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.

Leukocyte Labeling with Tc-99m-HMPAO: The Role of Leucocyte Numbers and Medication on the Labeling Efficacy and Image Quality.

Objectives: The aim of this study is to evaluation of Tc-99m-hexamethylpropyleneamineoxime (HMPAO)-labeled leukocytes in terms of radiochemical, biochemical, and microbiological quality controls and to examine the effect of leukocyte numbers of the blood obtained from patients and the medications currently used by the patients on the radiochemical yields of Tc-99m-HMPAO-labeled leukocytes, and imaging quality was evaluated. Methods: Thirty paients were included in our study who applied to Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Department of Nuclear Medicine for Tc-99m-HMPAO-labeled leukocyte scintigraphy. Devices and chemicals used in the preparation of Tc-99m-HMPAO-labeled laukocytes were compared with other nuclear medicine clinics. Tc-99m-HMPAO-labeled leukocytes were evaluated in terms of radiochemical, biochemical, and microbiological quality controls. The effect of leukocyte numbers of the blood obtained from patients and the medications currently used by the patients on the radiochemical yields of Tc-99m-HMPAO-labeled leukocytes and imaging quality was evaluated. Results: The pH range of Tc-99m-HMPAO was 6-8 and the radiochemical purity was 90±2.04% (n=30), the radiochemical yield of Tc-99m-HMPAO-labeled leukocytes was 51±2.18% (n=30), the radiolabeling yield of Tc-99m-HMPAO-labeled leukocyte increased as the amount of white blood cell in the blood increased and whether the patients used any antibiotic, blood thinners, insulin and blood pressure medications did not affect the radiolabeling yield of Tc-99m-HMPAO-labeled leukocytes. The number of erythrocytes were removed at a rate of >99% in LPR by starch solution (6% HES; in the hemocytometric examination of Tc-99m-HMPAO-labeled leukocytes performed zeroth and 4th h, living/dead cell ratio was found 97.5% and the product was sterile. Conclusion: Tc-99m-HMPAO was labeled with leukocytes successfully, and Tc-99m-HMPAO-labeled leukocytes was safely injected to the patients as sterile without loss of vitality and aggregation.

Development and validation of a UV-Radio-HPLC method to assess chemical and radiochemical purity of [68Ga] Ga-PSMA-11.

[68Ga]Ga-PSMA-11, a urea-based peptidomimetic, has been widely used in recent years for PET imaging of patients with prostate cancer. Since it has short half-life and should be in-house synthesized, synthesis conditions may affect quality and in vivo behavior of [68Ga]Ga-PSMA-11. Therefore in this study we aimed to develop an alternative, simple and validated HPLC method to test chemical and radiochemical purity of [68Ga]Ga-PSMA-11 for clinical routine.

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.

EANM guideline on quality risk management for radiopharmaceuticals.

This document is intended as a supplement to the EANM "Guidelines on current Good Radiopharmacy Practice (cGRPP)" issued by the Radiopharmacy Committee of the EANM (Gillings et al. in EJNMMI Radiopharm Chem. 6:8, 2021). The aim of the EANM Radiopharmacy Committee is to provide a document that describes how to manage risks associated with small-scale "in-house" preparation of radiopharmaceuticals, not intended for commercial purposes or distribution.

Evaluation of F-18 DOPA PET/CT in the detection of recurrent or metastatic medullary thyroid carcinoma: comparison with GA-68 DOTA-TATE PET/CT.

