Prediction of clinically significant prostate cancer by [68 Ga]Ga-PSMA-11 PET/CT: a potential tool for selecting patients for active surveillance.

PURPOSE: In our study, our aim was to investigate the role of [68 Ga]Ga-PSMA-11 PET /CT imaging in the diagnosis of clinically significant prostate cancer (csPCa) (ISUP GG 2 and higher) in patients initially diagnosed with ISUP GG 1 and 2 after prostate biopsy. MATERIALS AND METHODS: We retrospectively reviewed 147 patient records in whom [68 Ga]Ga-PSMA-11 PET/CT imaging was performed preoperatively. All patients were initially diagnosed with ISUP GG 1 and 2 PCa by biopsy. Final pathology reports were obtained after radical prostatectomy. The [68 Ga]Ga-PSMA-11 PET/CT images were evaluated to determine the PRIMARY score. Patients' mpMRI-PIRADS scores were also recorded when available and analyzed in correlation with the pathology results. RESULTS: For the 114 patients scored using PRIMARY, 19 out of 37 patients with scores of 1 and 2 (51%) were diagnosed with csPCa. Of the 77 patients with PRIMARY scores between 3 and 5, 64 (83%) had csPCa. Notably, every patient with a PRIMARY score of 5 had csPCa. PRIMARY scoring had a sensitivity of 77% and specificity of 58%, with a positive predictive value of 83%. A moderate correlation was observed between PRIMARY scores and ISUP GG (Rho = 0.54, p < 0.001). In contrast, the PIRADS score displayed a sensitivity and specificity of 86% and 25% respectively, with a positive predictive value of 68%. No substantial correlation was found between PIRADS and ISUP GG. Statistical analysis revealed a significant correlation between PRIMARY and ISUP GG (p < 0.001), but not between PIRADS and ISUP GG (p = 0.281). Comparatively, PRIMARY scoring was significantly more reliable than PIRADS scoring in identifying csPCa. CONCLUSION: [68 Ga]Ga-PSMA-11 PET/CT imaging is promising for distinguishing high-risk prostate cancer patients from those apt for active surveillance, potentially aiding in the identification of csPCa.

Safety of transarterial radioembolization with Yttrium-90 glass microspheres without cystic artery occlusion.

PURPOSE: To assess radiation-induced cholecystitis in cases of cystic artery origin nearby the treatment zone for transarterial radioembolization (TARE) treatment. MATERIALS AND METHODS: Patients with primary or secondary malignant liver tumors treated with TARE, in whom cystic artery was located in the surrounding area of the treatment zone on 99m-technetium-MAA angiograms, were included in this study. Whole liver dose, tumor dose and healthy injected liver dose, lung dose and if applicable the gallbladder dose were all calculated by using the Medical Internal Radiation Dose (MIRD) formula from SPECT-CT images. Qualitative and quantitative assessment of the gallbladder was performed on SPECT-CT. The observed adverse events were classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE v5.0). RESULTS: A total of 34 TARE procedures from 29 patients (18 men and 11 women), with a mean age of 65 ± 13.3 years meeting the inclusion criteria, were involved in the current study. The mean tumor dose, healthy injected liver dose, healthy whole liver dose and gallbladder dose were 204.9 ± 66.8 Gy, 70.5 ± 15.7 Gy, 31.1 ± 12.7 Gy and 96.4 ± 53.4 Gy, respectively. The mean follow-up period was 14 ± 5.2 months. Qualitative assessment revealed gallbladder radioactivity on SPECT-CT in 11 (32.3%) patients with six mild and five moderate-severe radioactivities. There were no detected grade 2 or 3 adverse events. CONCLUSION: TARE is safely performed without cystic artery embolization when its origin is close to the treatment area.

Evaluation of the dosimetry approaches in ablation treatment of thyroid cancer.

