Prediction of Response to 177Lu-PSMA Therapy Based on Tumor-to-Kidney Ratio on Pretherapeutic PSMA PET/CT and Posttherapeutic Tumor-Dose Evaluation in mCRPC.

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.

An 89Zr-Labeled PSMA Tracer for PET/CT Imaging of Prostate Cancer Patients.

The short half-life of existing prostate-specific membrane antigen (PSMA) tracers limits their time for internalization into tumor cells after injection, which is an essential prerequisite for robust detection of tumor lesions with low PSMA expression on PET/CT scans. Because of its longer half-life, the 89Zr-labeled ligand 89Zr-PSMA-DFO allows acquisition of PET scans up to 6 d after injection, thereby overcoming the above limitation. We investigated whether 89Zr-PSMA-DFO allowed more sensitive detection of weak PSMA-positive prostate cancer lesions. Methods: We selected 14 prostate cancer patients with biochemical recurrence who exhibited no PSMA-positive lesions on a PET scan acquired with existing PSMA tracers (68Ga-PSMA-11, 18F-JK-PSMA-7). Within 5 wk after the negative scan result, we obtained a second PSMA PET scan using 89Zr-PSMA-DFO (117 ± 16 MBq, PET acquisition within 6 d of injection). Results:89Zr-PSMA-DFO detected 15 PSMA-positive lesions in 8 of 14 patients, who had a PET-negative reading of their initial PET scans with existing tracers. In these 8 patients, the new scans revealed localized recurrence of disease (3/8), metastases in lymph nodes (3/8), or lesions at distant sites (2/8). On the basis of these results, patients received lesion-targeted radiotherapies (5/8), androgen deprivation therapies (2/8), or no therapy (1/8). The plausibility of 14 of 15 lesions was supported by histology, clinical follow-up after radiotherapy, or subsequent imaging. Furthermore, comparison of the 15 89Zr-PSMA-DFO-positive lesions with their correlates on the original PET scan revealed that established tracers exhibited mild accumulation in 7 of 15 lesions; however, contrast-to-noise ratios were too low for robust detection of these lesions (contrast-to-noise ratios, 2.4 ± 3.7 for established tracers vs. 10.2 ± 8.5 for 89Zr-PSMA-DFO, P = 0.0014). The SUVmax of the 15 89Zr-PSMA-DFO-positive lesions (11.5 ± 5.8) was significantly higher than the SUVmax on the original PET scans (4.7 ± 2.8, P = 0.0001). Kidneys were the most exposed organ, with doses of 3.3 ± 0.7 mGy/MBq. The effective dose was 0.15 ± 0.04 mSv/MBq. Conclusion: In patients with weak PSMA expression, a longer period of time might be needed for ligand internalization than that offered by existing PSMA tracers to make lesions visible on PET/CT scans. Hence, 89Zr-PSMA-DFO might be of significant benefit to patients in whom the search for weak PSMA-positive lesions is challenging. Radiation exposure should be weighed against the potential benefit of metastasis-directed therapy or salvage radiotherapy, which we initiated in 36% (5/14) of our patients based on their 89Zr-PSMA-DFO PET scans.

Translational Development of a Zr-89-Labeled Inhibitor of Prostate-specific Membrane Antigen for PET Imaging in Prostate Cancer.

