Diagnostic agents for pancreatic exocrine function

Abstract

A diagnostic agent for pancreatic exocrine function comprising an amino acid or a peptide containing at least one 13 C or 14 C atom, or a pharmaceutically acceptable salt thereof other than Bz-Tyr- 13 C-PABA is provided. A 13 C- or 14 C-labeled compound represented by the following formula (II): X 2 —R 2 —Y 2 —Z 1   (II) or a salt thereof, wherein X 2 is a hydrogen atom or a protecting group, R 2 is a peptide of 2 to 5 amino acids, an amino acid or a single bond, Y 2 is an amino acid, Z 1 is an amino acid optionally having a protecting group, and at least one of the amino acids in R 2 , Y 2 and Z 1 , or at least one of the protecting groups in X 2 and Z 1 when the protecting groups contain a carbon atom, is 13 C or 14 C-labeled.

What is claimed is:  
     
         1 . A diagnostic agent for pancreatic exocrine function comprising an amino acid or a peptide containing at least one  13 C or  14 C atom, or a pharmaceutically acceptable salt thereof other than Bz-L-Tyr- 13 C-PABA.  
     
     
         2 . The diagnostic agent of  claim 1 , wherein the amino acid molecule contains a  13 C or  14 C atom.  
     
     
         3 . The diagnostic agent of  claim 1 , wherein the amino acid or peptide has a modifying or protecting group and the modifying or protecting group contains a  13 C or  14 C atom.  
     
     
         4 . The diagnostic agent of any one of claims  1 - 3 , wherein the amino acid or peptide is represented by the following formula (I): 
       X 1 —R 1 —Y 1   (I) 
       wherein X 1  is a hydrogen atom or a protecting group, R 1  is a peptide of 2 to 50 amino acids, an amino acid or a single bond, Y 1  is an amino acid optionally having a protecting group.  
     
     
         5 . The diagnostic agent of  claim 4 , wherein at least one of the amino acids in R 1  and Y 1 , or at least an ester group in Y 1  when the amino acid in Y 1  is protected with the ester group, is  13 C- or  14 C-labeled.  
     
     
         6 . The diagnostic agent of any one of claims  1 - 5 , wherein after the reaction of a protease or proteases, the amino acid or peptide, or pharmaceutically acceptable salt thereof is decarboxylated to generate  13 CO 2  or  14 CO 2 .  
     
     
         7 . The diagnostic agent of  claim 6 , wherein the protease or proteases are pancreatic exocrine proteases.  
     
     
         8 . The diagnostic agent of  claim 7 , wherein the pancreatic exocrine protease or proteases are selected from the group consisting of chymotrypsin, trypsin, elastase, and carboxypeptidases.  
     
     
         9 . The diagnostic agent of any one of claims  1 - 8 , which is used in a breath test.  
     
     
         10 . A 1 13 C- or  14 C-labeled compound represented by the following formula (II): 
       X 2 —R 2 —Y 2 —Z 1   (II) 
       or a salt thereof, 
 wherein X 2  is a hydrogen atom or a protecting group, R 2  is a peptide of 2 to 5 amino acids, an amino acid or a single bond, Y 2  is an amino acid, Z 1  is an amino acid optionally having a protecting group, and at least one of the amino acids in R 2 , Y 2  and Z 1 , or at least one of the protecting groups in X 2  and Z 1  when the protecting groups contain a carbon atom, is  13 C- or  14 C-labeled, provided that the following compounds are excluded:  
 L-Ala-L-Pro, L-Gly-L-Leu, L-Gly-L-Phe, L-Val-L-Leu, L-Leu-L-Leu, L-Tyr-L-Leu, Ac-D-Ala-D-Ala, L-Gly-L-Gly-OEt, L-Leu-L-Ala-OMe, Ac-L-Gly-L-Pro-OMe, Boc-L-Leu-L-Ala-OMe, L-Gly-L-Pro-L-Leu, L-Gly-L-Pro-L-Phe, L-Ala-L-Gly-L-Gly, L-Gly-L-Leu-L-Pro, L-Phe-L-Asp-L-Met, L-Gly-L-Leu-L-Pro, Dansyl-L-Tyr-L-Val-D-Ala, Cbz-L-Gly-L-Leu-L-Ala, L-Thr-L-Leu-L-Asn-Bzl, Z-L-Pro-L-Pro-L-Gly-OEt, L-Leu-L-Leu-L-Leu-L-Leu, L-Lys-L-Arg-L-Asp-L-Ser, Ac-L-Leu-L-Ala-L-Ala-L-Gln(NMe 2 ), Ac-L-Leu-L-Ala-L-Ala-L-Gln(NMe 2 )-SEt, L-Tyr-L-Gly-L-Gly-L-Phe-L-Leu and L-Tyr-L-Gly-L-Gly-L-Phe-L-Met, wherein Ac is acetyl, Et is ethyl, Me is methyl, Boc is t-butyloxycarbonyl, Cbz is carbobenzyloxy, Bzl is benzoyl, Z is benzyloxycarbonyl, SEt is ethanethiol, and NMe 2  is dimethylamino.  
 
