The aim of this study was to analyze the absorbed dose of 177Lu-PSMA in osseous versus lymphatic metastases in patients with metastatic castration-resistant prostate cancer across therapy cycles and to relate those data to therapeutic success. In addition, pretherapeutic prostate-specific membrane antigen (PSMA) PET/CT was evaluated for its ability to predict response behavior. Methods: The study comprised 30 patients with metastatic castration-resistant prostate cancer, each receiving at least 3 cycles of 177Lu-PSMA therapy. Prostate-specific antigen (PSA) values between baseline and 6 wk after the third therapy cycle were used to classify the patients as responders (PSA decline ≥ 50%) or nonresponders (unchanged or increasing PSA level). Quantitative SPECT/CT images were acquired 24, 48, and 168 h after application of 177Lu-PSMA. The absorbed dose for tumor lesions was calculated with dosimetry software. From the pretherapeutic PET/CT scan, the tumor-to-kidney uptake ratio was determined for different SUVs. Results: Regardless of patient response, the kidneys received a mean dose of 0.55 ± 0.20 Gy/GBq per cycle. In the first therapy cycle, the lymph node lesions received a mean dose of 3.73 ± 1.65 Gy/GBq in responders and 1.86 ± 1.25 Gy/GBq in nonresponders (P < 0.01). For bone lesions, the respective mean doses were 3.47 ± 2.00 Gy/GBq and 1.48 ± 0.95 Gy/GBq (P < 0.01). When successive therapy cycles were compared, the mean dose was found to have been reduced from the first to the second cycle by 27% for lymph nodes and by 33% for bone lesions. A significant difference (P < 0.01) in the ratio of lymph node and bone lesion uptake to kidney uptake between responders and nonresponders could be deduced from the pretherapeutic PET/CT scan. Conclusion: Significantly higher doses were achieved for lymph node and bone lesions in responders. The highest absorbed dose, for both lymphatic and osseous lesions, was achieved in the first cycle, decreasing in the second therapy cycle thereafter despite unchanged therapy activities. It may be possible to estimate the response to therapy from the ratio of tumor uptake to kidney uptake obtained from the pretherapeutic PSMA PET/CT scans.

Objectives Positron emission tomography acquisition takes several minutes representing an image averaged over multiple breathing cycles. Therefore, in areas influenced by respiratory movement, PET-positive lesions occur larger, but less intensive than they actually are, resulting in false quantitative assessment. We developed a motion-correction algorithm based on 4D-CT without the need to adapt PET-acquisition. Methods The algorithm is based on a full 3D iterative Richardson-Lucy-Deconvolution using a point-spread-function constructed using the motion information obtained from the 4D-CT. In a motion phantom study (3 different hot spheres in background activity), optimal parameters for the algorithm in terms of number of iterations and start image were estimated. Finally, the correction method was applied to 3 patient data sets. In phantom and patient data sets lesions were delineated and compared between motion corrected and uncorrected images for activity uptake and volume. Results Phantom studies showed best results for motion correction after 6 deconvolution steps or higher. In phantom studies, lesion volume improved up to 23% for the largest, 43% for the medium and 49% for the smallest sphere due to the correction algorithm. In patient data the correction resulted in a significant reduction of the tumor volume up to 33.3 % and an increase of the maximum and mean uptake of the lesion up to 62.1 and 19.8 % respectively. Conclusion In conclusion, the proposed motion correction method showed good results in phantom data and a promising reduction of detected lesion volume and a consequently increasing activity uptake in three patients with lung lesions.

We investigated the whole-body distribution and the radiation dosimetry of [18F]-JK-PSMA-7, a novel 18F-labeled PSMA-ligand for PET/CT imaging of prostate cancer. Ten patients with prostate cancer and biochemical recurrence or radiologic evidence of metastatic diseases were examined with 329–384 MBq (mean 359 ± 17 MBq) [18F]-JK-PSMA-7. Eight sequential positron emission tomography (PET) scans were acquired from 20 min to 3 h after injection with IRB approval. The kidneys, liver, lungs, spleen, and salivary glands were segmented into volumes of interest using the QDOSE dosimetry software suite (ABX-CRO, Germany). Absorbed and effective dose were calculated using the ICRP-endorsed IDAC 1.0 package. The absorbed dose of the salivary glands was determined using the spherical model of OLINDA 1.1. PSMA-positive lesions were evaluated separately. Quantitative assessment of the uptake in suspicious lesions was performed by analysis of maximum (max) and peak SUV values. The gluteus maximus muscle (SUVmean) served as a reference region for the calculation of tumor-to-background ratios (TBR’s). Physiologic radiotracer accumulation was observed in the salivary and lacrimal glands, liver, spleen, and intestines, in a pattern resembling the distribution known from other PSMA-tracers with excretion via urinary and biliary pathways. The effective dose from [18F]-JK-PSMA-7 for the whole body was calculated to be 1.09E−02 mGy/MBq. The highest radiation dose was observed in the kidneys (1.76E−01 mGy/MBq), followed by liver (7.61E−02 mGy/MBq), salivary glands (4.68E−02 mGy/MBq), spleen (1.89E−02 mGy/MBq), and lungs (1.10E-2 mGy/MBq). No adverse effects of tracer injection were observed. Six out of ten patients were scored as PSMA-positive. A total of 18 suspicious lesions were analyzed, which included six bone lesions, nine lymph nodes, and three local lesions within the prostate fossa. The values for the SUVmax and SUVpeak in the PSMA-positive lesions increased until 60 min p.i. and remained at this intensity in the PET/CT scans until 140 min. In the period between 170 and 200 min after injection, a further significant increase in SUVmax and SUVpeak within the PSMA-positive lesions was observed. The highest TBR of [18F]-JK-PSMA-7 was found 3 h after injection. From the kinetically collected data, it can be concluded that this trend may also continue in the further course. The start of the PET/CT acquisition should be chosen as late as possible. The high uptake in suspicious lesions in terms of absolute SUVmax and relative TBR values indicates potentially high sensitivity of the tracer for detection of prostate cancer manifestations.

