can offer important clinical information to distinguish between physiological and pathological somatostatin receptor expression, especially in the uncinate process. PRRT does not significantly influence SUVmax, except in liver metastases of patients with NET.

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 β-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.