     
     
         11 . The  13 C- or  14 C-labeled compound, or salt thereof of  claim 10 , wherein 
 1) in the case where X 2  is a protecting group and R 2  is a single bond, 
 1-i) when Z 1  is D-Ala, Y 2  is an amino acid other than D-Ala,  
 1-ii) when Z 1  is L-Ala-OMe, Y 2  is an amino acid other than L-Leu,  
 1-iii) when Z 1  is L-Pro-OMe, Y 2  is an amino acid other than L-Gly,  
   2) in the case where X 2  is a protecting group and R 2  is an amino acid, 
 2-i) when Z 1  is D-Ala, Y 2  is an amino acid other than L-Val,  
 2-ii) when Z 1  is L-Ala, Y 2  is an amino acid other than L-Leu,  
 2-iii) when Z 1  is L-Gly-OEt, Y 2  is an amino acid other than L-Pro,  
   3) in the case where X 2  is a protecting group, R 2  is a peptide of 2 amino acids and Z 1  is L-Gln optionally having SEt, Y 2  is an amino acid other than L-Ala,    4) in the case where X 2  is a hydrogen atom and R 2  is a single bond, 
 4-i) when Z 1  is L-Pro, Y 2  is an amino acid other than L-Ala,  
 4-ii) when Z 1  is L-Leu, Y 2  is an amino acid other than L-Gly, L-Val, L-Leu and L-Tyr,  
 4-iii) when Z 1  is L-Phe, Y 2  is an amino acid other than L-Gly,  
 4-iv) when Z 1  is L-Gly-OEt, Y 2  is an amino acid other than L-Gly,  
 4-v) when Z 1  is L-Ala-OMe, Y 2  is an amino acid other than L-Leu,  
   5) in the case where X 2  is a hydrogen atom and R 2  is an amino acid, 
 5-i) when Z 1  is L-Leu, Y 2  is an amino acid other than L-Pro,  
 5-ii) when Z 1  is L-Phe, Y 2  is an amino acid other than L-Pro,  
 5-iii) when Z 1  is L-Gly, Y 2  is an amino acid other than L-Gly,  
 5-iv) when Z 1  is L-Pro, Y 2  is an amino acid other than L-Leu,  
 5-v) when Z 1  is L-Met, Y 2  is an amino acid other than L-Asp,  
 5-vi) when Z 1  is L-Asn-Bzl, Y 2  is an amino acid other than L-Leu,  
   6) in the case where X 2  is a hydrogen atom and R 2  is a peptide of 2 amino acids, 
 6-i) when Z 1  is L-Leu, Y 2  is an amino acid other than L-Leu,  
 6-ii) when Z 1  is L-Ser, Y 2  is an amino acid other than L-Asp, and  
   7) in the case where X 2  is a hydrogen atom and R 2  is a peptide of 3 amino acids, 
 7-i) when Z 1  is L-Leu, Y 2  is an amino acid other than L-Phe,  
 7-ii) when Z 1  is L-Met, Y 2  is an amino acid other than L-Phe.  
   
     
     
         12 . The  13 C- or  14 C-labeled compound, or salt thereof of  claim 10  or  11 , wherein 
 1) in the case where X 2  is a protecting group selected from the group consisting of Dansyl, Cbz, Ac and Z, and R 2  is an amino acid or a peptide of 2 amino acids, 
 1-i) when Z 1  is D-Ala, Y 2  is an amino acid other than L-Val,  
 1-ii) when Z 1  is L-Ala, Y 2  is an amino acid other than L-Leu,  
 1-iii) when Z 1  is L-Gly-OEt, Y 2  is an amino acid other than L-Pro,  
 1-iv) when Z 1  is L-Gln(NMe 2 ) or L-Gln(NMe 2 )-SEt, Y 2  is an amino acid other than L-Ala,  
 