PURPOSE: We present here a Zr-89-labeled inhibitor of prostate-specific membrane antigen (PSMA) as a complement to the already established F-18- or Ga-68-ligands. PROCEDURES: The precursor PSMA-DFO (ABX) was used for Zr-89-labeling. This is not an antibody, but a peptide analogue of the precursor for the production of [177Lu]Lu-PSMA-617. The ligand [89Zr]Zr-PSMA-DFO was compared with [68Ga]Ga-PSMA-11 and [18F]F-JK-PSMA-7 in vitro by determination of the Kd value, cellular uptake, internalization in LNCaP cells, biodistribution studies with LNCaP prostate tumor xenografts in mice, and in vivo by small-animal PET imaging in LNCaP tumor mouse models. A first-in-human PET was performed with [89Zr]Zr-PSMA-DFO on a patient presenting with a biochemical recurrence after brachytherapy and an ambiguous intraprostatic finding with [18F]F-JK-PSMA-7 but histologically benign cells in a prostate biopsy 7 months previously. RESULTS: [89Zr]Zr-PSMA-DFO was prepared with a radiochemical purity ≥ 99.9% and a very high in vitro stability for up to 7 days at 37 °C. All radiotracers showed similar specific cellular binding and internalization, in vitro and comparable tumor uptake in biodistribution experiments during the first 5 h. The [89Zr]Zr-PSMA-DFO achieved significantly higher tumor/background ratios in LNCaP tumor xenografts (tumor/blood: 309 ± 89, tumor/muscle: 450 ± 38) after 24 h than [68Ga]Ga-PSMA-11 (tumor/blood: 112 ± 57, tumor/muscle: 58 ± 36) or [18F]F-JK-PSMA-7 (tumor/blood: 175 ± 30, tumor/muscle: 114 ± 14) after 4 h (p < 0.01). Small-animal PET imaging demonstrated in vivo that tumor visualization with [89Zr]Zr-PSMA-DFO is comparable to [68Ga]Ga-PSMA-11 or [18F]F-JK-PSMA-7 at early time points (1 h p.i.) and that PET scans up to 48 h p.i. clearly visualized the tumor at late time points. A late [89Zr]Zr-PSMA-DFO PET scan on a patient with biochemical recurrence (BCR) had demonstrated intensive tracer accumulation in the right (SUVmax 13.25, 48 h p.i.) and in the left prostate lobe (SUV max 9.47), a repeat biopsy revealed cancer cells on both sides. CONCLUSION: [89Zr]Zr-PSMA-DFO is a promising PSMA PET tracer for detection of tumor areas with lower PSMA expression and thus warrants further clinical evaluation.

[18F]-JK-PSMA-7 PET/CT Under Androgen Deprivation Therapy in Advanced Prostate Cancer.

PURPOSE: PSMA imaging is frequently used for monitoring of androgen deprivation therapy (ADT) in prostate cancer. In a previous study, [18F]-JK-PSMA-7 exhibited favorable properties for tumor localization after biochemical recurrence. In this retrospective study, we evaluated the performance of [18F]-JK-PSMA-7 under ADT. PROCEDURES: We examined the performance of [18F]-JK-PSMA-7 in 70 patients (first cohort) with increasing or detectable PSA values under ADT (PSA < 2 ng/ml for 21/70 patients). We further analyzed 58 independent patients with PSA levels < 2 ng/ml under ADT, who were imaged with [68Ga]PSMA-11 or [18F]DCFPyL (second cohort). Finally, we compared detection rates between [18F]-JK-PSMA-7, [68Ga]PSMA-11, and [18F]DCFPyL. RESULTS: In the first cohort, we detected [18F]-JK-PSMA-7-positive lesions in 63/70 patients. In patients with PSA levels ≥ 2 ng/ml, the detection rate was 100 % (49/49). In patients with PSA < 2 ng/ml, the detection rate was significantly lower (66.7 %, 14/21, p = 9.7 × 10-5) and dropped from 85.7 % (12/14, PSA levels between 0.3 and 2.0 ng/ml) to 28.6 % (2/7) for PSA levels < 0.3 ng/ml (p = 1.73 × 10-2). In the second cohort (PSA < 2 ng/ml), the detection rate was 79.3 % (46/58) for [68Ga]PSMA-11 or [18F]DCFPyL. Again, the detection rate was significantly higher (p = 1.1 × 10-2) for patients with PSA levels between 0.3 and 2.0 ng/ml (87.0 %, 40/46) relative to those with PSA levels < 0.3 ng/ml (50 %, 6/12). No significant difference was found between [18F]-JK-PSMA-7 and [68Ga]PSMA-11 or [18F]DCFPyL in patients with PSA levels < 2 ng/ml (p = 0.4295). CONCLUSION: [18F]-JK-PSMA-7 PET showed a high detection rate in patients with PSA levels ≥ 0.3 ng/ml under ADT. The lower PSA threshold of 0.3 ng/ml for high detection rates was consistent across the three PSMA ligands. Thus, PSMA imaging is suitable for clinical follow-up of patients with increasing PSA levels under ADT.

