Immune Response to Molecular Radiotherapy with 177Lu-DOTATOC: Predictive Value of Blood Cell Counts for Therapy Outcome.

Purpose: In a prior, retrospective study, 76% of patients with advanced neuroendocrine tumors undergoing 177Lu-DOTATOC molecular radiotherapy (MRT) showed their best response within 8 months from the first MRT cycle. In 24% of patients, latency was much greater up to >22 months after the first cycle, and long after near-complete decay of 177Lu from the last cycle. An immune response induced by MRT seems a likely explanation. As a crude measure of immunocompetence, the authors investigated whether blood cell counts (BCCs) may have predictive value for MRT outcome with 177Lu-DOTATOC. Methods: 56 Patients with neuroendocrine tumors (NET) were administered 177Lu-DOTATOC (mean 2.1 cycles; range 1-4) with median radioactivity of 7.0 GBq/cycle at 3-month intervals. Patients' BCCs were evaluated for four responder categories: CR, PR, SD, and PD (RECIST 1.1). Furthermore, baseline BCCs were correlated with progression-free survival (PFS). Finally, BCCs of patients with (PMT+) and without prior medical therapy (PMT-) were compared. Results: Significant differences between responder categories were found for baseline hemoglobin (Hb), erythrocytes, neutrophils, lymphocytes, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and LEHN-score, integrating lymphocyte, erythrocyte, and neutrophil counts, and Hb level, but not for leukocytes and platelets. LEHN-score yielded an almost complete separation between CR and PD groups. In analogy, PFS times showed significant correlations with baseline Hb, erythrocytes, neutrophils, lymphocytes, NLR, PLR, and LEHN-score, the LEHN-score showing the strongest correlation, but not with leukocytes and platelets. For PMT- patients, median PFS was 34.5 months, compared with 20.8 months in PMT+ patients, with corresponding baseline lymphocyte (32.1 ± 9.6% vs. 24.5 ± 11.6%, p = 0.028) and neutrophil (54.9 ± 11.6% vs. 63.5 ± 13.7%, p = 0.039) counts. Conclusion: These findings emphasize the significance of an immune response to MRT for obtaining optimal therapy efficacy and support concepts to enhance the immune response of less immunocompetent patients before MRT. It seems advisable to avoid prior or concomitant immunosuppressant medical therapy.

Peptide Receptor Radionuclide Therapy in Patients With Advanced Progressive Medullary Thyroid Cancer: Efficacy, Safety, and Survival Predictors.

PURPOSE: Progressive metastatic medullary thyroid carcinoma (MTC) is often characterized by rapid disease progression and poor prognosis, with only few therapeutic options available. Peptide receptor radionuclide therapy (PRRT) has demonstrated remarkable success in the management of gastroenteropancreatic neuroendocrine tumors and has also been suggested to treat MTC. However, evidence on its effectiveness and long-term outcome for this indication is still limited. The objective of this study was to assess the safety and efficacy of PRRT in patients with advanced, progressive MTC and to determine survival. Potential predictors of survival were also evaluated. METHODS: From September 2003 to June 2019, 28 patients (15 men and 13 women; mean age, 49 ± 14 years) with progressive, somatostatin receptor-positive advanced MTC received PRRT with 177Lu- or 90Y-labeled somatostatin analogs at Zentralklinik Bad Berka, Germany. Toxicity was graded according to Common Terminology Criteria for Adverse Events version 5.0. Treatment response was evaluated according to RECIST (Response Evaluation Criteria in Solid Tumors) 1.1, as well as molecular imaging criteria (European Organisation for Research and Treatment of Cancer). Kaplan-Meier analysis was used to calculate progression-free survival (PFS) and overall survival (OS), defined from the start of PRRT. Univariate and multivariate Cox regression analyses were performed to identify parameters associated with PFS and OS. RESULTS: Seventy-seven cycles of PRRT were administered (mean cumulative administered activity, 16.0 ± 7.8 GBq). No acute or long-term grade 3/4 toxicity was recorded with a follow-up of 3 to 140 months, except for 1 patient (4%) who suffered from grade 3 anemia (possibly related to disease progression). According to the RECIST criteria, the disease control rate after 3 to 4 months of PRRT was 56% (partial remission, 12%; stable disease, 44%). The disease control rate (72%) was higher by molecular response evaluation. Median OS and PFS were 63.7 and 10.1 months, respectively. The annual OS rates were 84% at 1 year, 65% at 3 years, 57% at 5 years, and 18% at 10 years. The annual PFS rates were 42% at 1 year, 21% at 2 years, and 13% at 5 years. Patients with bone metastases had poorer OS and PFS than those without metastases (median OS, 58.7 vs 92.3 months [P = 0.035; hazard ratio, 2.7; 95% confidence interval, 0.92-7.84]; median PFS, 8.5 vs 12.8 months [P = 0.592; hazard ratio, 1.2; 95% confidence interval, 0.56-2.76]). CONCLUSIONS: Peptide receptor radionuclide therapy was well tolerated and effective in patients with advanced, aggressive MTC. Bone metastasis was an independent adverse prognostic factor for OS.

