TY - JOUR A1 - Aster, Hans-Christoph A1 - Romanos, Marcel A1 - Walitza, Susanne A1 - Gerlach, Manfred A1 - Mühlberger, Andreas A1 - Rizzo, Albert A1 - Andreatta, Marta A1 - Hasenauer, Natalie A1 - Hartrampf, Philipp E. A1 - Nerlich, Kai A1 - Reiners, Christoph A1 - Lorenz, Reinhard A1 - Buck, Andreas K. A1 - Deserno, Lorenz T1 - Responsivity of the striatal dopamine system to methylphenidate — A within-subject I-123-β-CIT-SPECT study in male children and adolescents with attention-deficit/hyperactivity disorder JF - Frontiers in Psychiatry N2 - Background: Methylphenidate (MPH) is the first-line pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD). MPH binds to the dopamine (DA) transporter (DAT), which has high density in the striatum. Assessments of the striatal dopamine transporter by single positron emission computed tomography (SPECT) in childhood and adolescent patients are rare but can provide insight on how the effects of MPH affect DAT availability. The aim of our within-subject study was to investigate the effect of MPH on DAT availability and how responsivity to MPH in DAT availability is linked to clinical symptoms and cognitive functioning. Methods Thirteen adolescent male patients (9–16 years) with a diagnosis of ADHD according to the DSM-IV and long-term stimulant medication (for at least 6 months) with MPH were assessed twice within 7 days using SPECT after application of I-123-β-CIT to examine DAT binding potential (DAT BP). SPECT measures took place in an on- and off-MPH status balanced for order across participants. A virtual reality continuous performance test was performed at each time point. Further clinical symptoms were assessed for baseline off-MPH. Results On-MPH status was associated with a highly significant change (−29.9%) of striatal DAT BP as compared to off-MPH (t = −4.12, p = 0.002). A more pronounced change in striatal DAT BP was associated with higher off-MPH attentional and externalizing symptom ratings (Pearson r = 0.68, p = 0.01). Striatal DAT BP off-MPH, but not on-MPH, was associated with higher symptom ratings (Pearson r = 0.56, p = 0.04). Conclusion Our findings corroborate previous reports from mainly adult samples that MPH changes striatal DAT BP availability and suggest higher off-MPH DAT BP, likely reflecting low baseline DA levels, as a marker of symptom severity. KW - methylphenidate KW - attention deficit/hyperactivity disorder (ADHD) KW - striatum KW - single photon emission computed tomography (SPECT) KW - responsivity KW - caudate nucleus KW - dopamine transporter (DAT) Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270862 SN - 1664-0640 VL - 13 ER - TY - JOUR A1 - Hartrampf, Philipp E. A1 - Krebs, Markus A1 - Peter, Lea A1 - Heinrich, Marieke A1 - Ruffing, Julia A1 - Kalogirou, Charis A1 - Weinke, Maximilian A1 - Brumberg, Joachim A1 - Kübler, Hubert A1 - Buck, Andreas K. A1 - Werner, Rudolf A. A1 - Seitz, Anna Katharina T1 - Reduced segmentation of lesions is comparable to whole-body segmentation for response assessment by PSMA PET/CT: initial experience with the keyhole approach JF - Biology N2 - Simple Summary The calculation of PSMA-positive tumor volume (PSMA-TV) of the whole body from PSMA PET scans for response evaluation remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative tumor lesions. Changes in the whole-body PSMA-TV of 65 patients were comparable to the changes in PSMA-TV after including only the ten largest lesions. Moreover, changes in PSMA-TV correlated well with changes in PSA levels, as did the changes in PSMA-TV with the reduced number of lesions. We conclude that a response assessment using PSMA-TV with a reduced number of lesions is feasible and could lead to a simplified process for evaluating PSMA PET/CT. Abstract (1) Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-derived parameters, such as the commonly used standardized uptake value (SUV) and PSMA-positive tumor volume (PSMA-TV), have been proposed for response assessment in