In this study, we aimed to evaluate dosimetric approaches in ablation treatment of Differentiated Thyroid Carcinoma (DTC) without interrupting the clinical routine. Prior to therapy, 10.7 MBq 131 I in average was orally given to 24 patients suffering from DTC. MIRD formalism was used for dosimetric calculations. For blood and bone marrow dosimetry, blood samples and whole-body counts were collected at 2, 24, 72, and 120 h after I-131 administration. For remnant tissue dosimetry, uptake measurements were performed at the same time intervals. To estimate the remnant volume, anterior and lateral planar gamma camera images were acquired with a reference source within the field of view at 24 h after I-131 administration. Ultrasound imaging was also performed. Treatment activities determined with the fixed activity method were administered to the patients. Secondary cancer risk relative to applied therapy was evaluated for dosimetric approaches. The average dose to blood and bone marrow were determined as 0.15 ± 0.04 and 0.11 ± 0.04 Gy/GBq, respectively. The average remnant tissue dose was 0.58 ± 0.52 Gy/MBq and the corresponding required activity to ablate the remnant was approximately 1.3 GBq of 131 I. A strong correlation between 24th-hour uptake and time-integrated activity coefficient values was obtained. Compared to fixed activity method, approximately five times higher secondary cancer risk was determined in bone marrow dosimetry, while the risk was about three times lower in lesion-based dosimetry.

Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer.

PURPOSE: (177)Lu-617-prostate-specific membrane antigen (PSMA) ligand seems to be a promising tracer for radionuclide therapy of progressive prostate cancer. However, there are no published data regarding the radiation dose given to the normal tissues. The aim of the present study was to estimate the pretreatment radiation doses in patients who will undergo radiometabolic therapy using a tracer amount of (177)Lu-labeled PSMA ligand. METHODS: The study included seven patients with progressive prostate cancer with a mean age of 63.9 ± 3.9 years. All patients had prior PSMA positron emission tomography (PET) imaging and had intense tracer uptake at the lesions. The injected (177)Lu-PSMA-617 activity ranged from 185 to 210 MBq with a mean of 192.6 ± 11.0 MBq. To evaluate bone marrow absorbed dose 2-cc blood samples were withdrawn in short variable times (3, 15, 30, 60, and 180 min and 24, 48, and 120 h) after injection. Whole-body images were obtained at 4, 24, 48, and 120 h post-injection (p.i.). The geometric mean of anterior and posterior counts was determined through region of interest (ROI) analysis. Attenuation correction was applied using PSMA PET/CT images. The OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. RESULTS: The calculated radiation-absorbed doses for each organ showed substantial variation. The highest radiation estimated doses were calculated for parotid glands and kidneys. Calculated radiation-absorbed doses per megabecquerel were 1.17 ± 0.31 mGy for parotid glands and 0.88 ± 0.40 mGy for kidneys. The radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p < 0.05). The calculated radiation dose to bone marrow was 0.03 ± 0.01 mGy/MBq. CONCLUSION: Our first results suggested that (177)Lu-PSMA-617 therapy seems to be a safe method. The dose-limiting organ seems to be the parotid glands rather than kidneys and bone marrow. The lesion radiation doses are within acceptable ranges; however, there is a substantial individual variance so patient dosimetry seems to be mandatory.

Initial Findings on the Use of [225Ac]Ac-DOTATATE Therapy as a Theranostic Application in Patients with Neuroendocrine Tumors.