OBJECTIVE: PET imaging with F-18 DOPA (FDOPA) and Ga-68 DOTATATE (TATE) shows the most promising results to detect medullary thyroid cancer (MTC) recurrence. We performed this comparative study to detect the site of recurrent or metastatic disease in MTC patients with elevated serum calcitonin (Ctn) and/or carcinoembryonic antigen (CEA) levels. METHODS: We studied 46 MTC patients (25 women, 21 men) with elevated Ctn and/or CEA levels during follow-up who had both FDOPA and TATE PET/CT scans for re-staging purposes. RESULTS: FDOPA PET imaging yielded an overall sensitivity of 86.8%, specificity of 100%, PPV of 100%, NPV of 61.5%, and accuracy of 89.1%, while TATE PET scan had the same values as 84.2%, 87.5%, 96.9%, 53.8%, and 84.6%, respectively, and there was no statistically significant difference between the two modalities with the exception of the specificity value that was higher for FDOPA imaging. In a subgroup of patients with overt Ctn or CEA elevation, sensitivity of FDOPA increased significantly, whereas TATE sensitivity did not change. FDOPA PET imaging was significantly superior in detecting liver and regional lymph node (LN) metastases, while TATE PET scan was significantly better in the skeletal metastases. Early FDOPA demonstrated 11 invisible lesions on late FDOPA. CONCLUSION: Both FDOPA and TATE PET/CT imaging are useful to localize recurrences in MTC patients. While TATE imaging is superior to reveal skeletal disease, FDOPA seems better in liver and regional LN metastases; therefore, the two modalities appear complementary in monitoring MTC patients with elevated serum Ctn and/or CEA levels.

Guideline on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals.

This guideline on current good radiopharmacy practice (cGRPP) for small-scale preparation of radiopharmaceuticals represents the view of the Radiopharmacy Committee of the European Association of Nuclear Medicine (EANM). The guideline is laid out in the format of the EU Good Manufacturing Practice (GMP) guidelines as defined in EudraLex volume 4. It is intended for non-commercial sites such as hospital radiopharmacies, nuclear medicine departments, research PET centres and in general any healthcare establishments. In the first section, general aspects which are applicable to all levels of operations are discussed. The second section discusses the preparation of small-scale radiopharmaceuticals (SSRP) using licensed generators and kits. Finally, the third section goes into the more complex preparation of SSRP from non-licensed starting materials, often requiring a purification step and sterile filtration. The intention is that the guideline will assist radiopharmacies in the preparation of diagnostic and therapeutic SSRP's safe for human administration.

The Role of 68GA-PSMA PET/CT Scan In Patients with Prostate Adenocarcinoma who Underwent Radical Prostatectomy.

PURPOSE: To determine whether a 68Ga-PSMA PET/CT scan evaluation before radical prostatectomy (RP) is an effective imaging modality for clinical local and lymph node (LN) staging compared with the pathological results. MATERIALS AND METHODS: We performed a preoperative 68Ga-PSMA PET/CT scan in 51 patients with prostate cancer (PCa), who were scheduled for an RP operation between January 2014 and June 2016 in our clinic. The correlation between the RP pathology and the results of the 68Ga-PSMA PET/CT scan was investigated. RESULTS: When the 68Ga-PSMA PET/CT scan results were evaluated according to the risk groups, intraprostatic activity was found in 5 of 12 patients (41.7%) in the low-risk group, 15 of 19 patients in the intermediate risk group (78.9%), and 90% patients in the high-risk group. The 68Ga-PSMA PET/CT scan sensitivity, specificity, positive and negative predictive values and accuracy were calculated as 58.2%, 75.3%, 84.4%, 44%, and 63%, respectively for intraprostatic tumor localization; 68.4%, 75%, 61.9%, 80%, and %72.6%, respectively for extracapsular extension; 63.6%, 92.3%, 70%, 90%, and 86%, respectively for seminal vesicle involvement; 50%, 100%, 100%, 88%, and 89.3%, respectively for LN metastasis. CONCLUSION: The 68Ga-PSMA PET/CT scan accurately demonstrates intraprostatic tumor localization in high-risk group and presence of seminal vesicle involvement, which can help to accurately detect the target lesion before prostate biopsy. In addition, with its high sensitivity and specificity values, 68Ga-PSMA PET/CT is a valuable imaging method for the assessment of LN metastasis in intermediate- and high-risk groups and also provides accurate nodal staging before RP.

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.

EANM guideline on the validation of analytical methods for radiopharmaceuticals.

BACKGROUND: To fulfil good manufacturing requirements, analytical methods for the analysis of pharmaceuticals for human and vetinary use must be validated. The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has published guidance documents on the requirements for such validation activities and these have been adopted by the European Medicines Agency, The U.S. Food and Drug Administration (FDA) and other regulatory bodies. These guidance documents do not, however, fully address all the specific tests required for the analysis of radiopharmaceuticals. This guideline attempts to rectify this shortcoming, by recommending approaches to validate such methods. RESULTS: Recommedations for the validation of analytical methods which are specific for radiopharmaceutials are presented in this guideline, along with two practical examples. CONCLUSIONS: In order to comply with good manufacturing practice, analytical methods for radiopharmaceuticals for human use should be validated.