Semiautomatic algorithm for lymph node analysis corrected for partial volume effects in combined positron emission tomography-computed tomography.

Positron emission tomography-computed tomography (PET-CT) is superior compared to stand-alone PET in evaluation of malignancies. Few studies have employed high-resolution structural information to correct PET. We designed a semiautomatic algorithm using CT and PET to obtain a partial volume corrected (PVC) standardized uptake value (SUV) and a combined morphologic and functional parameter (multimodal SUV) for lymph node assessment. Lesions were segmented by a semiautomatic algorithm in CT images. Lesion volume was used for PVC and for calculating the multimodal SUV. The method was applied to 47 lymph nodes (30 patients) characterized as suspicious in 18F-fluorodeoxyglucose-PET-CT. In phantoms, PVC improved significantly the measured uptake of the lesion. In patients, 36 lymph nodes could be segmented without problems; in 11 lesions, a manual interaction was necessary. SUVs before PVC (mean 1.29) increased significantly (p < .0005) after PVC (mean 2.8). If SUV 2.5 was used as a threshold value to distinguish between benign and malignant lesions, 11 of the 47 lesions changed from benign to malignant after the PVC. The mean multimodal SUV was 0.39 mL for the benign lesions and 4.47 mL for the malignant lesions. In this work we presented a method for quantitative analysis of lymph nodes in PET-CT. PVC leads to significant differences in SUV.

An 18F-Labeled PSMA Ligand for PET/CT of Prostate Cancer: First-in-Humans Observational Study and Clinical Experience with 18F-JK-PSMA-7 During the First Year of Application.

In preclinical trials, the recently developed tracer 2-methoxy-18F-DCFPyL (18F-JK-prostate-specific membrane antigen [PSMA]-7) has shown favorable properties regarding clinical performance and radiochemical accessibility. The aim of this study was to evaluate the clinical utility of 18F-JK-PSMA-7 for PET/CT imaging of patients with prostate cancer. Methods: In an Institutional Review Board-approved pilot study, the initial clinical utility of PET/CT imaging with 18F-JK-PSMA-7 was directly compared with 68Ga-PSMA-11 PET/CT in a group of 10 patients with prostate cancer. The 2 PSMA tracers were administered to each patient less than 3 wk apart. Next, we analyzed the data of 75 consecutive patients who had undergone clinical 18F-JK-PSMA-7 PET/CT imaging for tumor localization of biochemical recurrence (BCR). Results: The pilot study in 10 patients who were examined with both PSMA tracers demonstrated that 18F-JK-PSMA-7 was at least equivalent to 68Ga-PSMA-11. All unequivocally 68Ga-PSMA-11-positive lesions could be also detected using 18F-JK-PSMA-7, and in 4 patients additional suspected PSMA-positive lesions were identified (1 patient changed from PSMA-negative to PSMA-positive). In patients with BCR (after prostatectomy or radiotherapy), the capacity of 18F-JK-PSMA-7 PET/CT to detect at least one PSMA-positive lesion was 84.8%. The prostate-specific antigen (PSA)-stratified detection rate of 18F-JK-PSMA-7 after prostatectomy varied among 54.5% (6/11 patients; PSA < 0.5 µg/L), 87.5% (14/16 patients; PSA 0.5-2 µg/L), and 90.9% (20/22 patients; PSA > 2 µg/L). Conclusion: The tracer 18F-JK-PSMA-7 was found to be safe and clinically useful. We demonstrated that 18F-JK-PSMA-7 was not inferior when directly compared with 68Ga-PSMA-11 in a pilot study but indeed identified additional PSMA-avid suspected lesions in oligometastasized patients with BCR. In a subsequent analysis of a clinical cohort of BCR patients, 18F-JK-PSMA-7 was useful in tumor localization. 18F-JK-PSMA-7 is recommended for future prospective trials.