Objectives: This study aimed to evaluate the stability, safety, and efficacy of alpha-targeted therapy with [225Ac]Ac-DOTATATE in patients with grade 1/2 metastatic neuroendocrine tumors (NETs). Methods: This retrospective cohort included patients (n=11) with metastatic NETs from different primary sites (bronchial, pancreatic, nonpancreatic gastroenteropancreatic NETs, paraganglioma, and unknown primary site) treated with [225Ac]Ac-DOTATATE with a mean activity of 8.2±0.6 MBq (range: 7.5-10.0 MBq) at our institution between November 2019 and March 2022. The in vivo and in vitro stability of [225Ac]Ac-DOTATATE was calculated. The safety profile was evaluated according to the CTCAE-v5.0. Treatment efficacy was evaluated according to [68Ga] Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) images and the RECIST 1.1 criteria. Results: Patients had 73% (n=8) lymph node metastases, 91% (n=10) liver metastases, 36% (n=4) lung metastases, and 73% (n=8) bone metastases. All but one patient was refractory to treatment with [177Lu]Lu-DOTATATE. [225Ac]Ac-DOTATATE was stable for at least 5 h in vitro (in saline) and 3 h in vivo (urine and blood samples). Grade 2 renal toxicity and grade 2 hematotoxicity were observed in one patient. No grade 3-4 toxicities were reported. According to post-treatment [68Ga]Ga-DOTATATE PET/CT (n=9), 11% (n=1) had progressive disease, 44.4% (n=4) had stable disease, and 44.4% (n=4) had a partial response. The disease control rate was 89% (n=8). The median progression-free survival estimated according to Kaplan-Meier analysis was 12 months. Conclusion: The preliminary results of this study suggest that [225Ac]Ac-DOTATATE is stable, safe, and effective for treating advanced and [177Lu] Lu-DOTATATE-refractory NETs. However, prospective studies are needed to determine the impact of treatment on overall survival and to uncover potential side effects.

Clinical Experience with [225Ac]Ac-PSMA Treatment in Patients with [177Lu]Lu-PSMA-Refractory Metastatic Castration-Resistant Prostate Cancer.

For patients with advanced-stage metastatic castration-resistant prostate cancer (mCRPC) who do not respond to [177Lu]Lu-PSMA therapy, there are limited treatment options. Clinical results obtained with [225Ac]Ac-PSMA are promising. We retrospectively analyzed the outcomes of patients treated with [225Ac]Ac-PSMA between December 2018 and October 2022. Methods: We evaluated the treatment results of 23 patients (mean age, 70.3 ± 8.8 y) with mCRPC who were refractory to treatment with [177Lu]Lu-PSMA (2-9 cycles). The safety profile was assessed according to Common Technology Criteria for Adverse Events version 5.0. Treatment efficacy was assessed using prostate-specific membrane antigen PET progression criteria and prostate-specific antigen (PSA) response according to Prostate Cancer Working Group 2 criteria after the first cycle of [225Ac]Ac-PSMA treatment. Results: All patients received androgen-deprivation therapy, whereas 22 (96%) and 19 (83%) patients received chemotherapy and second-generation antiandrogen therapy, respectively. One patient received 4 cycles, 2 received 3 cycles, 8 received 2 cycles, and 12 received 1 cycle of [225Ac]Ac-PSMA. The median interval between cycles was 13 wk (range, 8-28 wk). [225Ac]Ac-PSMA was administered with a mean activity of 7.6 MBq (range, 6.2-10.0 MBq) in each cycle. Patients were at an advanced stage of disease, and tumor burden was very high. Although the best PSA response was observed in 5 patients (26%) after [225Ac]Ac-PSMA treatment, there was at least some level of decline in PSA observed in 11 patients (58%; n = 19). Treatment response was assessed in patients who underwent [68Ga]Ga-PSMA PET/CT imaging. After the first cycle of treatment (n = 18), 50% of patients (n = 9) showed disease progression according to prostate-specific membrane antigen PET progression criteria, and the disease control rate was calculated to be 50%. Median progression-free survival was 3.1 mo, and median overall survival was 7.7 mo. Grade 3 hematologic toxicity occurred in 1 patient, and grade 3 nephrotoxicity was observed in another patient. Parotid SUVmax decreased by 33%, although all patients complained of dry mouth before treatment. Conclusion: We observed that [225Ac]Ac-PSMA therapy was safe and showed potential even in cases with advanced-stage mCRPC in which all other treatment options were completed.

