Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy is increasingly used in metastatic castration-resistant prostate cancer. We aimed to estimate the absorbed doses for normal organs and tumor lesions using 177 Lu-PSMA I&T (I&T is imaging and therapy) in patients undergoing up to 4 cycles of radioligand therapy. Results were compared with pretherapeutic Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBEDCC)] ( 68 Ga-PSMA-HBED-CC) PET. Methods: A total of 34 cycles in 18 patients were analyzed retrospectively. In 15 patients the first, in 9 the second, in 5 the third, and in 5 the fourth cycle was analyzed, respectively. Whole-body scintigraphy was performed at least between 30-120 min, 24 h, and 6-8 d after administration. Regions of interest covering the whole body, organs, and up to 4 tumor lesions were drawn. Organ and tumor masses were derived from pretherapeutic 68 Ga-PSMA-HBED-CC PET/CT. Absorbed doses for individual cycles were calculated using OLINDA/EXM. SUVs from pretherapeutic PET were compared with absorbed doses and with change of SUV. Results: The mean whole-body effective dose for all cycles was 0.06 6 0.03 Sv/GBq. The mean absorbed organ doses were 0.72 6 0.21 Gy/GBq for the kidneys; 0.12 6 0.06 Gy/GBq for the liver; and 0.55 6 0.14 Gy/GBq for the parotid, 0.64 6 0.40 Gy/ GBq for the submandibular, and 3.8 6 1.4 Gy/GBq for the lacrimal glands. Absorbed organ doses were relatively constant among the 4 different cycles. Tumor lesions received a mean absorbed dose per cycle of 3.2 6 2.6 Gy/GBq (range, 0.22-12 Gy/GBq). Doses to tumor lesions gradually decreased, with 3.5 6 2.9 Gy/GBq for the first, 3.3 6 2.5 Gy/GBq for the second, 2.7 6 2.3 Gy/GBq for the third, and 2.4 6 2.2 Gy/GBq for the fourth cycle. SUVs of pretherapeutic PET moderately correlated with absorbed dose (r 5 0.44, P , 0.001 for SUV max ; r 5 0.43, P , 0.001 for SUV mean ) and moderately correlated with the change of SUV (r 5 0.478, P , 0.001 for SUV max , and r 5 0.50, P , 0.001 for SUV mean ). Conclusion: Organ-and tumorabsorbed doses for 177 Lu-PSMA I&T are comparable to recent reports and complement these with information on an excellent correlation between the 4 therapy cycles. With the kidneys representing the critical organ, a cumulative activity of 40 GBq of 177 Lu-PSMA I&T appears to be safe and justifiable. The correlation between pretherapeutic SUV and absorbed tumor dose emphasizes the need for PSMA-ligand PET imaging for patient selection.

The aim of this work was to develop a theranostic method that allows predicting PSMA-positive tumor volume after radioligand therapy (RLT) based on a pre-therapeutic PET/CT measurement and physiologically based pharmacokinetic/dynamic (PBPK/PD) modeling at the example of RLT using Lu-labeled PSMA for imaging and therapy (PSMA I&T). A recently developed PBPK model forLu PSMA I&T RLT was extended to account for tumor (exponential) growth and reduction due to irradiation (linear quadratic model). Data of 13 patients with metastatic castration-resistant prostate cancer (mCRPC) were retrospectively analyzed. Pharmacokinetic/dynamic parameters were simultaneously fitted in a Bayesian framework to PET/CT activity concentrations, planar scintigraphy data and tumor volumes prior and post (6 weeks) therapy. The method was validated using the leave-one-out Jackknife method. The tumor volume post therapy was predicted based on pre-therapy PET/CT imaging and PBPK/PD modeling. The relative deviation of the predicted and measured tumor volume for PSMA-positive tumor cells (6 weeks post therapy) was 1±40% excluding one patient (PSA negative) from the population. The radiosensitivity for the PSA positive patients was determined to be 0.0172±0.0084 Gy-1. The proposed method is the first attempt to solely use PET/CT and modeling methods to predict the PSMA-positive tumor volume after radioligand therapy. Internal validation shows that this is feasible with an acceptable accuracy. Improvement of the method and external validation of the model is ongoing.