 2) in the case where X 2  is Ac or Boc, and R 2  is a single bond, 
 2-i) when Z 1  is D-Ala, Y 2  is an amino acid other than D-Ala,  
 2-ii) when Z 1  is L-Pro-OMe, Y 2  is an amino acid other than L-Gly,  
 2-iii) when Z 1  is L-Ala-OMe, Y 2  is an amino acid other than L-Leu,  
 
 3) in the case where X 2  is a hydrogen atom and R 2  is an amino acid or a peptide of 2 or 3 amino acids, 
 3-i) when Z 1  is L-Leu, Y 2  is an amino acid other than L-Pro, L-Leu and L-Phe,  
 3-ii) when Z 1  is L-Phe, Y 2  is an amino acid other than L-Pro,  
 3-iii) when Z 1  is L-Gly, Y 2  is an amino acid other than L-Gly,  
 3-iv) when Z 1  is L-Pro, Y 2  is an amino acid other than L-Leu,  
 3-v) when Z 1  is L-Met, Y 2  is an amino acid other than L-Asp and L-Phe,  
 3-vi) when Z 1  is L-Asn-Bzl, Y 2  is an amino acid other than L-Leu,  
 3-vii) when Z 1  is L-Ser, Y 2  is an amino acid other than L-Asp, and  
 
 4) in the case where X 2  is a hydrogen atom and R 2  is a single bond, 
 4-i) when Z 1  is L-Pro, Y 2  is an amino acid other than L-Ala,  
 4-ii) when Z 1  is L-Leu, Y 2  is an amino acid other than L-Gly, L-Val, L-Leu and L-Tyr,  
 4-iii) when Z 1  is L-Phe, Y 2  is an amino acid other than L-Gly,  
 4-iv) when Z 1  is L-Gly-OEt, Y 2  is an amino acid other than L-Gly,  
 4-v) when Z 1  is L-Ala-OMe, Y 2  is an amino acid other than L-Leu.  
 
 
     
     
         13 . The  13 C- or  14 C-labeled compound or salt thereof of any one of claims  10 - 12 , wherein X 2  is selected from the group consisting of Ac, Bz (benzoyl), Boc, Z and a hydrogen atom.  
     
     
         14 . The  13 C- or  13 C-labeled compound or salt thereof of any one of claims  10 - 13 , wherein after the reaction of a protease or proteases, the amino acid or peptide, or salt thereof is decarboxylated to generate  13 CO2 or  14 CO 2 .  
     
     
         15 . The  13 C- or  14 C-labeled compound or salt thereof of  claim 14 , wherein the protease or proteases are pancreatic exocrine proteases.  
     
     
         16 . The  13 C- or  14 C-labeled compound or salt thereof of  claim 15 , wherein the pancreatic exocrine protease or proteases are selected from the group consisting of chymotrypsin, trypsin, elastase, and carboxypeptidases.  
     
     
         17 . The  13 C- or  14 C-labeled compound or salt thereof of any one of claims  10 - 16 , wherein X 2  is a protecting group and R 2  is a single bond.  
     
     
         18 . The  13 C- or  14 C-labeled compound or salt thereof of any one of claims  10 - 17 , wherein 
 (1) at least one of the amino acids in Y 2  and Z 1  is Arg or Lys,    (2) at least one of the amino acids in Y 2  and Z 1  is an aromatic amino acid, Leu, His or Met,    (3) at least one of the amino acids in Y 2  and Z 1  is a neutral and non-aromatic amino acid,    (4) the amino acid in Z 1  is an amino acid other than Arg, Lys and Pro, or    (5) the amino acid in Z 1  is Arg or Lys.    
     
     
         19 . The  13 C- or  14 C-labeled compound or salt thereof of any one of claims  10 - 18 , wherein X 2  is selected from the group consisting of a hydrogen atom, Bz, Ac and Boc, Y 2  is selected from the group consisting of Phe, Ala, Gly, Tyr and Arg, and Z 1  is selected from the group consisting of Leu optionally having a protecting group, Ala optionally having a protecting group, and Gly optionally having a protecting group.  
     
     
         20 . The  13 C- or  14 C-labeled compound or salt thereof of  claim 19 , wherein Z 1  is selected from the group consisting of Leu, Ala, Gly, Leu-OMe, Leu-OEt, Ala-OMe, Ala-OEt, Gly-OMe and Gly-OEt.  
     
     
         21 . The  13 C- or  14 C-labeled compound or salt thereof of any one of claims  10 - 20 , wherein Z 1  is a  13 C- or  14 C-labeled amino acid optionally having a protecting group.  
     
