Neurotensin analogues for radioisotope targeting to neurotensin receptor-positive tumors

A neurotensin analogue, or a salt thereof, of formula (I)

• X-L-Aa8-Aa9-(L)Pro-Aa11-Aa12-(L)Leu (I)
• wherein
• Aa8 is NMe-(L)Arg, Nme-(D)Arg, NMe-(L)Lys or NMe-(D)Lys, and
• the sequence Aa9-(L)Pro-Aa11-Aa12-(L)Leu differs from (L)Arg-(L)Pro-(L)Tyr-(L)Ile-(L)Leu by at least one substitution in the amino acid sequence, the substitution(s) being selected from:
• Aa9 is selected from the group consisting of (L)Lys, ψ(CH2—NH)-(L)Arg, and ψ(CH2—NH)-(L) Lys,
• Aa11 is selected from the group consisting of (D)Tyr, (L)Dmt and (D)Dmt, and
• Aa12 is selected from the group consisting of (L)Tle, (L)Leu and (L)Val,
• X is a poly(aminocarboxylate) chelating moiety selected from the group consisting of:
• i) diethylenetriamine pentaacetic acid (DTPA) and its derivatives,
• ii) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and its derivatives,
• iii) 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and its derivatives,
• iv) 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid (TETA) and its derivatives,
• v) 1,4,7,10-tetraazacyclotridecane-N,N′,N″,N′″-tetracetic acid (TITRA) and its derivatives,
• vi) triethylenetetramine hexaacetic acid (TTHA) and its derivatives,
• vii) 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid (NODAGA) and its derivatives, and
• viii) 1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid (NODASA) and its derivatives, and
• L is a linker which separates X and Aa8, and said linker L is selected from the group consisting of
• -Aa6-Aa7-, wherein X is coupled to Aa6 via the ε-NH2 of the lateral chain of Aa6, or
• -L1-Aa6-Aa7-, wherein X is coupled to L1, and L1 is coupled to Aa6 via the ε-NH2 of the lateral chain of Aa6 or via the α-NH2 of Aa6,
• wherein
• Aa6 is selected from the group consisting of (D)Lys, and (L)Lys,
• Aa7 is selected from the group consisting of (L)Pro, and (D)Pro,
• and L1 is —NH—(CH2)n—CO— wherein n is from 1 to 5, and
• an acetyl group is coupled to the remaining NH2 of Aa6,
• and wherein
• said analogue, when in solution at physiological pH and at physiological temperature, has at most two positive charges.