Salivary Gland Toxicity of PSMA-Targeted Radioligand Therapy with 177Lu-PSMA and Combined 225Ac- and 177Lu-Labeled PSMA Ligands (TANDEM-PRLT) in Advanced Prostate Cancer: A Single-Center Systematic Investigation.

Purpose: PSMA-targeted radioligand therapy (PRLT) is a promising treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). However, a high uptake of the radiopharmaceutical in the salivary glands (SG) can lead to xerostomia and becomes dose-limiting for 225Ac-PSMA-617. This study investigated the sialotoxicity of 177Lu-PSMA-I&T/-617 monotherapy and co-administered 225Ac-PSMA-617 and 177Lu-PSMA-617 (Tandem-PPRLT). Methods: Three patient cohorts, that had undergone 177Lu-PSMA-I&T/-617 monotherapy or Tandem-PRLT, were retrospectively analyzed. In a short-term cohort (91 patients), a xerostomia assessment (CTCAE v.5.0), a standardized questionnaire (sXI), salivary gland scintigraphy (SGS), and SG SUVmax and the metabolic volume (MV) on 68Ga-PSMA-11-PET/CT were obtained before and after two cycles of 177Lu-PSMA-I&T/-617. In a long-term cohort, 40 patients were similarly examined. In a Tandem cohort, the same protocol was applied to 18 patients after one cycle of Tandem-PRLT. Results: Grade 1 xerostomia in the short-term follow-up was observed in 22 (24.2%) patients with a worsening of sXI from 7 to 8 at (p < 0.05). In the long-term cohort, xerostomia grades 1 to 2 occurred in 16 (40%) patients. SGS showed no significant changes, but there was a decline of the MV of all SGs. After Tandem-PRLT, 12/18 (66.7%) patients reported xerostomia grades 1 to 2, and the sXI significantly worsened from 9.5 to 14.0 (p = 0.005), with a significant reduction in the excretion fraction (EF) and MV of all SGs. Conclusion: 177Lu-PSMA-I&T/-617 causes only minor SG toxicity, while one cycle of Tandem-PRLT results in a significant SG impairment. This standardized protocol may help to objectify and quantify SG dysfunction.

Feasibility, Biodistribution, and Preliminary Dosimetry in Peptide-Targeted Radionuclide Therapy of Diverse Adenocarcinomas Using 177Lu-FAP-2286: First-in-Humans Results.

