| Autor: |
Christof, Rottenburger, Guillaume P, Nicolas, Lisa, McDougall, Felix, Kaul, Michal, Cachovan, A Hans, Vija, Roger, Schibli, Susanne, Geistlich, Anne, Schumann, Tilman, Rau, Katharina, Glatz, Martin, Behe, Emanuel R, Christ, Damian, Wild |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
J Nucl Med |
| ISSN: |
1535-5667 |
| Popis: |
Treatment of patients with advanced medullary thyroid carcinoma (MTC) is still a challenge. For more than 2 decades, it has been known that the cholecystokinin 2 receptor is a promising target for the treatment of MTC with radiolabeled minigastrin analogs. Unfortunately, kidney toxicity has precluded their therapeutic application so far. In 6 consecutive patients, we evaluated with advanced 3-dimensional dosimetry whether improved minigastrin analog (177)Lu-DOTA-(d-Glu)(6)-Ala-Tyr-Gly-Trp-Nle-Asp-PheNH(2) ((177)Lu-PP-F11N) is a suitable agent for the treatment of MTC. Methods: Patients received 2 injections of about 1 GBq (∼80 μg) of (177)Lu-PP-F11N with and without a solution of succinylated gelatin (SG, a plasma expander used for nephroprotection) in a random crossover sequence to evaluate biodistribution, pharmacokinetics, and tumor and organ dosimetry. An electrocardiogram was obtained and blood count and blood chemistry were measured up to 12 wk after the administration of (177)Lu-PP-F11N to assess safety. Results: In all patients, (177)Lu-PP-F11N accumulation was visible in tumor tissue, stomach, and kidneys. Altogether, 13 tumors were eligible for dosimetry. The median absorbed doses for tumors, stomach, kidneys, and bone marrow were 0.88 (interquartile range [IQR]: 0.85–1.04), 0.42 (IQR: 0.25–1.01), 0.11 (IQR: 0.07–0.13), and 0.028 (IQR: 0.026–0.034) Gy/GBq, respectively. These doses resulted in median tumor-to-kidney dose ratios of 11.6 (IQR: 8.11–14.4) without SG and 13.0 (IQR: 10.2–18.6) with SG; these values were not significantly different (P = 1.0). The median tumor-to-stomach dose ratio was 3.34 (IQR: 1.14–4.70). Adverse reactions (mainly hypotension, flushing, and hypokalemia) were self-limiting and not higher than grade 1. Conclusion: (177)Lu-PP-F11N accumulates specifically in MTC at a dose that is sufficient for a therapeutic approach. With a low kidney and bone marrow radiation dose, (177)Lu-PP-F11N shows a promising biodistribution. The dose-limiting organ is most likely the stomach. Further clinical studies are necessary to evaluate the maximum tolerated dose and the efficacy of (177)Lu-PP-F11N. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
