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.

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.