metastatic prostate cancer (PCa) patients. However, the calculation of whole-body PSMA-TV remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative lesions. (2) Methods: Sixty-five patients classified into different disease stages were assessed by PSMA PET/CT for staging and restaging after therapy. Whole-body PSMA-TV and whole-body SUV\(_{max}\) were calculated. We then repeated this calculation only including the five or ten hottest or largest lesions. The corresponding serum levels of prostate-specific antigen (PSA) were also determined. The derived delta between baseline and follow-up values provided the following parameters: ΔSUV\(_{maxall}\), ΔSUV\(_{max10}\), ΔSUV\(_{max5}\), ΔPSMA-TV\(_{all}\), ΔPSMA-TV\(_{10}\), ΔPSMA-TV\(_{5}\), ΔPSA. Finally, we compared the findings from our whole-body segmentation with the results from our keyhole approach (focusing on a limited number of lesions) and correlated all values with the biochemical response (ΔPSA). (3) Results: Among patients with metastatic hormone-sensitive PCa (mHSPC), none showed a relevant deviation for ΔSUV\(_{max10}\)/ΔSUV\(_{max5}\) or ΔPSMA-TV\(_{10}\)/ΔPSMA-TV\(_{5}\) compared to ΔSUV\(_{maxall}\) and ΔPSMA-TV\(_{all}\). For patients treated with taxanes, up to 6/21 (28.6%) showed clinically relevant deviations between ΔSUV\(_{maxall}\) and ΔSUV\(_{max10}\) or ΔSUV\(_{max5}\), but only up to 2/21 (9.5%) patients showed clinically relevant deviations between ΔPSMA-TV\(_{all}\) and ΔPSMA-TV\(_{10}\) or ΔPSMA-TV\(_{5}\). For patients treated with radioligand therapy (RLT), up to 5/28 (17.9%) showed clinically relevant deviations between ΔSUV\(_{maxall}\) and ΔSUV\(_{max10}\) or ΔSUV\(_{max5}\), but only 1/28 (3.6%) patients showed clinically relevant deviations between ΔPSMA-TV\(_{all}\) and ΔPSMA-TV\(_{10}\) or ΔPSMA-TV\(_{5}\). The highest correlations with ΔPSA were found for ΔPSMA-TV\(_{all}\) (r ≥ 0.59, p ≤ 0.01), followed by ΔPSMA-TV\(_{10}\) (r ≥ 0.57, p ≤ 0.01) and ΔPSMA-TV\(_{5}\) (r ≥ 0.53, p ≤ 0.02) in all cohorts. ΔPSA only correlated with ΔSUV\(_{maxall}\) (r = 0.60, p = 0.02) and with ΔSUV\(_{max10}\) (r = 0.53, p = 0.03) in the mHSPC cohort, as well as with ΔSUV\(_{maxall}\) (r = 0.51, p = 0.01) in the RLT cohort. (4) Conclusion: Response assessment using PSMA-TV with a reduced number of lesions is feasible, and may allow for a simplified evaluation process for PSMA PET/CT. KW - PET/CT KW - PSMA-TV KW - SUV KW - prostate cancer KW - taxane KW - radioligand therapy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-271191 SN - 2079-7737 VL - 11 IS - 5 ER - TY - JOUR A1 - Hartrampf, Philipp E. A1 - Petritsch, Bernhard A1 - Buck, Andreas K. A1 - Serfling, Sebastian E. T1 - Pitfalls in PSMA-PET/CT: Intensive bone-marrow uptake in a case with polycythaemia vera JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - No abstract available. KW - bone-marrow Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235608 SN - 1619-7070 VL - 48 ER - TY - JOUR A1 - Heinze, Britta A1 - Schirbel, Andreas A1 - Nannen, Lukas A1 - Michelmann, David A1 - Hartrampf, Philipp E. A1 - Bluemel, Christina A1 - Schneider, Magdalena A1 - Herrmann, Ken A1 - Haenscheid, Heribert A1 - Fassnacht, Martin A1 - Buck, Andreas K. A1 - Hahner, Stefanie T1 - Novel CYP11B-ligand [\(^{123/131}\)I]IMAZA as promising theranostic tool for adrenocortical tumors: comprehensive preclinical characterization and first clinical experience JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - Purpose Adrenal tumors represent a diagnostic and therapeutic challenge. Promising results have been obtained through targeting the cytochrome P450 enzymes CYP11B1 and CYP11B2 for molecular imaging, and [\(^{123/131}\)I]iodometomidate ([\(^{123/131}\)I]IMTO) has even been successfully introduced as a theranostic agent. As this radiopharmaceutical shows rapid metabolic inactivation, we aimed at developing new improved tracers. Methods Several IMTO derivatives were newly designed by replacing the unstable methyl