The Radiolabeling of [161Tb]-PSMA-617 by a Novel Radiolabeling Method and Preclinical Evaluation by In Vitro/In Vivo Methods.

Background: Prostate cancer (PC) is the most common type of cancer in elderly men, with a positive correlation with age. As resistance to treatment has developed, particularly in the progressive stage of the disease and in the presence of microfocal multiple bone metastases, new generation radionuclide therapies have emerged. Recently, [161Tb], a radiolanthanide introduced for treating micrometastatic foci, has shown great promise for treating prostate cancer. Results: In this study, Terbium-161 [161Tb]Tb was radiolabeled with prostate-specific membrane antigen (PSMA)-617 ([161Tb]-PSMA-617) and the therapeutic efficacy of the radiolabeled compound investigated in vitro and in vivo. [161Tb]-PSMA-617 was found to have a radiochemical yield of 97.99 ± 2.01% and was hydrophilic. [161Tb]-PSMA-617 was also shown to have good stability, with a radiochemical yield of over 95% up to 72 hours. In vitro, [161Tb]-PSMA-617 showed a cytotoxic effect on LNCaP cells but not on PC-3 cells. In vivo, scintigraphy imaging visualized the accumulation of [161Tb]-PSMA-617 in the prostate, kidneys, and bladder. Conclusions: The results suggest that [161Tb]-PSMA-617 can be an effective radiolabeled agent for the treatment of PSMA positive foci in prostate cancer.

Almost Complete Response with a Single Administration 225Ac-DOTATATE in a Patient with a Metastatic Neuroendocrine Tumor of Unknown Primary.

Neuroendocrine tumors (NETs) are being seen increasingly frequently, and the only known curative treatment method is surgical resection. Peptide receptor radionuclide therapy (PRRT) is a treatment option that the most contributes to progression-free survival and overall survival in metastatic cases.ß-emitting radionuclides are traditionally used for PRRT. Nowadays, alpha particle-emitting radionuclides are being developed, with advantages in terms of very high energy and a short path length, which should theoretically show higher efficacy. In this case; in a patient with NET diagnosis who had multiple (>50) lesions in the abdomen, almost all the lesions disappeared with a single dose application. This paper aims to present a case in which we observed the efficacy of 225Ac-DOTATATE treatment, which is an alpha treatment.

The anti-inflammatory effect of low-level laser therapy on experimentally induced inflammation of rabbit temporomandibular joint retrodiscal tissues.

AIMS: To investigate the effect of low-level laser therapy (LLLT) on experimentally induced inflammation in retrodiscal tissues of the rabbit temporo?mandibular joint (TMJ) using scintigraphic imaging. METHODS: Eleven male New Zealand rabbits were included in this study. Six randomly selected rabbits were imaged to provide normal joint images (normal group) before the initiation of the experiment. A 5% formalin solution was locally injected into both right and left TMJs of all rabbits. Subsequently, Ga-Al-As laser (wavelength: 815 nm; energy density: 12 J/cm2; output power: 250 mW) was applied for 48 seconds. The treatment was performed six times for 2 weeks to the left TMJ of all rabbits. The right TMJs of the rabbits were used as the control (nontreated) TMJ group, while left TMJs were used as the treated TMJ group. Static images of TMJ were taken at 24 hours, 7 days, and 14 days after the beginning of the treatment. The images of all TMJs were taken in the posteroanterior direction with the rabbit under sedation and its mouth open. The Mann-Whitney U test was used to compare group differences, and intragroup differences were determined by the Friedman test and Wilcoxon sign test. RESULTS: Significant differences were found between normal and both the control and treated TMJ groups. A reduction of inflammation in both treated and control TMJ groups was obtained, but there was no statistically significant difference between the groups. CONCLUSION: Under the conditions used in this study, quantitative scintigraphic measurements of TMJ inflammation of the treated TMJ group decreased but did not differ significantly from those of the control TMJ group.