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Occupational rehabilitation in Germany is done in specialized centres (so-called "Phase II" centres). In the present study, long-term outcome data of 237 neurological rehabilitation patients (mean age 38.3 years) were analyzed. Most of the patients had suffered brain injuries. The examination took place some 7 years after the end of occupational rehabilitation and approximately 10 years after the injury. About 60% of patients returned to work (35% worked, 9.3% were seeking a job, 13.5% underwent training). Positive predictors for return to work were lower age and high educational level. The results from this study suggest that occupational rehabilitation is effective. Controlled and multi-centre studies should be carried out.

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Introduction: Radiohybrid prostate-specific membrane antigen (rhPSMA)-ligands allow for labelling with 18 F and radiometals for endoradiotherapy. rhPSMA-7.3 is designated as lead compound with promising preclinical data for 177 Lu-rhPSMA-7.3 indicating higher tumor uptake compared with 177 Lu-PSMA-I&T. In this retrospective analysis we compared pre-therapeutic clinical dosimetry of both PSMA-ligands.Methods: Six mCRPC patients underwent both 177 Lu-rhPSMA-7.3 and 177 Lu-PSMA-I&T pre-therapeutic dosimetry. Whole-body scintigraphy was performed at 1h, 4h, 24h, 48h and 7d post injection. Regions of interest (ROI) covering the whole body, organs, bone marrow and tumor lesions per patient were drawn. Absorbed doses for individual patients and pre-therapeutic applications were calculated using OLINDA/EXM. To facilitate comparison of both ligands we introduced the therapeutic index (TI) defined as ratio of mean pre-therapeutic doses to tumor lesions over relevant organs-at-risk.Results: Mean whole-body pre-therapeutic effective doses were 0.12±0.07 vs. 0.05±0.03 Sv/GBq and mean absorbed organ doses were e.g. 1.65±0.28 vs. 0.73±0.18 Gy/GBq for the kidneys; 0.19±0.09 vs. 0.07±0.03 Gy/GBq for the liver and 2.35±0.78 vs. 0.80±0.41 Gy/GBq for the parotid, for the bone marrow 0.67±0.62 vs. 0.30±0.27 Gy/GBq for 177 Lu-rhPSMA-7.3 vs. 177 Lu-PSMA-I&T, respectively. Tumor lesions received a mean absorbed doses of 6.44±6.44 vs. 2.64±2.24 Gy/GBq for 177 Lu-rhPSMA-7.3 vs. 177 Lu-PSMA-I&T, respectively. The mean TI(kidney) and TI(bone_marrow) were 3.7±2.2 vs. 3.6±2.2 and 15.2±10.2 vs. 15.1±10.2, for 177 Lu-rhPSMA-7.3 vs. 177 Lu-PSMA-I&T, respectively. Conclusion:Pre-therapeutic clinical dosimetry confirmed preclinical results with 2-3 times higher mean absorbed doses for tumors of 177 Lu-rhPSMA-7.3 compared to 177 Lu-PSMA-I&T. Absorbed doses to normal organs also tended to be higher for 177 Lu-rhPSMA-7.3 resulting overall in a similar average TI for both radiopharmaceuticals with considerable inter-patient variability. 177 Lu-rhPSMA-7.3 holds promise for similar therapeutic efficacy as 177 Lu-PSMA-I&T at lower amounts of injected activity simplifying radiation safety measurements (especially for large patient numbers and/or dose escalation regimes).

The so-called Würzburg Screening (WS) is recommended for assessing occupational problems among rehabilitation patients. However, it is unclear whether it can be used in neurological rehabilitation. Data of the WS as well as of a medical opinion of occupational problems (both assessed at the beginning of rehabilitation) was compared with prognoses of occupation at the end of rehabilitation. Data of 347 neurological post-acute rehabilitation patients were analyzed. Data of the WS as well as of a medical opinion of occupational problems (both assessed at the beginning of rehabilitation) was compared with prognoses of occupation at the end of rehabilitation. The sensitivity of the WS to predict poor occupational outcome was 61.5 % while its specificity was 59.4 %. When combined with medical opinion, its sensitivity was higher (75 %) with a specificity of only 50.9 %. Regarding the prediction of further need for rehabilitation, the WS had a sensitivity of 56.3 % and specificity 76.4 %. Combined with the medical assessment, the sensitivity increased to 76.5 %, whereas the specificity was slightly lower with 76,1 %. Neither the WS alone nor the combination with a medical assessment allows valid prognoses of occupational problems and further rehabilitation needs at the beginning of rehabilitation. This suggests that the validity of the WS, which has been demonstrated for other indications, does not simply apply to neurological rehabilitation. Further studies are necessary to determine the validity of this scale.

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