Adjuvant radioiodine therapy (RITh) for differentiated thyroid carcinoma is performed either with thyroid hormone withdrawal or with administration of recombinant human thyroid-stimulating hormone (rhTSH). Heterogeneous results have been obtained on the impact of the method of patient preparation on thyroid uptake and whole-body effective half-life. A higher radiation exposure using thyroid hormone withdrawal for several weeks compared with rhTSH was reported in prior studies. It was the aim to examine whether these findings are reproducible in a modern protocol with a short interval between surgery and RITh. Methods: A retrospective study was performed on patients admitted for adjuvant RITh for differentiated thyroid carcinoma at the University Hospital of Cologne over a 5-y period from 2010. Dose rate measurements were analyzed for 366 patients, and subgroup analyses were performed for papillary thyroid cancer (n = 341) and follicular thyroid cancer (n = 25) patients, sex, length of hypothyroidism, and normal versus decreased glomerular filtration rate (GFR). Results: The median interval between surgery and RITh was 18 d for thyroid hormone withdrawal and 25 d for rhTSH (P < 0.01). The mean thyroid uptake was 4.2% ± 1.8% for the 300 hypothyroid patients versus 3.8% ± 1.6% (P = 0.12) for the 66 rhTSH patients. Whole-body half-life in the hypothyroid group was significantly longer at 19.3 ± 7.7 h versus 16.4 ± 4.6 h in the rhTSH group (P < 0.01). Results were predominantly influenced by data from the largest subgroup, that is, female papillary thyroid cancer patients. Within this group, whole-body half-life was significantly shorter in the rhTSH treatment arm. Duration of hypothyroidism and a decrease in GFR less than 60 mL/min/1.73 m2 significantly influenced results, with an increased whole-body half-life occurring in the hypothyroid group. When patients returned for whole-body scintigraphy, thyroid, half-life, and whole-body half-life were significantly shorter in the rhTSH groups, resulting in a low thyroid and remaining-body dose. Conclusion: With a shortening of the time between surgery and adjuvant RITh, thyroid uptake is not significantly changed but whole-body half-life becomes longer in the hypothyroid group. Radiation exposure for most patients is not significantly different. However, patients with a hypothyroid phase of more than 4 wk, and in particular those with a decreased GFR, experience higher radiation exposure.

88 Objectives: We investigated the whole-body distribution and the radiation dosimetry of 18F-PSMA-7, a novel 18F-labeled PSMA-ligand for the PET/CT imaging of prostate cancer. Methods: Ten patients with prostate cancer and biochemical recurrence or radiologic evidence of metastatic diseases were examined with 329 - 384 MBq (mean 359 ± 17 MBq) 18F-PSMA-7. Eight sequential positron emission tomography scans were acquired from 30 minutes to 3 hours after injection with IRB approval. Kidneys, liver, spleen and salivary glands were segmented into volumes of interest using the QDOSE dosimetry software suite (ABX-CRO, Germany). Absorbed and effective dose were calculated using the ICRP endorsed IDAC 1.0 package. The absorbed dose of the salivary glands was determined using the spherical model of OLINDA 1.1. PSMA-positive lesions were evaluated separately. Quantitative assessment of the uptake in suspicious lesions was performed by analysis of maximum (max) and peak SUV values. The gluteus maximus muscle (SUVmean) served as a reference region for the calculation of the tumor-to-background ratios (TBR’s). Results: Physiologic radiotracer accumulation was observed in the salivary and lacrimal glands, liver, spleen and intestines, in a pattern resembling the distribution known from other PSMA-tracers with excretion via biliary and urinary pathways. The effective dose from 18F-PSMA-7 for the whole body was calculated with 9.75E-03 mGy/MBq. The highest radiation dose was observed in the kidneys (1.74E-01 mGy/MBq), followed by liver (7.11E-02 mGy/MBq), salivary glands (4.82E-02 mGy/MBq) and spleen (1.44E-02 mGy/MBq). No adverse effects to tracer injection were observed. Six out of ten patients were scored as PSMA-positive. A total of nine suspicious lesions were analyzed which included two bone lesions, five lymph nodes and two local lesions within the prostate fossa. The values for the SUVmax (mean 7.59 ± 3.92) and SUVpeak (mean 3.85 ± 2.35) in the PSMA-positive lesions increased until 60 min p.i. (SUVmax 12.81 ± 7.69, SUVpeak 5.75 ± 3.22) and remained at this intensity in the subsequent PET/CT scans. Due to the decreasing activity within the background, the highest TBR’s were seen in the latest PET/CT scans (3 h p.i.). Compared to early PET/CT scans TBR’s (1 h p.i. mean 10.32 ± 6.86, 3 h p.i. mean 33.63 ± 15.81) were increased in mean by a factor of 3. Conclusion: Data from this initial study demonstrated that PET imaging with 18F-PSMA-7 is safe and feasible in the clinical setting. Physiologic accumulation of the radiotracer corresponded to the known distribution of the PSMA-expressing organs. The radiation dose from 18F-PSMA-7 was similar to that from other 18F-labeled PSMA-ligands. The highest TBR was found three hours after injection. The high uptake in suspicious lesions in terms of absolute SUVmax and relative TBR values indicates potentially high sensitivity of the tracer for detection of prostate cancer manifestations. Research support: none

