BackgroundRadioligand therapy (RLT) with 177Lu-DKFZ-617 PSMA (Lu-PSMA) (prostate-specific membrane antigen) is a novel targeted therapy of metastatic prostate cancer. We analysed retrospectively the early side effects and the response rate in the first patients, who received a therapy with Lu-PSMA in our departments.MethodsRLT was performed in ten hormone- and/or chemo-refractory patients with distant metastases and progressive disease (mean age 73.5 years). 68Ga-PSMA HBED-CC PET/CT was performed in all patients prior to RLT. The median PSA level prior to the therapy was 298.5 ng/ml (range 5–853 ng/ml). All patients received CBC, renal and liver function tests the day before and 2 days after application (mean administered activity 5.6 GBq, range 4.1–6.1 GBq), followed by further tests every 2 weeks. All patients were contacted by telephone every week regarding side effects or any positive and negative changes.ResultsEight weeks after the therapy, seven patients (70 %) experienced a PSA decline, of whom six experienced more than 30 % and five more than 50 %. Three patients showed a progressive disease according to the PSA increase. No patient experienced any side effects immediately after injection of Lu-PSMA. Relevant hematotoxicity (grade 3 or 4) occurred 7 weeks after the administration in just one patient. The same patient showed a leucopenia grade 2. Two patients showed a disturbance of only 1 hematologic cell line, whereas one patient showed a reduction of grades 1 and 2 in leucocytes and thrombocytes, respectively. Six patients did not show any hematotoxicity during the 8 weeks after therapy. There was no relevant nephrotoxicity (grade 3 or 4).ConclusionsOur initial results indicate that RLT with Lu-PSMA is safe and seems to have low early side-effect profile. A relevant PSA decline was detected in 70 % of patients.

Radiolabeled prostate-specific membrane antigen (PSMA) ligands represent a true theranostic concept for diagnosis and therapy in patients with relapsed or metastatic prostate cancer. The aim of this study was to evaluate the response to and tolerability of a single dose of 177 Lu-PSMA-617 in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: The data of 82 consecutive patients (median age, 73 y; range, 43-87 y) with mCRPC who received a single dose of 177 Lu-PSMA-617 (mean, 5.9 ± 0.5 GBq) were retrospectively analyzed. Data were collected at baseline and 8 wk after therapy. 68 Ga-PSMA-11 PET/CT was performed on all patients to verify sufficient PSMA expression. Bone, lymph node, liver, and lung metastases were present in 99%, 65%, 17%, and 11% of the patients, respectively. Tolerability and response were evaluated using hematologic parameters, renal scintigraphy, clinical data, and the prostate-specific antigen (PSA) level at baseline and 8 wk after therapy application. Results: Six patients died, and 2 patients dropped out because they were not willing to continue therapy and follow-up. The complete dataset of 74 patients was available for analysis. Forty-seven patients (64%) showed a PSA decline, including 23 (31%) with a decline by more than 50%. Thirty-five patients (47%) had stable disease: the change in their PSA level ranged from less than a 50% decline to less than a 25% rise. Seventeen patients (23%) had progressive disease: their PSA level rose by more than 25%. There were no significant changes in hemoglobin, white blood cells, creatinine, or tubular extraction rates indicative of toxicity. There was a significant but mild decrease in platelets, but the median value was still within the reference range. Conclusion: This retrospective multicenter analysis suggests that radioligand therapy with 177 Lu-PSMA-617 is safe and well tolerated and has a considerable effect on PSA level. Therefore, it offers an additional therapeutic option for patients with mCRPC. These data may justify further prospective randomized studies to evaluate and prove the clinical benefit in terms of survival and quality of life.

Results from 50 therapies show that radioligand therapy with Lu-PSMA-617 is effective and well tolerated and seems to increase overall survival. A future randomized controlled prospective study will be necessary to confirm these results.

Treatment of (silylalkynyl)benzenes with (Me3C)2GaH afforded stable cis‐addition products, for example, (Me3C)2GaC(SiMe3)C(H)C6H5 (1), while spontaneous cis/trans rearrangement was observed for sterically less shielded gallium hydrides. The corresponding trans‐di(tert‐butyl)gallium compounds (13, 14) were obtained by the reaction of C6H6−n[C(H)C(SiMe3)GaCl2]n (11, 12) with LiCMe3. In contrast, spontaneous isomerization took place upon reaction of (Me3C)2AlH with phenyltrimethylsilylethyne. In this case the cis isomer (17) was detected only at low temperature, while the trans product (18) formed quantitatively above 0 °C. Quantum‐chemical calculations showed that the trans forms are thermodynamically favored, essentially caused by a better mesomeric interaction of the CC double bonds with the phenyl groups, a smaller steric stress in the molecules, and a short bonding contact of the coordinatively unsaturated Al or Ga atoms to CH bonds of the aromatic rings. The rotation about the CC double bonds follows a zwitterionic mechanism, and the relatively small rotational barrier is further lowered by an interaction to a Lewis acidic lithium cation.

Hydrogallation of 1,4-bis(trimethylsilylethynyl)benzene and 1,3,5-tris(trimethylsilylethynyl)benzene with dialkylgallium hydrides R2GaH (R = Et, nPr, iPr, neopentyl, tBu) afforded the corresponding addition products with intact GaR2 groups and two or three alkenyl substituents. In all products the gallium atoms attacked those carbon atoms that are attached to the trimethylsilyl groups. The expected cis arrangement of gallium and hydrogen atoms at the CC double bonds was detected only with di(tert-butyl)gallium residues. Smaller alkyl groups gave the spontaneous formation of the trans-addition products. Cis/trans isomerization is an inevitable step for the formation of effective chelating Lewis acids, and in particular the trisalkene derivatives form interesting chalice-like hollows containing three Lewis-acidic centers at their inner surfaces.