Intraindividual Comparison of 18F-PSMA-1007 with Renally Excreted PSMA Ligands for PSMA PET Imaging in Patients with Relapsed Prostate Cancer.

18F-prostate-specific membrane antigen (PSMA)-1007 is excreted mainly through the liver. We benchmarked the performance of 18F-PSMA-1007 against 3 renally excreted PSMA tracers. Methods: Among 668 patients, we selected 27 in whom PET/CT results obtained with 68Ga-PSMA-11, 18F-DCFPyL (2-(3-(1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid), or 18F-JK-PSMA-7 (JK, Juelich-Koeln) were interpreted as equivocal or negative or as oligometastatic disease (PET-1). Within 3 wk, a second PET scan with 18F-PSMA-1007 was performed (PET-2). The confidence in the interpretation of PSMA-positive locoregional findings was scored on a 5-point scale, first in routine diagnostics (reader 1) and then by an independent second evaluation (reader 2). Discordant PSMA-positive skeletal findings were examined by contrast-enhanced MRI. Results: For both readers, 18F-PSMA-1007 facilitated the interpretability of 27 locoregional lesions. In PET-2, the clinical readout led to a significantly lower number of equivocal locoregional lesions (P = 0.024), and reader 2 reported a significantly higher rate of suspected lesions that were falsely interpreted as probably benign in PET-1 (P = 0.023). Exclusively in PET-2, we observed a total of 15 PSMA-positive spots in the bone marrow of 6 patients (22%). None of the 15 discordant spots had a morphologic correlate on the corresponding CT scan or on the subsequent MRI scan. Thus, 18F-PSMA-1007 exhibits a significantly higher rate of unspecific medullary spots (P = 0.0006). Conclusion:18F-PSMA-1007 may increase confidence in interpreting small locoregional lesions adjacent to the urinary tract but may decrease the interpretability of skeletal lesions.

Thyroid Uptake and Effective Half-Life of Radioiodine in Thyroid Cancer Patients at Radioiodine Therapy and Follow-Up Whole-Body Scintigraphy Either in Hypothyroidism or Under rhTSH.

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.

[Procedural guideline for Iodine-131 whole-body scintigraphy in differentiated thyroid carcinoma (version 5)]. / Verfahrensanweisung für die Iod-131 Ganzkörperszintigrafie beim differenzierten Schilddrüsenkarzinom (Version 5).

Version 5 of the procedural guideline for Iodine-131 whole-body scintigraphy (WBS) in differentiated thyroid carcinoma is an update of the version 4, published by the "Deutsche Gesellschaft für Nuklearmedizin" (DGN). This procedural guideline advises on how to best perform I-131 whole body scintigraphy after I-131 therapy or after application of a diagnostic I-131 activity. A representative expert group has discussed and reached consensus on the procedural guideline; the development of this procedural guideline therefore fulfils the criteria for level S1 (first step) within the classification of the German Workgroup of Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften"; AWMF).

4D-CT-based motion correction of PET images using 3D iterative deconvolution.

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.

Discovery of 18F-JK-PSMA-7, a PET Probe for the Detection of Small PSMA-Positive Lesions.