Performance of F-18 Fluorocholine PET/CT for Detection of Hyperfunctioning Parathyroid Tissue in Patients with Elevated Parathyroid Hormone Levels and Negative or Discrepant Results in conventional Imaging.

OBJECTIVE: Our aim was to assess the diagnostic performance of F-18 fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) in detecting hyperfunctioning parathyroid tissue (HPT) in patients with elevated parathyroid hormone levels with negative or inconclusive conventional imaging results and to compare the findings with those obtained using technetium-99m sestamibi (MIBI) scintigraphy and neck ultrasonography (US). MATERIALS AND METHODS: Images of 105 patients with hyperparathyroidism who underwent FCH PET/CT, dual-phase MIBI parathyroid scintigraphy (median interval: 42 days), and neck US were retrospectively analyzed. The gold standard was histopathological findings for 81 patients who underwent parathyroidectomy and clinical follow-up findings in the remaining 24 patients. Sensitivities, positive predictive values (PPVs), and accuracies were calculated for all imaging modalities. RESULTS: Among the 81 patients who underwent parathyroidectomy, either parathyroid adenoma (n = 64), hyperplasia (n = 9), neoplasia (n = 4), or both parathyroid adenoma and hyperplasia (n = 1) were detected, except 3 patients who did not show HPT. Of the 24 (23%) patients who were followed-up without operation, 22 (92%) showed persistent hyperparathyroidism. FCH PET/CT showed significantly higher sensitivity than MIBI scintigraphy and US in detection of HPT (p < 0.01). Sensitivity, PPV, and accuracy of FCH PET/CT were 94.1% (95/101), 97.9% (95/97), and 92.4% (97/105), respectively. The corresponding values for MIBI scintigraphy and US were 45.1% (46/102), 97.9% (46/47), and 45.7% (48/105) and 44.1% (45/102), 93.8% (45/48), and 42.9% (45/105), respectively. Among the 35 patients showing negative MIBI scintigraphy and neck US findings, 30 (86%) showed positive results on FCH PET/CT. FCH PET/CT could demonstrate ectopic locations of HPT in 11 patients whereas MIBI and US showed positive findings in only 6 and 3 patients, respectively. CONCLUSION: FCH PET/CT is an effective imaging modality for detection of HPT with the highest sensitivity among the available imaging techniques. Therefore, FCH PET/CT can be recommended especially for patients who show negative or inconclusive results on conventional imaging.

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.

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.

64Cu-Labeled Phosphonate Cross-Bridged Chelator Conjugates of c(RGDyK) for PET/CT Imaging of Osteolytic Bone Metastases.

OBJECTIVE: The goal of this research was to evaluate c(RGDyK) conjugated to phosphonate-based cross-bridged chelators using Cu-free click chemistry in the 4T1 mouse mammary tumor bone metastasis model in comparison with 64Cu-CB-TE2A-c(RGDyK), which previously showed selective binding to integrin αvß3 on osteoclasts. EXPERIMENTAL: Two phosphonate-based cross-bridged chelators (CB-TE1A1P and CB-TE1K1P) were conjugated to c(RGDyK) through bio-orthogonal strain-promoted alkyne-azide cycloaddition. In vitro and in vivo evaluation of the 64Cu-labeled TE1A1P-DBCO-c(RGDyK) (AP-c(RGDyK)), TE1K1P-PEG4-DBCO-c(RGDyK) (KP-c(RGDyK)), and CB-TE2A-c(RGDyK) were compared in the 4T1 mouse model of bone metastasis. The affinities of the unconjugated and chelator-c(RGDyK) analogs for αvß3 integrin were determined using a competitive-binding assay. For in vivo evaluation, BALB/c mice were injected with 1 × 105 4T1/Luc cells in the left ventricle. Formation of metastases was monitored by bioluminescence imaging (BLI) followed by small-animal PET/CT 2 h postinjection of radiotracers. RESULTS: The chelator-peptide conjugates showed similar affinity to integrin αvß3, in the low nM range. PET imaging demonstrated a higher uptake in bones having metastases for all 64Cu-labeled c(RGDyK) analogs compared with bones in nontumor-bearing mice. The correlation between uptake of 64Cu-AP-c(RGDyK) and 64Cu-KP-c(RGDyK) in bones with metastases based on PET/CT imaging, and osteoclast number based on histomorphometry, was improved over the previously investigated 64Cu-CB-TE2A-c(RGDyK). CONCLUSION: These data suggest that the phosphonate chelator conjugates of c(RDGyK) peptides are promising PET tracers suitable for imaging tumor-associated osteoclasts in bone metastases.

