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- Dokumenttyp:
- Case Reports; Journal Article; Article
- Autor(en):
- Robu, Stephanie; Schottelius, Margret; Eiber, Matthias; Maurer, Tobias; Gschwend, Jürgen; Schwaiger, Markus; Wester, Hans-Jürgen
- Titel:
- Preclinical Evaluation and First Patient Application of 99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer.
- Abstract:
- Initial studies in patients have demonstrated the suitability of (111)In-PSMA-I&T ((111)In-DOTAGA-(3-iodo-y)-f-k-Sub(KuE)) (PSMA is prostate-specific membrane antigen and I&T is imaging and therapy) for radioguided surgery (RGS) of small metastatic prostate cancer (PCa) soft-tissue lesions. To meet the clinical need for a more cost-effective alternative, the PSMA-I&T-based tracer concept was adapted to (99m)Tc-labeling chemistry. Two PSMA-I&T-derived inhibitors with all-L-serine- (MAS3) and all-D-serine- (mas3) chelating moieties were evaluated in parallel, and a kit procedure for routine (99m)Tc labeling was developed.PSMA affinities (IC50) and internalization kinetics of (99m)Tc-MAS3-y-nal-k(Sub-KuE) and (99m)Tc-mas3-y-nal-k(Sub-KuE) ((99m)Tc-PSMA-I&S for imaging and surgery) were determined using LNCaP cells and ((125)I-BA)KuE as a radioligand and reference standard. In vivo metabolite analyses and biodistribution studies were performed using CD-1 nu/nu and LNCaP tumor-bearing CB-17 severe combined immunodeficiency mice. The pharmacokinetics of (99m)Tc-PSMA-I&S in humans were investigated in a patient with advanced metastatic PCa via sequential planar whole-body SPECT imaging at 1, 3, 5, and 21 h after injection. Additionally, preoperative SPECT/CT (12 h after injection) and (99m)Tc-PSMA-I&S-supported RGS (16 h after injection) were performed in 1 PCa patient with proven iliac and inguinal lymph node metastases.A robust and reliable kit-labeling procedure was established, allowing the preparation of (99m)Tc-MAS3-y-nal-k(Sub-KuE) and (99m)Tc-PSMA-I&S in consistently high radiochemical yield and purity (>=98%, n > 50 preparations). Because of its improved internalization efficiency and superior in vivo stability, (99m)Tc-PSMA-I&S was selected for further in vivo evaluation. Compared with (111)In-PSMA-I&T, (99m)Tc-PSMA-I&S showed delayed clearance kinetics but identical uptake in PSMA-positive tissues in the LNCaP xenograft model (1 h after injection). In exemplary PCa patients, a relatively slow whole-body clearance of (99m)Tc-PSMA-I&S was observed due to high plasma protein binding (94%) of the tracer. This, however, promoted efficient tracer uptake in PCa lesions over time and led to steadily increasing lesion-to-background ratios up to 21 h after injection. Preoperative SPECT/CT showed a high (99m)Tc-PSMA-I&S uptake in all suspect lesions identified in previous (68)Ga-HBED-CC-Ahx-KuE ((68)Ga-HBED-CC-PSMA) PET/CT, allowing for their successful intraoperative detection and resection during first-in-human RGS.Because of a straightforward and reliable kit production, (99m)Tc-PSMA-I&S represents a cost-effective, readily available alternative to (111)In-PSMA-I&T. Initial patient data indicate its comparable or even superior performance as a probe for PSMA-targeted RGS and also hint toward the unexpected potential of (99m)Tc-PSMA-I&S as a SPECT imaging agent.
- Zeitschriftentitel:
- J Nucl Med
- Jahr:
- 2017
- Band / Volume:
- 58
- Heft / Issue:
- 2
- Seitenangaben Beitrag:
- 235-242
- Sprache:
- eng
- Volltext / DOI:
- doi:10.2967/jnumed.116.178939
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/27635024
- Print-ISSN:
- 0161-5505
- TUM Einrichtung:
- Klinik und Poliklinik für Nuklearmedizin; Urologische Klinik und Poliklinik
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