Related Experiment Video
Updated: Jul 5, 2026
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
203Pb-labeled alpha-melanocyte-stimulating hormone peptide as an imaging probe for melanoma detection
Yubin Miao1, Said D Figueroa, Darrell R Fisher
1Department of Dermatology, University of New Mexico, Albuquerque, New Mexico 87131, USA. ymiao@salud.unm.edu
Unlabelled:
Peptide-targeted alpha-therapy with 7.4 MBq of (212)Pb-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-ReO-[Cys(3,4,10),d-Phe(7),Arg(11)]alpha-MSH(3-13) ((212)Pb-DOTA-Re(Arg(11))CCMSH) cured 45% of B16/F1 murine melanoma-bearing C57 mice in a 120-d study, highlighting its melanoma treatment potential. However, there is a need to develop an imaging surrogate for patient-specific dosimetry and to monitor the tumor response to (212)Pb-DOTA-Re(Arg(11))CCMSH therapy. The purpose of this study was to evaluate the potential of (203)Pb-DOTA-Re(Arg(11))CCMSH as a matched-pair SPECT agent for (212)Pb-DOTA-Re(Arg(11))CCMSH.
Methods:
DOTA-Re(Arg(11))CCMSH was labeled with (203)Pb in 0.5 M NH(4)OAc buffer at pH 5.4. The internalization and efflux of (203)Pb-DOTA-Re(Arg(11))CCMSH were determined in B16/F1 melanoma cells. The pharmacokinetics of (203)Pb-DOTA-Re(Arg(11))CCMSH was examined in B16/F1 melanoma-bearing C57 mice. A micro-SPECT/CT study was performed with (203)Pb-DOTA-Re(Arg(11))CCMSH in a B16/F1 melanoma-bearing C57 mouse at 2 h after injection.
Results:
(203)Pb-DOTA-Re(Arg(11))CCMSH was easily prepared in NH(4)OAc buffer and completely separated from the excess nonradiolabeled peptide by reversed-phase high-performance liquid chromatography (RP-HPLC). (203)Pb-DOTA-Re(Arg(11))CCMSH displayed fast internalization and extended retention in B16/F1 cells. Approximately 73% of (203)Pb-DOTA-Re(Arg(11))CCMSH activity internalized after a 20-min incubation at 25 degrees C. After incubation of the cells in culture medium for 20 min, 78% of internalized activity remained in the cells. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a biodistribution pattern similar to that of (212)Pb-DOTA-Re(Arg(11))CCMSH in B16/F1 melanoma-bearing mice. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a peak tumor uptake of 12.00+/-3.20 percentage injected dose per gram (%ID/g) at 1 h after injection. The tumor uptake gradually decreased to 3.43+/-1.12 %ID/g at 48 h after injection. (203)Pb-DOTA-Re(Arg(11))CCMSH exhibited a peak tumor-to-kidney uptake ratio of 1.53 at 2 h after injection. The absorbed doses to the tumor and kidneys were 4.32 and 4.35 Gy, respectively, per 37 MBq. Whole-body clearance of (203)Pb-DOTA-Re(Arg(11))CCMSH was fast, with approximately 89% of the injected activity cleared through the urinary system by 2 h after injection. (203)Pb showed 1.6-mm SPECT resolution, which was comparable to (99m)Tc. Melanoma lesions were visualized through SPECT/CT images of (203)Pb-DOTA-Re(Arg(11))CCMSH at 2 h after injection.
Conclusion:
(203)Pb-DOTA-Re(Arg(11))CCMSH exhibited favorable pharmacokinetic and tumor imaging properties, highlighting its potential as a matched-pair SPECT agent for (212)Pb-DOTA-Re(Arg(11))CCMSH melanoma treatment.
Insights
This study introduces (203)Pb-DOTA-Re(Arg(11))CCMSH as a SPECT imaging agent to monitor alpha-therapy for melanoma. It shows promising tumor uptake and clearance, supporting its use for patient-specific dosimetry and treatment response assessment.
Area of Science:
- Nuclear Medicine
- Radiopharmaceutical Chemistry
- Oncology
Background:
- Peptide-targeted alpha-therapy using (212)Pb-DOTA-Re(Arg(11))CCMSH shows potential for melanoma treatment.
- A need exists for an imaging surrogate to guide patient-specific dosimetry and monitor treatment response.
Purpose of the Study:
- To evaluate (203)Pb-DOTA-Re(Arg(11))CCMSH as a matched-pair SPECT imaging agent for (212)Pb-DOTA-Re(Arg(11))CCMSH alpha-therapy.
Main Methods:
- DOTA-Re(Arg(11))CCMSH was labeled with (203)Pb.
- In vitro studies assessed internalization and efflux in B16/F1 melanoma cells.
- In vivo pharmacokinetic and biodistribution studies were conducted in tumor-bearing mice.
- Micro-SPECT/CT imaging was performed.
Main Results:
- (203)Pb-DOTA-Re(Arg(11))CCMSH demonstrated rapid internalization and sustained retention in melanoma cells.
- Biodistribution in mice mirrored that of the therapeutic (212)Pb agent, with peak tumor uptake of 12.00±3.20 %ID/g at 1 hour.
- SPECT/CT imaging successfully visualized melanoma lesions with good resolution (1.6 mm).
Conclusions:
- (203)Pb-DOTA-Re(Arg(11))CCMSH exhibits favorable pharmacokinetics and tumor imaging characteristics.
- It holds significant potential as a SPECT imaging surrogate for (212)Pb-based alpha-therapy in melanoma.
- This agent can aid in dosimetry and monitoring therapeutic efficacy.