Fibroblast activation protein (FAP) is a promising target for diagnosis and therapy of numerous malignant tumors. FAP-2286 is the conjugate of a FAP-binding peptide, which can be labeled with radionuclides for theranostic applications. We present the first-in-humans results using 177Lu-FAP-2286 for peptide-targeted radionuclide therapy (PTRT). Methods: PTRT using 177Lu-FAP-2286 was performed on 11 patients with advanced adenocarcinomas of the pancreas, breast, rectum, or ovary after prior confirmation of uptake on 68Ga-FAP-2286 or 68Ga-FAPI-04 PET/CT. Results: Administration of 177Lu-FAP-2286 (5.8 ± 2.0 GBq; range, 2.4-9.9 GBq) was well tolerated, with no adverse symptoms or clinically detectable pharmacologic effects being noticed or reported in any of the patients. The whole-body effective dose was 0.07 ± 0.02 Gy/GBq (range, 0.04-0.1 Gy/GBq). The mean absorbed doses for kidneys and red marrow were 1.0 ± 0.6 Gy/GBq (range, 0.4-2.0 Gy/GBq) and 0.05 ± 0.02 Gy/GBq (range, 0.03-0.09 Gy/GBq), respectively. Significant uptake and long tumor retention of 177Lu-FAP-2286 resulted in high absorbed tumor doses, such as 3.0 ± 2.7 Gy/GBq (range, 0.5-10.6 Gy/GBq) in bone metastases. No grade 4 adverse events were observed. Grade 3 events occurred in 3 patients-1 with pancytopenia, 1 with leukocytopenia, and 1 with pain flare-up; 3 patients reported a pain response. Conclusion:177Lu-FAP-2286 PTRT, applied in a broad spectrum of cancers, was relatively well tolerated, with acceptable side effects, and demonstrated long retention of the radiopeptide. Prospective clinical studies are warranted.

Prostate-Specific Membrane Antigen Radioligand Therapy Using 177Lu-PSMA I&T and 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer: Comparison of Safety, Biodistribution, and Dosimetry.

The objective of this study was to determine the safety, kinetics, and dosimetry of the 177Lu-labeled prostate-specific membrane antigen (PSMA) small molecules 177Lu-PSMA I&T and 177Lu-PSMA-617 in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing PSMA radioligand therapy (PRLT). Methods: In total, 138 patients (mean age, 70 ± 9 y; age range, 46-90 y) with progressive mCRPC and PSMA expression verified by 68Ga-PSMA-11 PET/CT underwent PRLT. Fifty-one patients received 6.1 ± 1.0 GBq (range, 3.4-7.6 GBq) of 177Lu-PSMA I&T, and 87 patients received 6.5 ± 1.1 GBq (range, 3.5-9.0 GBq) of 177Lu-PSMA-617. Dosimetry was performed on all patients using an identical protocol. The mean absorbed doses were estimated with OLINDA software (MIRD Scheme). Treatment-related adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 5.0, of the National Cancer Institute. Results: The whole-body half-lives were shorter for 177Lu-PSMA I&T (35 h) than for 177Lu-PSMA-617 (42 h). The mean whole-body dose of 177Lu-PSMA-617 was higher than that of 177Lu-PSMA I&T (0.04 vs. 0.03 Gy/GBq, P < 0.00001). Despite the longer half-life of 177Lu-PSMA-617, the renal dose was lower for 177Lu-PSMA-617 than for 177Lu-PSMA I&T (0.77 vs. 0.92 Gy/GBq, P = 0.0015). Both PSMA small molecules demonstrated a comparable dose to the parotid glands (0.5 Gy/GBq, P = 0.27). Among all normal organs, the lacrimal glands exhibited the highest mean absorbed doses, 5.1 and 3.7 Gy/GBq, for 177Lu-PSMA-617 and 177Lu-PSMA I&T, respectively. All tumor metastases exhibited a higher initial uptake when using 177Lu-PSMA I&T than when using 177Lu-PSMA-617, as well as a shorter tumor half-life (P < 0.00001). The mean absorbed tumor doses were comparable for both 177Lu-PSMA I&T and 177Lu-PSMA-617 (5.8 vs. 5.9 Gy/GBq, P = 0.96). All patients tolerated the therapy without any acute adverse effects. After 177Lu-PSMA-617 and 177Lu-PSMA I&T, there was a small, statistically significant reduction in hemoglobin, leukocyte counts, and platelet counts that did not need any clinical intervention. No nephrotoxicity was observed after either 177Lu-PSMA I&T or 177Lu-PSMA-617 PRLT. Conclusion: Both 177Lu-PSMA I&T and 177Lu-PSMA-617 PRLT demonstrated favorable safety in mCRPC patients. The highest absorbed doses among healthy organs were in the lacrimal and parotid glands-not, however, resulting in any significant clinical sequel. 177Lu-PSMA-617 demonstrated a higher absorbed dose to the whole-body and lacrimal glands but a lower renal dose than did 177Lu-PSMA I&T. The mean absorbed tumor doses were comparable for both 177Lu-PSMA I&T and 177Lu-PSMA-617. There was a large interpatient variability in the dosimetry parameters. Therefore, individual patient-based dosimetry seems favorable for personalized PRLT.

