Comparison of three radiolabelled peptide analogues for CCK-2 receptor scintigraphy in medullary thyroid carcinoma

• Published in: European journal of nuclear medicine and molecular imaging Vol. 36; no. 8; pp. 1265 - 1272
• Main Authors: Fröberg, Alida C., de Jong, Marion, Nock, Berthold A., Breeman, Wout A. P., Erion, Jack L., Maina, Theodosia, Verdijsseldonck, Marion, de Herder, Wouter W., van der Lugt, Aad, Kooij, Peter P. M., Krenning, Eric P.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-08-2009; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Amino Acid Sequence; Brain Stem Neoplasms - diagnostic imaging; Brain Stem Neoplasms - metabolism; Cancer; Cardiology; Female; Humans; Imaging; Indium Radioisotopes; Isotope Labeling; Male; Medical diagnosis; Medical imaging; Medicine; Medicine & Public Health; Middle Aged; Nuclear Medicine; Oligopeptides - chemistry; Oligopeptides - metabolism; Oligopeptides - pharmacokinetics; Oncology; Original; Original Article; Orthopedics; Peptides; Radioactivity; Radiology; Radionuclide Imaging; Receptor, Cholecystokinin B - metabolism; Spleen - metabolism; Thyroid diseases; Thyroid Neoplasms - diagnostic imaging; Thyroid Neoplasms - metabolism; Tissue Distribution; Minigastrin; Cholecystokinin; CCK-2 receptor; Medullary thyroid carcinoma
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-009-1098-9

Purpose
Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in a high percentage of medullary thyroid carcinomas (MTC). Analogous to somatostatin receptors, CCK-2 receptors might be viable targets for radionuclide scintigraphy and/or radionuclide therapy. Several CCK-2 receptor-binding radiopeptides have been developed, and some have been carried through into clinical studies. However, these studies are mostly limited and difficult to compare. The aim of this study was to evaluate the diagnostic and therapeutic potential of three promising CCK-2 receptor-binding radiopeptides in patients with MTC.
Methods
111
In-DOTA-(
D
)Asp-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH
2
(
111
In-DOTA-CCK), a CCK analogue, and the gastrin-based ligands
99m
Tc-N
4
-Gly-(
D
)Glu-(Glu)
5
-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH
2
(
99m
Tc-demogastrin 2) and
111
In-DOTA-(
D
)Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH
2
(
111
In-DOTA-MG11) were each administered to the same group of six patients. Planar images made at 3–5, 7 and 24 h p.i. were used for comparison of tumour visualisation and renal uptake.
Results
99m
Tc-demogastrin 2 scintigraphy visualised all known lesions and new lesions in four of six patients.
111
In-DOTA-CCK and
111
In-DOTA-MG11 on the other hand missed several lesions; tumour uptake of these two radiopharmaceuticals was quite low. Comparison of retention of renal activity showed no major differences between the three radiopeptides.
Conclusion
99m
Tc-demogastrin 2 scintigraphy appeared most promising as a diagnostic tool in patients with MTC. Further studies are required to evaluate its value in patient management. Direct comparisons of the compounds studied strongly suggests that
111
In-DOTA-CCK and
111
In-DOTA-MG11 have less potential as imaging agents than
99m
Tc-demogastrin 2. These DOTA-linked compounds are considered unlikely to be useful for radionuclide therapy because of low tumour uptake.