ester by different carboxylic esters or amides. The inhibition of aldosterone and cortisol synthesis was tested in different adrenocortical cell lines. The corresponding radiolabeled compounds were assessed regarding their stability, in vitro cell uptake, in vivo biodistribution in mice, and their binding specificity to cryosections of human adrenocortical and non-adrenocortical tissue. Furthermore, a first investigation was performed in patients with known metastatic adrenal cancer using both [\(^{123}\)I]IMTO and the most promising compound (R)-1-[1-(4-[\(^{123/}\)I]iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinylamide ([\(^{123}\)I]IMAZA) for scintigraphy. Subsequently, a first endoradiotherapy with [\(^{131}\)I]IMAZA in one of these patients was performed. Results We identified three analogues to IMTO with high-affinity binding to the target enzymes and comparable or higher metabolic stability and very high and specific accumulation in adrenocortical cells in vitro and in vivo. Labeled IMAZA exhibited superior pharmacokinetic and imaging properties compared to IMTO in mice and 3 patients, too. An endoradiotherapy with [\(^{131}\)I]IMAZA induced a 21-month progression-free interval in a patient with rapidly progressing ACC prior this therapy. Conclusion We developed the new radiopharmaceutical [\(^{123/131}\)I]IMAZA with superior properties compared to the reference compound IMTO and promising first experiences in humans. KW - CYP11B enzymes KW - adrenal incidentaloma KW - adrenocortical carcinoma Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265606 SN - 1619-7089 VL - 49 IS - 1 ER - TY - JOUR A1 - Hartrampf, Philipp E. A1 - Heinrich, Marieke A1 - Seitz, Anna Katharina A1 - Brumberg, Joachim A1 - Sokolakis, Ioannis A1 - Kalogirou, Charis A1 - Schirbel, Andreas A1 - Kübler, Hubert A1 - Buck, Andreas K. A1 - Lapa, Constantin A1 - Krebs, Markus T1 - Metabolic Tumour Volume from PSMA PET/CT Scans of Prostate Cancer Patients during Chemotherapy — Do Different Software Solutions Deliver Comparable Results? JF - Journal of Clinical Medicine N2 - (1) Background: Prostate-specific membrane antigen (PSMA)-derived tumour volume (PSMA-TV) and total lesion PSMA (TL-PSMA) from PSMA PET/CT scans are promising biomarkers for assessing treatment response in prostate cancer (PCa). Currently, it is unclear whether different software tools for assessing PSMA-TV and TL-PSMA produce comparable results. (2) Methods: \(^{68}\)Ga-PSMA PET/CT scans from n = 21 patients with castration-resistant PCa (CRPC) receiving chemotherapy were identified from our single-centre database. PSMA-TV and TL-PSMA were calculated with Syngo.via (Siemens) as well as the freely available Beth Israel plugin for FIJI (Fiji Is Just ImageJ) before and after chemotherapy. While statistical comparability was illustrated and quantified via Bland-Altman diagrams, the clinical agreement was estimated by matching PSMA-TV, TL-PSMA and relative changes of both variables during chemotherapy with changes in serum PSA (ΔPSA) and PERCIST (Positron Emission Response Criteria in Solid Tumors). (3) Results: Comparing absolute PSMA-TV and TL-PSMA as well as Bland–Altman plotting revealed a good statistical comparability of both software algorithms. For clinical agreement, classifying therapy response did not differ between PSMA-TV and TL-PSMA for both software solutions and showed highly positive correlations with BR. (4) Conclusions: due to the high levels of statistical and clinical agreement in our CRPC patient cohort undergoing taxane chemotherapy, comparing PSMA-TV and TL-PSMA determined by Syngo.via and FIJI appears feasible. KW - prostate-specific membrane antigen (PSMA) KW - metabolic tumour volume (MTV) KW - total lesion PSMA KW - biomarker KW - software KW - comparability KW - agreement Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-205893 SN - 2077-0383 VL - 9 IS - 5 ER - TY - JOUR A1 - Hartrampf, Philipp E. A1 - Bundschuh, Ralph A. A1 - Weinzierl, Franz-Xaver