225Ac-DOTATOC-Targeted Somatostatin Receptor α-Therapy in a Patient With Metastatic Neuroendocrine Tumor of the Thymus, Refractory to ß-Radiation.

ABSTRACT: Somatostatin receptor-targeted α-therapy using α-emitter 225Ac-labeled somatostatin analogs has been suggested as a treatment option in advanced metastatic neuroendocrine tumors (NETs) failing treatment with ß-emitters, such as 177Lu or 90Y. Thymus NETs are rare and usually more aggressive than other neuroendocrine tumor entities. We present here a case with ß-radiation refractory metastatic thymus NET, who demonstrated an excellent therapy response (molecular and morphological remission, as well as significantly improved clinical symptoms) after 225Ac-DOTATOC-targeted α-therapy, without any adverse effects during the treatment or in the follow-up period.

First-in-Humans Application of 161Tb: A Feasibility Study Using 161Tb-DOTATOC.

161Tb has decay properties similar to those of 177Lu but, additionally, emits a substantial number of conversion and Auger electrons. The aim of this study was to apply 161Tb in a clinical setting and to investigate the feasibility of visualizing the physiologic and tumor biodistributions of 161Tb-DOTATOC. Methods:161Tb was shipped from Paul Scherrer Institute, Villigen-PSI, Switzerland, to Zentralklinik Bad Berka, Bad Berka, Germany, where it was used for the radiolabeling of DOTATOC. In 2 separate studies, 596 and 1,300 MBq of 161Tb-DOTATOC were administered to a 35-y-old male patient with a metastatic, well-differentiated, nonfunctional malignant paraganglioma and a 70-y-old male patient with a metastatic, functional neuroendocrine neoplasm of the pancreatic tail, respectively. Whole-body planar γ-scintigraphy images were acquired over a period of several days for dosimetry calculations. SPECT/CT images were reconstructed using a recently established protocol and visually analyzed. Patients were observed for adverse events after the application of 161Tb-DOTATOC. Results: The radiolabeling of DOTATOC with 161Tb was readily achieved with a high radiochemical purity suitable for patient application. Planar images and dosimetry provided the expected time-dependent biodistribution of 161Tb-DOTATOC in the liver, kidneys, spleen, and urinary bladder. SPECT/CT images were of high quality and visualized even small metastases in bones and liver. The application of 161Tb-DOTATOC was well tolerated, and no related adverse events were reported. Conclusion: This study demonstrated the feasibility of imaging even small metastases after the injection of relatively low activities of 161Tb-DOTATOC using γ-scintigraphy and SPECT/CT. On the basis of this essential first step in translating 161Tb to clinics, further efforts will be directed toward the application of 161Tb for therapeutic purposes.

Prior therapies as prognostic factors of overall survival in metastatic castration-resistant prostate cancer patients treated with [177Lu]Lu-PSMA-617. A WARMTH multicenter study (the 617 trial).

INTRODUCTION: The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [177Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the "617 trial") to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with 177Lu-PSMA-617. MATERIALS AND METHODS: The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [177Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated. RESULTS: The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS. CONCLUSION: In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [177Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0-1 is associated with a longer OS.

Prior Resection of the Primary Tumor Prolongs Survival After Peptide Receptor Radionuclide Therapy of Advanced Neuroendocrine Neoplasms.