     
         22 . The  13 C- or  14 C-labeled compound or salt thereof of  claim 10 , which is selected from the group consisting of the following compounds: 
 (a) Phe- 13 C-Leu,    (b) Arg- 13 C-Leu    (c) Bz-Ala- 13 C-Ala,    (d) Bz-Gly- 13 C-Leu,    (e) Bz-Phe- 13 C-Gly,    (f) Bz-Tyr- 13 C-Leu,    (g) Bz-Phe- 13 C-Leu,    (h) Bz-(DL)Phe- 13 C-Leu,    (j) Bz-Arg- 13 C-Leu,    (k) Ac-Phe- 13 C-Leu,    (l) Ac-Tyr- 13 C-Leu,    (m) Bz-Ala- 13 C-Ala-OMe,    (n) Bz-Gly- 13 C-Leu-OMe,    (o) Bz-Phe- 13 C-Gly-OMe,    (p) Bz-Phe- 13 C-Leu-OMe,    (q) Bz-(DL)Phe- 13 C-Leu-OMe,    (r) Ac-Phe- 13 C-Leu-OMe,    (s) Ac-Tyr- 13 C-Leu-OMe,    (t) Bz-Ala-Ala-Ala-Ala-Gly-Phe- 13 C-Leu,    (u) Boc-Ala-Ala-Ala-Ala-Gly-Phe- 13 C-Leu, and    (v) Bz-Ala-Ala-Ala-Ala- 13 C-Gly-Phe-Leu.    
     
     
         23 . A diagnostic agent for pancreatic exocrine function comprising an amino acid or a peptide containing at least one  13 C or  14 C atom, or a pharmaceutically acceptable salt thereof other than Bz-L-Tyr- 13 C-PABA, wherein said amino acid or all amino acids constituting said peptide is (are) an L-isomer(s).  
     
     
         24 . A  13 C- or  14 C-labeled compound represented by the following formula (IIa): 
       X 2a —R 2a —Y 2a —Z 1a   (IIa) 
       or a salt thereof, wherein all amino acids constituting the labeled compound are L-isomers, 
 wherein X 2a  is a hydrogen atom or a protecting group, R 2a  is a peptide of 2 to 5 amino acids, an amino acid or a single bond, Y 2a  is an amino acid, Z 1a  is an amino acid optionally having a protecting group, and at least one of the amino acids in R 2a , Y 2a  and Z 1a , or at least one of the protecting groups in X 2a  and Z 1a  when the protecting groups contain a carbon atom, is  13 C- or  14 C-labeled, provided that the following compounds are excluded from the compounds represented by the formula (IIa):  
 L-Ala-L-Pro, L-Gly-L-Leu, L-Gly-L-Phe, L-Val-L-Leu, L-Leu-L-Leu, L-Tyr-L-Leu, L-Gly-L-Gly-OEt, L-Leu-L-Ala-OMe, Ac-L-Gly-L-Pro-OMe, Boc-L-Leu-L-Ala-OMe, L-Gly-L-Pro-L-Leu, L-Gly-L-Pro-L-Phe, L-Ala-L-Gly-L-Gly, L-Gly-L-Leu-L-Pro, L-Phe-L-Asp-L-Met, L-Gly-L-Leu-L-Pro, Cbz-L-Gly-L-Leu-L-Ala, L-Thr-L-Leu-L-Asn-Bzl, Z-L-Pro-L-Pro-L-Gly-OEt, L-Leu-L-Leu-L-Leu-L-Leu, L-Lys-L-Arg-L-Asp-L-Ser, Ac-L-Leu-L-Ala-L-Ala-L-Gln(NMe 2 ), Ac-L-Leu-L-Ala-L-Ala-L-Gln(NMe 2 )-SEt, L-Tyr-L-Gly-L-Gly-L-Phe-L-Leu and L-Tyr-L-Gly-L-Gly-L-Phe-L-Met, wherein Ac is acetyl, Et is ethyl, Me is methyl, Boc is t-butyloxycarbonyl, Cbz is carbobenzyloxy, Bzl is benzoyl, Z is benzyloxycarbonyl, SEt is ethanethiol, and NMe 2  is dimeth ylamino.  
 