PurposeRadioiodine has been used for the treatment of benign thyroid diseases for over 70years. However, internationally, there is no common standard for pretherapeutic dosimetry to optimally define the individual therapy activity. Here, we analyze how absorbed tissue doses are influenced by different approaches to pretherapeutic activity calculation of varying complexity.MethodsPretherapeutic determination of treatment activity was retrospectively recalculated in 666 patients who had undergone radioiodine therapy for benign thyroid diseases (Graves' disease, non-toxic goiter, and uni- and multinodular goiter). Approaches considering none, some, or all of a set of individual factors, including target volume, maximum radioiodine uptake, and effective half-life, were applied. Assuming individually stable radioiodine kinetics, which had been monitored twice a day under therapy, hypothetically achieved tissue doses based on hypothetically administered activities resulting from the different methods of activity calculation were compared to intended target doses.ResultsThe Marinelli formula yields the smallest deviations of hypothetically achieved doses from intended target doses. Approaches taking individual target volume into consideration perform better than fixed therapy activities, which lead to high variances in achieved doses and high deviations of hypothetically achieved doses from intended target doses.ConclusionElaborate pretherapeutic dose planning, taking individual radioiodine uptake, half-life, and target volume into consideration, should be used whenever possible. The use of disease-specific fixed activities cannot be recommended. Deviations of achieved tissue doses from target doses can already be significantly lowered by application of volume-adapted treatment activities if more elaborate means are not available.

Introduction [68Ga]PSMA-HBED-CC and [18F]DCFPyL show a high potential for the detection of recurrent prostate cancer. While 18F-based tracers have several advantages in availability and image resolution, their sensitivity in the skeleton might be impaired by released [18F]fluoride due to its high bone affinity. In turn, chemically unbound trivalent 68Ga might also accumulate in osseous tissue, in cases of occupied binding sites of plasma proteins and thereby influence bone signal. Methods A comparison of average bone SUV was performed in 17 bone-negative and 4 bone-positive patients. All patients underwent PET/CT 125 minutes after application of [18F]DCFPyL and 73 minutes after application of [68Ga]PSMA-HBED-CC at another date. Results Native SUVs in unaffected bone tissue and SUVs relative to liver uptake were lower in [18F]DCFPyL (0.49) than in [68Ga]PSMA-HBED-CC scans (0.52). SUVs relative to gluteal muscles did not differ between the two tracers. Average lesional SUVs did not differ between tracers. Conclusion No difference of average bone signal intensity was observed for [18F]DCFPyL-PET/CT in comparison to [68Ga]PSMA-HBED-CC scans indicating that diagnostic assessment of the skeleton is not affected by non-specific accumulation of free [18F]fluoride or 68Ga.

Calculating the absorbed dose is important for the determination of risk and therapeutic benefit of internal radiation therapy. The aim of this study was to perform image-based absorbed dose calculation for critical organs during the first cycle of [177Lu]DKFZ-PSMA-617 therapy in a small cohort of patients with metastatic prostate cancer.

This paper presents the new synchronous language PURR, the system description language of the verification system C@S. The language is mainly based on Esterel, but extends it in several ways. These extensions are necessary to model systems at a high level of abstraction that makes state-of-the-art verification techniques applicable. Moreover, our new language directly supports transformational verification: most steps necessary to make a system description suitable for a correctness proof with a certain decision procedure or a theorem prover can be done inside our language, avoiding conflicts occurring from different semantics of different languages.

This paper presents the new synchronous language PURR, the system description language of the verification system C@S. The language is mainly based on Esterel, but extends it in several ways. These extensions are necessary to model systems at a high level of abstraction that makes stateof-the-art verification techniques applicable. Moreover, our new language directly supports transformational verification: most steps necessary to make a system description suitable for a correctness proof with a certain decision procedure or a theorem prover can be done inside our language, avoiding conflicts occurring from different semantics of different languages.