Patient doses and dosimetric evaluations in interventional cardiology.

Interventional cardiological examinations may be associated with excessive radiation exposures which may cause skin injuries and higher probabilities of stochastic effects. Dose-area product (DAP) and skin doses of 325 patients were measured using alternative dosimetric techniques for different cardiological examinations. Data were collected from five different systems with the involvement of 11 cardiologists. All these dosimetric information has been collected separately for each of 10 projections together with the exposure parameters of X-ray systems. Mean DAP values measured with a transparent ion chamber were 49.1 Gy cm(2), 66.8 Gy cm(2), 106.9 Gy cm(2) and 124.7 Gy cm(2), respectively, for coronary angiography (CA), percutaneous transluminal coronary angioplasty (PTCA) or stent (PT-SI), coronary angiography and/or PTCA and/or stent (CA-PT-SI), and ablation examinations. Radiochromic films, thermoluminescent dosimeters (TLD) and point measurement of air kerma (AK) were carried out for skin dose assessments. Skin doses of 23 patients measured with radiochromic films were found to be between 2 Gy and 6 Gy. Although the complexity of the procedures was the major reason for these excessive doses, considerable contributions of high X-ray output of some fluoroscopy units were also noticed. In addition to the direct measurement of DAP, alternative DAP values were also determined from the skin dose measurement techniques; exposed areas were summed on digitized radiochromic films in one technique, The product of AK reading with X-ray field size measured at the patient entrance using slow X-ray films was taken as another DAP. Good correlations were found among the DAP results and also between the entrance skin doses calculated from AK measurements and direct DAP readings (R(2)=0.91). A trigger DAP value of 130 Gy cm(2) for the 2 Gy of skin doses was derived from this relationship. Collection of dosimetric data for each projection was also investigated regarding a possible standardization of clinical techniques; in the case of coronary angiography examinations LAO 45 and RAO 30 were found as the dominant projections which may also simplify the dosimetric technique.

Investigating the effect of dental implant materials with different densities on radiotherapy dose distribution using Monte-Carlo simulation and pencil beam convolution algorithm.

OBJECTIVES: The aim of this study was to investigate the effect of dental implant materials with different physical densities on dose distribution for head and neck cancer radiotherapy planning. METHODS: Titanium (Ti), Titanium alloy (Ti-6Al-4V), Zirconia (Y-TZP), Zirconium oxide (ZrO2), Alumina (Al2O3) and polyetheretherketone (PEEK) dental implant materials were used for determination of implant material effect on dose distribution. Dental implant effect was investigated by using pencil beam convolution (PBC) algorithm of Eclipse treatment planning systems (TPS) and Monte Carlo (MC) simulation technique. 6 MV photon beam of the Varian 2300 C/D linear accelerator was simulated by EGSnrc-based BEAMnrc MC code system. RESULTS: Reasonable consistency was determined for percentage depth dose (PDD) curves between MC simulation and water phantom measurements at 6.4 MeV initial electron energy. The consistency between modelled linear accelerator PDD curve calculations and water-phantom PDD measurements were compatible within 1 % range. The dose increase in front of the dental implant calculated by MC simulation is in the range of 0.4-20.2%. We found by MC and PBC calculations that the differences in dose increase in front of the dental implant materials is in the range of 0.1-17.2% and is dependent on the physical density of the dental implant. CONCLUSIONS: Dose increase for Zirconia was noted to be maximum while PEEK implant dose increase was minimum among the whole dental implant materials studied. This study revealed that the Eclipse TPS PBC algorithm could not accurately estimate the backscatter radiation from dental implant materials.

Effects of radiologists' skill and experience on patient doses in interventional examinations.

In this study, effects of radiologists' skill and experience on patient doses were investigated. Dose-area product and entrance surface doses of two groups of patients, one examined by a number of junior radiologists and another one by a senior radiologist, have been compared for the diagnostic interventional examinations of cerebral and lower limbs. Collimation of the X-ray beam and shortening the fluoroscopy times by the senior radiologist considerably reduced the patient doses for interventional cerebral examinations.