OBJECTIVE: The aim of the study was to compare impact on survival after resection of primary tumors (PTs) after peptide receptor radionuclide therapy (PRRT). BACKGROUND: PRRT is a highly effective therapeutic option to treat locally advanced or metastatic neuroendocrine neoplasms (NENs). METHODS: We retrospectively analyzed the data of 889 patients with advanced NEN (G1-G3, stage IV) treated with at least 1 cycle of PRRT. In 486 of 889 patients (55%, group 1), PT had been removed before PRRT. Group 2 constituted 403 patients (45%) with no prior PT resection. Progression-free survival (PFS) and overall survival (OS) was determined by 68Ga SSTR-PET/CT in all patients applying RECIST and EORTC. RESULTS: Most patients had their PT in pancreas (n = 335; 38%) and small intestine (n = 284; 32%). Both groups received a mean of 4 cycles of PRRT (P = 0.835) with a mean cumulative administered radioactivity of 21.6 ±â€Š11.7 versus 22.2 ±â€Š11.2 GBq (P = 0.407). Median OS in group 1 was 134.0 months [confidence interval (CI): 118-147], whereas OS in group 2 was 67.0 months (CI: 60-80; hazard ratio 2.79); P < 0.001. Likewise, the median progression-free survival after first PRRT was longer in group 1 with 18.0 (CI: 15-20) months as compared to group 2 with 14.0 (CI: 15-18; hazard ratio 1.21) months; P = 0.012. CONCLUSIONS: A previous resection of the PT before PRRT provides a significant survival benefit in patients with NENs stage IV.

Metastatic extent predicts survival as patients with metastatic castration-resistant prostate cancer are treated with 177Lu-PSMA radioligand therapy.

PSMA based radioligand is a new investigational drug for treatment of metastatic multidrug-resistant and castration-resistant prostate cancer. Prognostic factors point to above and below average overall survival (OS) after the treatment. Kessel et al. [Theranostics 2019;9:4841-8] reported for the first time that two sites of visceral metastases, lungs and liver, differed in impact on OS after treatment with 177Lu PSMA 617. Treatment with established drugs showed the same trend. The difference in OS between the sites is independent of the type of treatment and can reflect changes in tumor biology during the progression of metastatic prostate cancer.

177Lu-DOTATOC Peptide Receptor Radionuclide Therapy in a Patient With Neuroendocrine Breast Carcinoma and Breast Invasive Ductal Carcinoma.

Radiolabeled somatostatin analogs for somatostatin receptor (SSTR)-targeted imaging and peptide receptor radionuclide therapy (PRRT) have demonstrated remarkable success in the management of SSTR-expressing neuroendocrine neoplasms. Primary neuroendocrine breast carcinoma is rare. Heterogeneous SSTR overexpression has also been documented in breast cancer, in both human breast cancer specimens and clinical studies. We report here a case of a 69-year-old woman who had both breast invasive ductal carcinoma and primary large-cell neuroendocrine breast carcinoma (Ki-67 proliferation index of 20%), with disseminated bone and lymph node metastases, demonstrating exceptional tracer uptake on Ga-DOTATOC PET/CT, and remarkably partial remission after Lu-DOTATOC PRRT.

Prognostic Value of 18F-FDG PET/CT in a Large Cohort of Patients with Advanced Metastatic Neuroendocrine Neoplasms Treated with Peptide Receptor Radionuclide Therapy.

The objective of this retrospective study was to determine the role of 18F-FDG PET/CT in a large cohort of 495 patients with metastatic neuroendocrine neoplasms (NENs) who were treated with peptide receptor radionuclide therapy (PRRT) with a long-term follow-up. Methods: The 495 patients were treated with 177Lu- or 90Y-DOTATOC/DOTATATE PRRT between February 2002 and July 2018. All subjects received both 68Ga-DOTATOC/TATE/NOC and 18F-FDG PET/CT before treatment and were followed 3-189 mo. Kaplan-Meier analysis, log-rank testing (Mantel-Cox), and Cox regression analysis were performed for overall survival (OS) and progression-free survival (PFS). Results: One hundred ninety-nine patients (40.2%) presented with pancreatic NENs, 49 with cancer of unknown primary, and 139 with midgut NENs, whereas the primary tumor was present in the rectum in 20, in the lung in 38, in the stomach in 8, and in other locations in 42. 18F-FDG PET/CT was positive in 382 (77.2%) patients and negative in 113 (22.8%) before PRRT, whereas 100% were 68Ga-DOTATOC/TATE/NOC-positive. For all patients, the median PFS and OS, defined from the start of PRRT, were 19.6 mo and 58.7 mo, respectively. Positive 18F-FDG results predicted shorter PFS (18.5 mo vs. 24.1 mo; P = 0.0015) and OS (53.2 mo vs. 83.1 mo; P < 0.001) than negative 18F-FDG results. Among the cases of pancreatic NENs, the median OS was 52.8 mo in 18F-FDG-positive subjects and 114.3 mo in 18F-FDG-negative subjects (P = 0.0006). For all patients positive for 18F-FDG uptake, and a ratio of more than 2 for the highest SUVmax on 68Ga-somatostatin receptor (SSTR) PET to the most 18F-FDG-avid tumor lesions, the median OS was 53.0 mo, compared with 43.4 mo in those patients with a ratio of less than 2 (P = 0.030). For patients with no 18F-FDG uptake (complete mismatch imaging pattern), the median OS was 108.3 mo versus 76.9 mo for an SUVmax of more than 15.0 and an SUVmax of 15.0 or less on 68Ga-SSTR PET/CT, respectively. Conclusion: The presence of positive lesions on 18F-FDG PET is an independent prognostic factor in patients with NENs treated with PRRT. Metabolic imaging with 18F-FDG PET/CT complements the molecular imaging aspect of 68Ga-SSTR PET/CT for the prognosis of survival after PRRT. High SSTR expression combined with negative 18F-FDG PET/CT results is associated with the most favorable long-term prognosis.