A1 - Serfling, Sebastian E. A1 - Kosmala, Aleksander A1 - Seitz, Anna Katharina A1 - Kübler, Hubert A1 - Buck, Andreas K. A1 - Essler, Markus A1 - Werner, Rudolf A. T1 - mCRPC patients with PSA fluctuations under radioligand therapy have comparable survival benefits relative to patients with sustained PSA decrease JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - Introduction In men with metastatic castration-resistant prostate cancer (mCRPC) scheduled for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), biochemical response is assessed based on repeated measurements of prostate-specific antigen (PSA) levels. We aimed to determine overall survival (OS) in patients experiencing sustained PSA increase, decrease, or fluctuations during therapy. Materials and methods In this bicentric study, we included 176 mCRPC patients treated with PSMA-directed RLT. PSA levels were determined using blood samples prior to the first RLT and on the admission days for the following cycles. We calculated relative changes in PSA levels compared to baseline. Kaplan–Meier curves as well as log-rank test were used to compare OS of different subgroups, including patients with sustained PSA increase, decrease, or fluctuations (defined as change after initial decrease or increase after the first cycle). Results Sixty-one out of one hundred seventy-six (34.7%) patients showed a sustained increase and 86/176 (48.8%) a sustained decrease in PSA levels. PSA fluctuations were observed in the remaining 29/176 (16.5%). In this subgroup, 22/29 experienced initial PSA decrease followed by an increase (7/29, initial increase followed by a decrease). Median OS of patients with sustained decrease in PSA levels was significantly longer when compared to patients with sustained increase of PSA levels (19 vs. 8 months; HR 0.35, 95% CI 0.22–0.56; P < 0.001). Patients with PSA fluctuations showed a significantly longer median OS compared to patients with sustained increase of PSA levels (18 vs. 8 months; HR 0.49, 95% CI 0.30–0.80; P < 0.01), but no significant difference relative to men with sustained PSA decrease (18 vs. 19 months; HR 1.4, 95% CI 0.78–2.49; P = 0.20). In addition, in men experiencing PSA fluctuations, median OS did not differ significantly between patients with initial decrease or initial increase of tumor marker levels (16 vs. 18 months; HR 1.2, 95% CI 0.38–4.05; P = 0.68). Conclusion Initial increase or decrease of PSA levels is sustained in the majority of patients undergoing RLT. Sustained PSA decrease was linked to prolonged survival and men with PSA fluctuations under treatment experienced comparable survival benefits. As such, transient tumor marker oscillations under RLT should rather not lead to treatment discontinuation, especially in the absence of radiological progression. KW - radioligand therapy KW - late response KW - flare phenomenon KW - PSA KW - prostate cancer KW - PSMA Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324562 VL - 49 IS - 13 ER - TY - JOUR A1 - Hartrampf, Philipp E. A1 - Weinzierl, Franz-Xaver A1 - Buck, Andreas K. A1 - Rowe, Steven P. A1 - Higuchi, Takahiro A1 - Seitz, Anna Katharina A1 - Kübler, Hubert A1 - Schirbel, Andreas A1 - Essler, Markus A1 - Bundschuh, Ralph A. A1 - Werner, Rudolf A. T1 - Matched-pair analysis of [\(^{177}\)Lu]Lu-PSMA I&T and [\(^{177}\)Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - Background Labelled with lutetium-177, the urea-based small molecules PSMA I&T and PSMA-617 are the two agents most frequently used for radioligand therapy (RLT) in patients with advanced metastatic castration-resistant and prostate-specific membrane antigen (PSMA) expressing prostate cancer (mCRPC). In this matched-pair analysis, we aimed to compare the toxicity and efficacy of both agents for PSMA-directed RLT. Materials and methods A total of 110 mCRPC patients from two centres were accrued, 55 individuals treated with [\(^{177}\)Lu]Lu-PSMA I&T, and a matched cohort of 55 patients treated with [\(^{177}\)Lu]Lu-PSMA-617. Matching criteria included age at the first cycle, Gleason score, prostate-specific antigen (PSA) values, and previous taxane-based chemotherapy. Using common terminology criteria for adverse events (CTCAE v. 5.0), toxicity profiles were investigated (including bone marrow and renal toxicity). Overall survival (OS) between both groups was compared. Results Toxicity assessment revealed grade III anaemia in a single patient (1.8%) for [\(^{177}\)Lu]Lu-PSMA I&T and five (9.1%) for [\(^{177}\)Lu]Lu-PSMA-617. In addition, one (1.9%) grade III thrombopenia for [\(^{177}\)Lu]Lu-PSMA-617 was recorded. Apart from that, no other grade III/IV toxicities were present. A median OS of 12 months for patients treated with [\(^{177}\)Lu]Lu-PSMA I&T did not differ significantly when compared to patients treated with [\(^{177}\)Lu]Lu-PSMA-617 (median OS, 13 months; P = 0.89). Conclusion In this matched-pair analysis of patients receiving one of the two agents most frequently applied for PSMA RLT, the rate of clinically relevant toxicities was low for both compounds. In addition, no relevant differences for OS were observed. KW - PSMA I&T KW - PSMA-617 KW - prostate-specific membrane antigen KW - prostate cancer KW - radioligand therapy KW - matched pair Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324581 VL - 49 IS - 9 ER - TY - JOUR A1 - Hänscheid, Heribert A1 - Hartrampf, Philipp E. A1 - Schirbel, Andreas A1 - Buck, Andreas K. A1 - Lapa, Constantin T1 - Intraindividual comparison of [\(^{177}\)Lu]Lu-DOTA-EB-TATE and [\(^{177}\)Lu]Lu-DOTA-TOC JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - Purpose The radiolabelled somatostatin analogue [\(^{177}\)Lu]Lu-DOTA-EB-TATE binds to albumin via Evans blue, thereby increasing the residence time in the blood and potentially allowing more therapeutic agent to be absorbed into the target tissue during peptide receptor radionuclide therapy. It was tested in selected patients whether the substance is superior to [\(^{177}\)Lu]Lu-DOTA-TOC. Methods Activity kinetics in organs and tumours after [\(^{177}\)Lu]Lu-DOTA-EB-TATE and [\(^{177}\)Lu]Lu-DOTA-TOC were compared intraindividually in five patients with progressive somatostatin receptor-positive disease scheduled for radionuclide therapy. Resuluts In comparison to [\(^{177}\)Lu]Lu-DOTA-TOC, tumour doses per administered activity were higher for [\(^{177}\)Lu]Lu-DOTA-EB-TATE in 4 of 5 patients (median ratio: 1.7; range: 0.9 to 3.9), kidney doses (median ratio: 3.2; range: 1.6 to 9.8) as well as spleen doses (median ratio: 4.7; range 1.2 to 6.2) in all patients, and liver doses in 3 of 4 evaluable patients (median ratio: 4.0; range: 0.7 to 4.9). The tumour to critical organs absorbed dose ratios were higher after [\(^{177}\)Lu]Lu-DOTA-TOC in 4 of 5 patients. Conclusions Prior to a treatment with [\(^{177}\)Lu]Lu-DOTA-EB-TATE, it should be assessed individually whether the compound is superior to established substances. KW - intraindividual comparison KW - DOTA-EB-TATE KW - somatostatin receptor KW - evans blue KW - biokinetics Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265470 SN - 1619-7089 VL - 48 IS - 8 ER - TY - JOUR A1 - Serfling, Sebastian E. A1 - Lapa, Constantin A1 - Dreher, Niklas A1 - Hartrampf, Philipp E. A1 - Rowe, Steven P. A1 - Higuchi, Takahiro A1 - Schirbel, Andreas A1 - Weich, Alexander A1 - Hahner, Stefanie A1 - Fassnacht, Martin A1 - Buck, Andreas K. A1 - Werner, Rudolf A. T1 - Impact of tumor burden on normal organ distribution in patients imaged with CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT JF - Molecular Imaging and Biology N2 - Background CXCR4-directed positron emission tomography/computed tomography (PET/CT) has been used as a diagnostic tool in patients with solid tumors. We aimed to determine a potential correlation between tumor burden and radiotracer accumulation in normal organs. Methods Ninety patients with histologically proven solid cancers underwent CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT. Volumes of interest (VOIs) were placed in normal organs (heart, liver, spleen, bone marrow, and kidneys) and tumor lesions. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were determined. For CXCR4-positive tumor burden, maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA, defined as SUV\(_{mean}\) x TV), were calculated. We used a Spearman's rank correlation coefficient (ρ) to derive correlative indices between normal organ uptake and tumor burden. Results Median SUV\(_{mean}\) in unaffected organs was 5.2 for the spleen (range, 2.44 – 10.55), 3.27 for the kidneys (range, 1.52 – 17.4), followed by bone marrow (1.76, range, 0.84 – 3.98), heart (1.66, range, 0.88 – 2.89), and liver (1.28, range, 0.73 – 2.45). No significant correlation between SUV\(_{max}\) in tumor lesions (ρ ≤ 0.189, P ≥ 0.07), TV (ρ ≥ -0.204, P ≥ 0.06) or FTA (ρ ≥ -0.142, P ≥ 0.18) with the investigated organs was found. Conclusions In patients with solid tumors imaged with [\(^{68}\)Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged. KW - CXCR4 KW - C-X-C motif chemokine receptor 4 KW - PET KW - [68Ga]PentixaFor KW - [177Lu]/[90Y]PentixaTher KW - theranostics KW - endoradiotherapy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324622 VL - 24 IS - 4 ER - TY - JOUR A1 - Hartrampf, Philipp E. A1 - Weinzierl, Franz-Xaver A1 - Serfling, Sebastian E. A1 - Pomper, Martin G. A1 - Rowe, Steven P. A1 - Higuchi, Takahiro A1 - Seitz, Anna Katharina A1 - Kübler, Hubert A1 - Buck, Andreas K. A1 - Werner, Rudolf A. T1 - Hematotoxicity and nephrotoxicity in prostate cancer patients undergoing radioligand therapy with [\(^{177}\)Lu]Lu-PSMA I&T JF - Cancers N2 - (1) Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) has shown remarkable results in patients with advanced prostate cancer. We aimed to evaluate the toxicity profile of the PSMA ligand [\(^{177}\)Lu]Lu-PSMA I&T. (2) Methods: 49 patients with metastatic, castration-resistant prostate cancer treated with at least three cycles of [\(^{177}\)Lu]Lu-PSMA I&T were evaluated. Prior to and after RLT, we compared leukocytes, hemoglobin, platelet counts, and renal functional parameters (creatinine, eGFR, n = 49; [\(^{99m}\)Tc]-MAG3-derived tubular extraction rate (TER), n = 42). Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and KDIGO Society. To identify predictive factors, we used Spearman's rank correlation coefficient. (3) Results: A substantial fraction of the patients already showed impaired renal function and reduced leukocyte counts at baseline. Under RLT, 11/49 (22%) patients presented with nephrotoxicity CTCAE I or II according to creatinine, but 33/49 (67%) according to eGFR. Only 5/42 (13%) showed reduced TER, defined as <70% of the age-adjusted mean normal values. Of all renal functional parameters, absolute changes of only 2% were recorded. CTCAE-based re-categorization was infrequent, with creatinine worsening from I to II in 2/49 (4.1%; GFR, 1/49 (2%)). Similar results were recorded for KDIGO (G2 to G3a, 1/49 (2%); G3a to G3b, 2/49 (4.1%)). After three cycles, follow-up eGFR correlated negatively with age (r = −0.40, p = 0.005) and the eGFR change with Gleason score (r = −0.35, p < 0.05) at baseline. Leukocytopenia CTCAE II occurred only in 1/49 (2%) (CTCAE I, 20/49 (41%)) and CTCAE I thrombocytopenia in 7/49 (14%), with an absolute decrease of 15.2% and 16.6% for leukocyte and platelet counts. Anemia CTCAE II occurred in 10/49 (20%) (CTCAE I, 36/49 (73%)) with a decrease in hemoglobin of 4.7%. (4) Conclusions: After PSMA-targeted therapy using [\(^{177}\)Lu]Lu-PSMA I&T, no severe (CTCAE III/IV) toxicities occurred, thereby demonstrating that serious adverse renal or hematological events are unlikely to be a frequent phenomenon with this agent. KW - PSMA KW - radioligand therapy KW - RLT KW - \(^{177}\)Lu KW - nephrotoxicity KW - hematotoxicity KW - CTCAE Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254825 SN - 2072-6694 VL - 14 IS - 3 ER -