Investigation of mean glandular dose versus compressed breast thickness relationship for mammography.

The relationship between the mean glandular dose (MGD) and the compressed breast thickness (CBT) is commonly used for the presentation of mammographic dose survey results and could also be useful for the assessment of individual breast doses retrospectively in case of lack of necessary dosimetric instrumentation. The high data scattering from the best fit reduces the reliability of this technique. The aim of this study was to investigate the accuracy of this relationship using the data collected from a patient survey and phantom experiment. Patients were divided into three different groups according to their breast glandularities, which were predicted from the inspection of previous mammograms. X-ray beam qualities that will be used in patient examinations were determined according to breast thickness and predicted glandularities. The MGD versus CBT relationship for all the examined patients resulted in a poor correlation (R2 = 0.28). This relationship was separately obtained for each glandularity group and also for sub-groups of specific beam qualities. The best correlation (R(2) = 0.73) was obtained for the fatty breast group and Mo/Mo combination. A low correlation (R2 = 0.34) was observed in the mid-glandularity group due to inclusion of a wide range of glandularities in this group. In the case of the dense breast group, although the glandularity range was narrow, there were e still high data scattering (R2 = 0.25). This was probably due to the use of Mo/Rh and Mo/Mo combinations. This is validated by obtaining the MGD-CBT relationship specific to Mo/Mo combination (R2 = 0.61).

ESTIMATION OF THE ORGAN ABSORBED DOSES AND EFFECTIVE DOSE FROM 68Ga-PSMA-11 PET SCAN.

68Ga-PSMA-11 PET/CT has been proven to have high clinical value for imaging of prostate cancer and rapidly gained popularity. In this study, we aimed to investigate absorbed doses of 68Ga-PSMA-11. Seven patients (mean age = 66.9 ± 6.6 years, range: 57-79 years) were enrolled in the study. Whole body PET images were acquired with multiple time points. MIRD method, NUKFIT and OLINDA/EXM software were used for dosimetry calculations. Kidneys, bladder wall, salivary and lacrimal glands received the highest absorbed dose. Estimated absorbed doses to these organs after injection of 150 MBq 68Ga-PSMA-11 were 37.0, 12.6, 14.4 and 6.3 mSv, respectively. Effective dose from PET scanning with 150 MBq injected 68Ga-PSMA-11 was 2.5 mSv. In conclusion, 68Ga-PSMA-11 has a favorable dosimetry profile similar to the 68Ga labeled octreotide analogs, which are used safely in routine clinical practices for many years. No adverse effects were reported. The kidneys were the dose-limiting organs.

Evaluation of PET Scanner Performance in PET/MR and PET/CT Systems: NEMA Tests.

OBJECTIVE: The aim of the present study was to compare the performance of positron emission tomography (PET) component of PET/computed tomography (CT) with new emerging PET/magnetic resonance (MR) of the same vendor. METHODS: According to National Electrical Manufacturers Association NU2-07, five separate experimental tests were performed to evaluate the performance of PET scanner of General Electric GE company; SIGNATM model PET/MR and GE Discovery 710 model PET/CT. The main investigated aspects were spatial resolution, sensitivity, scatter fraction, count rate performance, image quality, count loss and random events correction accuracy. RESULTS: The findings of this study demonstrated superior sensitivity (~ 4 folds) of PET scanner in PET/MR compared to PET/CT system. Image quality test exhibited higher contrast in PET/MR (~ 9%) compared with PET/CT. The scatter fraction of PET/MR was 43.4% at noise equivalent count rate (NECR) peak of 218 kcps and the corresponding activity concentration was 17.7 kBq/cc. Whereas the scatter fraction of PET/CT was found as 39.2% at NECR peak of 72 kcps and activity concentration of 24.3 kBq/cc. The percentage error of the random event correction accuracy was 3.4% and 3.1% in PET/MR and PET/CT, respectively. CONCLUSION: It was concluded that PET/MR system is about 4 times more sensitive than PET/CT, and the contrast of hot lesions in PET/MR was ~ 9% higher than PET/CT. These outcomes also emphasize the possibility to achieve excellent clinical PET images with low administered dose and/or a short acquisition time in PET/MR.

