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.

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.

Interobserver and intraobserver agreement on prostate-specific membrane antigen PET/CT images according to the miTNM and PSMA-RADS criteria.

AIM: In this study, we aimed to measure interobserver and intraobserver agreement in Ga-68-prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) image interpretation. In addition, the limitations of these criteria and levels of personal confidence reported by the readers when reporting the findings were determined. The effects of interpersonal differences on clinical decisions were also investigated. METHODS: PSMA PET images from 133 cases were reported independently by four different readers at different times according to the molecular imaging TNM (miTNM) and PSMA-reporting and data system (RADS) templates. RESULTS: There was substantial interobserver agreement for overall positivity, miT, miN and miM staging (Fleiss' κ = 0.65, 0.625, 0.731, and 0.779). Substantial agreement levels were observed in reporting of seminal vesicle invasion, the number of lymph node stations with metastasis, total number of intraprostatic areas containing tumors, and lymph node metastasis staging (Fleiss' κ = 0.622 and 0.779). The highest variation was seen in the reporting of intraprostatic distribution: In International Society of Urological Pathology (ISUP) grade group 1, moderate agreement was observed, and it was seen that the agreement level for the T staging increased with an increasing ISUP group in the staging group (Fleiss' κ = 0.531 vs. 0.655). There was near-perfect interobserver agreement in the reporting of five-point PSMA-RADS scoring [intraclass correlation coefficient (ICC) κ = 0.904; 95% CI, 0.865-0.934]. Disagreement according to miTNM staging had a major effect on clinical management in only 9% (n = 12) of the patients. CONCLUSION: PSMA PET has a lower interobserver variability and higher reproducibility than other imaging methods used for imaging of prostate cancer do, including CT, MRI, and bone scintigraphy. The miTNM template provides a reporting format that is highly reproducible and has a high level of agreement among readers, but the prostatic template needs development. In contrast, the PSMA-RADS system leads to slightly increased interobserver reporting differences and reduces personal confidence, but at the same time, it still exhibits almost-perfect agreement in terms of scoring.

Myelodysplastic Syndrome Presenting With Diffuse Bone Marrow Uptake on 68Ga-PSMA PET/CT.

We present the case of a 67-year-old man with prostate cancer who had no findings of recurrence, except diffuse radiotracer uptake in the bone marrow in Ga-PSMA PET/CT. Bone marrow uptake was also represented as multiple focal increased spots without any corresponding lytic or sclerotic lesions in CT. MRI revealed a high and homogeneous T2 signal within the bone marrow, without any contrast-enhanced or diffusion-restricted lesions. Further workup, including a bone marrow biopsy, revealed the diagnosis of myelodysplastic syndrome.

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.

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 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.

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.

Multifoci Bone Tuberculosis and Lymphadenitis in Mediastinum Mimics Malignancy on FDG-PET/CT: A Case Report.

UNLABELLED: Positron Emission Tomography with 2-deoxy-[F-18]-fluoro-D-glucose (FDG-PET) has become a reliable diagnostic tool in clinical practice similar to Magnetic Resonance (MR) imaging and Computed Tomography (CT). FDG-PET has especially been used to differentiate malignant from benign lesions, and for staging and follow- up malignant tumors. However, FDG-PET has some pitfalls in cancer screening and FDG tracer accumulates at sites of infection and inflammation. Bone tuberculosis may be confused with malignant tumors of bone and its metastases, and can accumulate focally increased FDG in active period. We present a 60-year-old woman with lytic bone lesions and mediastinal hypermetabolic foci, initially suspected to be malignant by means of FDG-PET and the other imaging modalities; however, bone biopsy confirmed the diagnosis of bone tuberculosis. CONFLICT OF INTEREST: None declared.