Successful Intra-arterial Peptide Receptor Radionuclide Therapy of DOTATOC-Negative High-Grade Liver Metastases of a Pancreatic Neuroendocrine Neoplasm Using 177Lu-DOTA-LM3: A Somatostatin Receptor Antagonist.

Radiolabeled somatostatin receptor (SSTR) antagonists have shown promise for imaging neuroendocrine neoplasms and the superiority to SSTR agonists, with lower liver background especially for the sensitive detection of liver metastases, higher tumor-to-background ratio, and favorable pharmacokinetics. The clinical data of radiolabeled SSTR antagonists for therapy are still limited. We report our experience treating a young patient with DOTATOC-negative high-grade liver metastases of a pancreatic neuroendocrine neoplasm who underwent intra-arterial peptide receptor radionuclide therapy using SSTR antagonist Lu-DOTA-LM3, demonstrating an excellent response, nearly complete remission according to molecular imaging criteria and morphological partial remission, without any significant toxicity.

Peptide Receptor Radionuclide Therapy Using 225Ac-DOTATOC Achieves Partial Remission in a Patient With Progressive Neuroendocrine Liver Metastases After Repeated ß-Emitter Peptide Receptor Radionuclide Therapy.

We present here a case with ß-radiation-refractory metastatic neuroendocrine tumors, who demonstrated an excellent therapy response after 1 cycle of Ac-DOTATOC, without any significant adverse effects even after 10 cycles of ß-emitter peptide receptor radionuclide therapy followed by α-peptide receptor radionuclide therapy.

Semiquantitative Parameters in PSMA-Targeted PET Imaging with [18F]DCFPyL: Intrapatient and Interpatient Variability of Normal Organ Uptake.

PURPOSE: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has impacted the management of patients with prostate cancer (PCa) in many parts of the world. PSMA-targeted endoradiotherapies are also being increasingly utilized and for these applications, the radiopharmaceutical distribution in normal organs is particularly important because it may limit the dose that can be delivered to tumors. In this study, we measured both interpatient and intrapatient variability of [18F]DCFPyL uptake in the most relevant normal organs. PROCEDURES: Baseline and 6-month follow-up PSMA-targeted [18F]DCFPyL PET/computed tomography (CT) scans from 39 patients with PCa were reviewed. Volumes of interest were manually drawn using the best visual approximation of the organ edge for both lacrimal glands, all four major salivary glands, the liver, the spleen, and both kidneys for all patients. The average SUVmean, the COVs, and intraclass correlation coefficients (ICCs) across scans were calculated. Bland-Altman analyses were performed for all organs to derive repeatability coefficients (RCs). RESULTS: The liver demonstrated the lowest interpatient variability (13.0 and 16.6 % at baseline and follow-up, respectively), while the spleen demonstrated the largest interpatient variability (44.6 and 51.0 % at baseline and follow-up, respectively). The lowest intrapatient variability was found in the spleen (ICC 0.86) while the highest intrapatient variability was in the kidneys (ICCs 0.40-0.50). Bland-Altman analyses showed 95 % repeatability coefficients for mean uptake > 40 % for multiple organs and were highest for the lacrimal glands, kidneys, and spleen. CONCLUSIONS: Normal organs demonstrate significant variability in uptake of the PSMA-targeted radiotracer [18F]DCFPyL. Depending on the organ, different contributions of interpatient and intrapatient factors affect the intrinsic variability. The RCs also vary significantly among the different organs were highest for the lacrimal glands, kidneys, and spleen. These findings may have important implications for the design of clinical protocols and personalized dosimetry for PSMA-targeted endoradiotherapies.