177Lu-DOTATATE therapy in patients with neuroendocrine tumours including high-grade (WHO G3) neuroendocrine tumours: response to treatment and long-term survival update.

PURPOSE: Upon diagnosis, distant metastases are encountered in 21-50% of neuroendocrine tumours (NETs). However, few systemic treatment options are available for the well-differentiated NETs in the metastatic stage. Lu-DOTATATE is one of the most effective treatments in this limited patient group. We retrospectively investigated its efficacy and effect on the survival in patients with both well-differentiated and grade III NETs who had high uptake in pretherapeutic Ga-DOTATATE PET/computed tomography scans. PATIENTS AND METHODS: Patients with metastatic NETs treated with Lu-DOTATATE between January 2010 and November 2015 in our department were included in this retrospective cohort. Toxicity and adverse effects were evaluated according to SWOG criteria. Progression-free survival (PFS) and overall survival (OS) rates were calculated considering the first date of treatment. Response was evaluated according to RECIST criteria. Potential predictors of survival and response were analysed. RESULTS: Patients (n=186) with metastatic NETs originating from various primary sites (bronchial, pancreatic, nonpancreatic gastroenteropancreatic-NETs, pheochromocytoma-paraganglioma and unknown primary) were treated with 1107 courses of Lu-DOTATATE treatment (median: 6; range: 3-12). Among 160 patients whose responses to treatment could be evaluated according to the RECIST criteria, 28.1% (n=45) had a progressive disease, 21.9% (n=35) had a stable disease, 46.9% (n=75) had a partial response and 3.1% (n=5) had a complete response. Median follow-up was 30.6 months. The Kaplan-Meier estimated median PFS was 36.4 months, mean PFS was 38 months and the mean OS was 55 months. The disease control rates in patients with WHO grades I, II and III were 74, 73 and 60%, respectively, and the OS rates were 61.9, 52.2 and 38.4 months, respectively. We observed no major renal toxicity except a minor increase (11.1%) in average serum creatinine levels. In 33.9% (n=56) of the patients, grade I toxicity; in 9.1% (n=15), grade II; and in 1.2% (n=2), grade III toxicity were observed. CONCLUSION: Lu-DOTATATE therapy is an important treatment option in somatostatin receptor type-2-positive pancreatic, nonpancreatic gastroenteropancreatic-NETs, and lung NETs including metastatic NETs with an unknown primary site and significantly contributed to patients' OS. Additionally, peptide receptor radionuclide therapy may have a role in a selected subgroup of patients with grade III NET with high somatostatin receptor type-2 expression.

Lu-177-PSMA-617 Prostate-Specific Membrane Antigen Inhibitor Therapy in Patients with Castration-Resistant Prostate Cancer: Stability, Bio-distribution and Dosimetry.