The accuracy of 68Ga-PSMA PET/CT in primary lymph node staging in high-risk prostate cancer.

PURPOSE: To assess the diagnostic accuracy of 68Ga-PSMA PET in predicting lymph node (LN) metastases in primary N staging in high-risk and very high-risk nonmetastatic prostate cancer in comparison with morphological imaging. METHODS: This was a multicentre trial of the Society of Urologic Oncology in Turkey in conjunction with the Nuclear Medicine Department of Cerrahpasa School of Medicine, Istanbul University. Patients were accrued from eight centres. Patients with high-risk and very high-risk disease scheduled to undergo surgical treatment with extended LN dissection between July 2014 and October 2015 were included. Either MRI or CT was used for morphological imaging. PSMA PET/CT was performed and evaluated at a single centre. Sensitivity, specificity and accuracy were calculated for the detection of lymphatic metastases by PSMA PET/CT and morphological imaging. Kappa values were calculated to evaluate the correlation between the numbers of LN metastases detected by PSMA PET/CT and by histopathology. RESULTS: Data on 51 eligible patients are presented. The sensitivity, specificity and accuracy of PSMA PET in detecting LN metastases in the primary setting were 53%, 86% and 76%, and increased to 67%, 88% and 81% in the subgroup with of patients with ≥15 LN removed. Kappa values for the correlation between imaging and pathology were 0.41 for PSMA PET and 0.18 for morphological imaging. CONCLUSIONS: PSMA PET/CT is superior to morphological imaging for the detection of metastatic LNs in patients with primary prostate cancer. Surgical dissection remains the gold standard for precise lymphatic staging.

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.

Preclinical Evaluation of 18F-ML-10 to Determine Timing of Apoptotic Response to Chemotherapy in Solid Tumors.

PURPOSE: We investigated 2-(5-fluoro-pentyl)-2-methyl-malonic acid (18F-ML-10) positron emission tomography (PET) imaging of apoptosis posttherapy to determine optimal timing for predicting chemotherapy response in a mouse head/neck xenograft cancer model. PROCEDURES: BALB/c nude mice (4-8 weeks old) were implanted with UM-SCC-22B tumors. The treatment group received 2 doses of doxorubicin (10 mg/kg, days 0, 2). Small animal 18F-ML-10 PET/computed tomography was performed before and on days 1, 3, and 7 postchemotherapy. Using regions of interest around tumors, 18F-ML-10 uptake change was measured as %ID/g and uptake relative to liver. Terminal Uridine Nick-End Labeling (TUNEL) immunohistochemistry assay was performed using tumor samples of baseline and on days 1, 3, and 7 posttreatment. RESULTS: Treated mice demonstrated increased 18F-ML-10 uptake compared to baseline and controls, and 10 of 13 mice showed tumor volume decreases. All control mice showed tumor volume increases. Tumor-to-liver (T/L) ratios from the control group mice did not show significant change from baseline ( P > .05); however, T/L ratios of the treatment group showed significant 18F-ML-10 uptake differences from baseline compared to days 3 and 7 posttreatment ( P < .05), but no significant difference at 1 day posttreatment. CONCLUSION: 2-(5-Fluoro-pentyl)-2-methyl-malonic acid PET imaging has the potential for early assessment of treatment-induced apoptosis. Timing and image analysis strategies may require optimization, depending on the type of tumor and cancer treatment.