Complete Regression of Lung Metastases in a Patient With Metastatic Castration-Resistant Prostate Cancer Using 177Lu-PSMA Radioligand Therapy.

Patients with metastatic castration-resistant prostate cancer (mCRPC) and visceral (liver or lung) metastases have a poor prognosis and worse outcomes than those with bone disease with or without lymph nodes involvement. The high prostate-specific membrane antigen expression in prostate cancer metastases makes it a promising approach for targeted radionuclide therapy of prostate cancer. Lutetium-177 (Lu)-labeled prostate-specific membrane antigen radioligand therapy (Lu-PRLT) has demonstrated encouraging efficacy in mCRPC. We report here an mCRPC patient with lung, lymph nodes, and extensive bone metastases, who underwent Lu-PRLT and had excellent response to the treatment and complete regression of lung metastases after Lu-PRLT.

Twelve-Year Survival of a Patient With Lymph Node, Pulmonary, Bone, Cardiac and Intraspinal Metastases of a Rectal Neuroendocrine Neoplasm Treated With Peptide Receptor Radionuclide Therapy-The Value of Salvage Peptide Receptor Radionuclide Therapy.

We report here the 12-year survival after the first peptide receptor radionuclide therapy (PRRT) of a patient with metastatic rectal neuroendocrine neoplasms, who received 7 cycles of PRRT with Lu/Y-DOTATATE/DOTATOC in 4 treatment phases. The patient demonstrated excellent response to each cycle of treatment, without any adverse effect even after repeated PRRT cycles. Most recently, immunohistochemistry revealed a G3 neuroendocrine neoplasm and intraspinal metastasis were successfully resected by neurosurgical intervention. This case nicely demonstrates that several "salvage" PRRTs can be given over many years leading to repetitive benefit for the patient and saving patients of possible toxicity of alternative treatments.

Ectopic Corticotropin-Releasing Hormone-Secreting Pancreatic Neuroendocrine Tumor: Excellent Response of Liver Metastases to Peptide Receptor Radionuclide Therapy as Demonstrated by 68Ga-DOTATOC and 18F-FDG PET/CT Imaging.

Ectopic Cushing syndrome secondary to corticotropin releasing hormone (CRH)-secreting tumors or CRH and adrenocorticotropin hormone cosecreting tumors is extremely rare. We report here the case of a 54-year-old man who experienced CRH-secreting pancreatic neuroendocrine tumor causing Cushing syndrome, initially detected by SSTR (somatostatin receptor) scintigraphy, then significantly progressed with multiple liver metastases, demonstrating significantly increased SSTR expression on Ga-DOTATOC PET/CT and a "mismatch" imaging pattern on F-FDG PET/CT. The patient underwent peptide receptor radionuclide therapy with Lu/Y-DOTATOC and demonstrated excellent response to the treatment.

Metastatic Nasopharyngeal Carcinoma Treated With Intraarterial Combined With Intravenous Peptide Receptor Radionuclide Therapy.

Nasopharyngeal carcinoma may express somatostatin receptors (SSTR). We present a case with metastatic nasopharyngeal carcinoma in the liver, bone, and lymph nodes. The patient was in progression after chemotherapy, external beam radiation therapy (ERBT), atezolizumab, and cetuximab. Due to strong SSTR expression of the metastases, PRRT was applied. After 3 cycles of intravenous Lu-DOTATOC and 1 cycle of intraarterial Y-DOTATOC therapy, the hepatic and bone metastases showed excellent response after PRRT. No nephrotoxicity or myelotoxicity was observed.