OBJECTIVE: The aim of the study was to estimate the radiation-absorbed doses and to study the in vivo and in vitro stability as well as pharmacokinetic characteristics of lutetium-177 (Lu-177) prostate-specific membrane antigen (PSMA)-617. METHODS: For this purpose, 7 patients who underwent Lu-177-PSMA therapy were included into the study. The injected Lu-177-PSMA-617 activity ranged from 3.6 to 7.4 GBq with a mean of 5.2±1.8 GBq. The stability of radiotracer in saline was calculated up to 48 h. The stability was also calculated in blood and urine samples. Post-therapeutic dosimetry was performed based on whole body and single photon emission computed tomography/computed tomography (SPECT/CT) scans on dual-headed SPECT/CT system. RESULTS: The radiochemical yield of Lu-177-PSMA-617 was >99%. It remained stable in saline up to 48 h. Analyses of the blood and urine samples showed a single radioactivity peak even at 24 hours after injection. Half-life of the distribution and elimination phases were calculated to be 0.16±0.09 and 10.8±2.5 hours, respectively. The mean excretion rate was 56.5±8.8% ranging from 41.5% to 65.4% at 24 h. Highest radiation estimated doses were calculated for parotid glands and kidneys (1.90±1.19 and 0.82±0.25 Gy/GBq respectively). Radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p<0.05) (0.030±0.008 Gy/GBq). CONCLUSION: Lu-177-PSMA-617 is a highly stable compound both in vitro and in vivo. Lu-177-PSMA-617 therapy seems to be a safe method for the treatment of castration-resistant prostate cancer patients. The fractionation regime that enables the longest duration of tumor control and/or survival will have to be developed in further studies.

Comparison of metabolic and anatomic response to chemotherapy based on PERCIST and RECIST in patients with advanced stage non-small cell lung cancer.

BACKGROUND: The aim of this study was to explore the prognostic role of metabolic response to chemotherapy, determined by FDG-PET, in patients with metastatic non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Thirty patients with metastatic NSCLC were analyzed for prognostic factors related to overall survival (OS) and progression free survival (PFS). Disease evaluation was conducted with FDG-PET/CT and contrast-enhanced CT prior to and at the end of first-line chemotherapy. Response evaluation of 19 of 30 patients was also performed after 2-3 cycles of chemotherapy. Morphological and metabolic responses were assessed according to RECIST and PERCIST, respectively. RESULTS: The median OS and PFS were 11 months and 6.2 months, respectively. At the end of first-line chemotherapy, 10 patients achieved metabolic and anatomic responses. Of the 19 patients who had an interim response analysis after 2-3 cycles of chemotherapy, 3 achieved an anatomic response, while 9 achieved a metabolic response. In univariate analyses, favorable prognostic factors for OS were number of cycles of first-line chemotherapy, and achieving a response to chemotherapy at completion of therapy according to the PERCIST and RECIST. The OS of patients with a metabolic response after 2-3 cycles of chemotherapy was also significantly extended. Anatomic response at interim analysis did not predict OS, probably due to few patients with anatomic response. In multivariate analyses, metabolic response after completion of therapy was an independent prognostic factor for OS. CONCLUSIONS: Metabolic response is at least as effective as anatomic response in predicting survival. Metabolic response may be an earlier predictive factor for treatment response and OS in NSCLC patients.

Variations of patient doses in interventional examinations at different angiographic units.

PURPOSE: We analyzed doses for various angiographic procedures using different X-ray systems in order to assess dose variations. METHODS: Dose-area product (DAP), skin doses from thermoluminescent dosimeters and air kerma measurements of 308 patients (239 diagnostic and 69 interventional) were assessed for five different angiographic units. All fluoroscopic and radiographic exposure parameters were recorded online for single and multiprojection studies. Radiation outputs of each X-ray system were also measured for all the modes of exposure using standard protocols for such measurements. RESULTS: In general, the complexity of the angiographic procedure was found to be the most important reason for high radiation doses. Skill of the radiologist, management of the exposure parameters and calibration of the system are the other factors to be considered. Lateral cerebral interventional studies carry the highest risk for deterministic effects on the lens of the eye. Effective doses were calculated from DAP measurements and maximum fatal cancer risk factors were found for carotid studies. CONCLUSIONS: Interventional radiologists should measure patient doses for their examinations. If there is a lack of necessary instrumentation for this purpose, then published dose reports should be used in order to predict the dose levels from some of the exposure parameters. Patient dose information should include not only the measured quantity but also the measured radiation output of the X-ray unit and exposure parameters used during radiographic and fluoroscopic exposures.