Prostate-specific membrane antigen (PSMA), expressed by most prostate carcinomas (PCa), is a promising target for PCa imaging. The application of PSMA-specific 18F-labeled PET probes such as 18F-DCFPyL and 18F-PSMA-1007 considerably improved the accuracy of PCa tumor detection. However, there remains a need for further improvements in sensitivity and specificity. The aim of this study was the development of highly selective and specific PSMA probes with enhanced imaging properties, in comparison with 18F-DCFPyL, 18F-PSMA-1007, and 68Ga-PSMA-11. Methods: Eight novel 18F-labeled PSMA ligands were prepared. Their cellular uptake in PSMA-positive LNCaP C4-2 and PSMA-negative PC-3 cells was compared with that of 18F-DCFPyL. The most promising candidates were additionally evaluated by small-animal PET in healthy rats using PSMA-positive peripheral ganglia as a model for small PCa lesions. PET images of the ligand with the best outcome, 18F-JK-PSMA-7, were compared with those of 18F-DCFPyL, 18F-PSMA-1007, and 68Ga-PSMA-11 with respect to key image-quality parameters for the time frame 60-120 min. Results: Compared with 18F-DCFPyL, 18F-JK-PSMA-7 demonstrated increased PSMA-specific cellular uptake. Although target-to-background ratios of 18F-DCFPyL and 18F-PSMA-1007 were comparable, this parameter was higher for 18F-JK-PSMA-7 and lower for 68Ga-PSMA-11. Image acutance was significantly higher for 18F-JK-PSMA-7 and 18F-PSMA-1007 than for 18F-DCFPyL and 68Ga-PSMA-11. Image resolution was similar for all 4 tracers. 18F-PSMA-1007 demonstrated significantly higher blood protein binding and bone uptake than the other tracers. Conclusion:18F-JK-PSMA-7 is a promising candidate for high-quality visualization of small PSMA-positive lesions. Excellent preclinical imaging properties justify further preclinical and clinical studies of this tracer.

Biodistribution and radiation dosimetry of [18F]-JK-PSMA-7 as a novel prostate-specific membrane antigen-specific ligand for PET/CT imaging of prostate cancer.

AIM: 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. 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]-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). 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 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. CONCLUSIONS: 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.

Impact of different approaches to calculation of treatment activities on achieved doses in radioiodine therapy of benign thyroid diseases.

PURPOSE: Radioiodine has been used for the treatment of benign thyroid diseases for over 70 years. 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. METHODS: Pretherapeutic 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. RESULTS: The 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. CONCLUSION: Elaborate 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.

Uptake in non-affected bone tissue does not differ between [18F]-DCFPyL and [68Ga]-HBED-CC PSMA PET/CT.

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.

Lacrimal Glands May Represent Organs at Risk for Radionuclide Therapy of Prostate Cancer with [(177)Lu]DKFZ-PSMA-617.

PURPOSE: 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 [(177)Lu]DKFZ-PSMA-617 therapy in a small cohort of patients with metastatic prostate cancer. PROCEDURES: Nine patients with a history of prostate cancer documented by histopathology and radiologic evidence of metastatic diseases underwent radioligand therapy with [(177)Lu]DKFZ-PSMA-617. Conjugated planar whole-body scintigraphies acquired at 0.5, 24, 48, 72, and 168 h post-injection were analyzed by regions of interest, and time-activity curves were generated for various organs. Cumulated activities and residence times were calculated by bi-exponential fit of the time-activity curves. Mean absorbed doses were finally estimated using OLINDA/EXM1.1™. Additionally, the uncertainty when omitting the last measurement (168 h p.i.) was studied. RESULTS: The following mean absorbed doses were calculated: 2.82 mGy/MBq for the lacrimal glands, 0.72 mGy/MBq for the salivary glands, 0.53 mGy/MBq for the kidneys, and 0.42 mGy/MBq for the nasal mucous membrane. Omitting the last measurement resulted in a mean deviation of 10 to 25 % for absorbed dose values as compared to the ones received by analyzing all measurements. CONCLUSION: Absorbed organ doses of [(177)Lu]DKFZ-PSMA-617 therapy are not likely to be critical for kidneys, salivary glands, and the nasal mucous membrane. The lacrimal glands may represent the dose-limiting organs. Whole-body scintigraphy appears sufficient for dose estimation, but late measurements are mandatory, if accurate dose calculation is required.