     
     
         25 . The  13 C- or  14 C-labeled compound, or salt thereof of  claim 24 , wherein 
 1) in the case where X 2a  is a protecting group and R 2a  is a single bond, 
 1-i) when Z 1a  is L-Ala-OMe, Y 2a  is an amino acid other than L-Leu,  
 1-ii) when Z 1a  is L-Pro-OMe, Y 2a  is an amino acid other than L-Gly,  
 2) in the case where X 2a  is a protecting group and R 2a  is an amino acid,  
 2-i) when Z 1a  is L-Ala, Y 2a  is an amino acid other than L-Leu,  
 2-ii) when Z 1a  is L-Gly-OEt, Y 2a  is an amino acid other than L-Pro,  
 3) in the case where X 2a  is a protecting group, R 2a  is a peptide of 2 amino acids and Z 1a  is L-Gln optionally having SEt, Y 2a  is an amino acid other than L-Ala,  
   4) in the case where X 2a  is a hydrogen atom and R 2a  is a single bond, 
 4-i) when Z 1a  is L-Pro, Y 2a  is an amino acid other than L-Ala,  
 4-ii) when Z 1a  is L-Leu, Y 2  is an amino acid other than L-Gly, L-Val, L-Leu and L-Tyr,  
 4-iii) when Z 1a  is L-Phe, Y 2a  is an amino acid other than L-Gly,  
 4-iv) when Z 1a  is L-Gly-OEt, Y 2a  is an amino acid other than L-Gly,  
 4-v) when Z 1a  is L-Ala-OMe, Y 2a  is an amino acid other than L-Leu,  
   5) in the case where X 2a  is a hydrogen atom and R 2a  is an amino acid, 
 5-i) when Z 1a  is L-Leu, Y 2a  is an amino acid other than L-Pro,  
 5-ii) when Z 1a  is L-Phe, Y 2a  is an amino acid other than L-Pro,  
 5-iii) when Z 1a  is L-Gly, Y 2a  is an amino acid other than L-Gly,  
 5-iv) when Z 1a  is L-Pro, Y 2a  is an amino acid other than L-Leu,  
 5-v) when Z 1a  is L-Met, Y 2a  is an amino acid other than L-Asp,  
 5-vi) when Z 1a  is L-Asn-Bzl, Y 2a  is an amino acid other than L-Leu,  
   6) in the case where X 2a  is a hydrogen atom and R 2a  is a peptide of 2 amino acids, 
 6-i) when Z 1  is L-Leu, Y 2a  is an amino acid other than L-Leu,  
 6-ii) when Z 1a  is L-Ser, Y 2a  is an amino acid other than L-Asp, and  
   7) in the case where X 2a  is a hydrogen atom and R 2a  is a peptide of 3 amino acids, 
 7-i) when Z 1a  is L-Leu, Y 2a  is an amino acid other than L-Phe,  
 7-ii) when Z 1a  is L-Met, Y 2a  is an amino acid other than L-Phe.  
   
     
     
         26 . The  13 C- or  14 C-labeled compound, or salt thereof of  claim 24  or  25 , wherein 
 1) in the case where X 2a  is a protecting group selected from the group consisting of Cbz, Ac and Z, and R 2a  is an amino acid or a peptide of 2 amino acids, 
 1-i) when Z 1a  is L-Ala, Y 2  is an amino acid other than L-Leu,  
 1-ii) when Z 1a  is L-Gly-OEt, Y 2a  is an amino acid other than L-Pro,  
 1-iii) when Z 1a  is L-Gln(NMe 2 ) or L-Gln(NMe 2 )-SEt, Y 2a  is an amino acid other than L-Ala,  
 
 2) in the case where X 2a  is Ac or Boc, and R 2a  is a single bond, 
 2-i) when Z 1a  is L-Pro-OMe, Y 2a  is an amino acid other than L-Gly,  
 2-ii) when Z 1  is L-Ala-OMe, Y 2a  is an amino acid other than L-Leu,  
 
 3) in the case where X 2a  is a hydrogen atom and R 2a  is an amino acid or a peptide of 2 or 3 amino acids, 
 3-i) when Z 1a  is L-Leu, Y 2a  is an amino acid other than L-Pro, L-Leu and L-Phe,  
 3-ii) when Z 1a  is L-Phe, Y 2a  is an amino acid other than L-Pro,  
 3-iii) when Z 1a  is L-Gly, Y 2a  is an amino acid other than L-Gly,  
 3-iv) when Z 1a  is L-Pro, Y 2a  is an amino acid other than L-Leu,  
 3-v) when Z 1a  is L-Met, Y 2a  is an amino acid other than L-Asp and L-Phe,  
 3-vi) when Z 1  is L-Asn-Bzl, Y 2a  is an amino acid other than L-Leu,  
 3-vii) when Z 1a  is L-Ser, Y 2a  is an amino acid other than L-Asp, and  
 
 4) in the case where X 2a  is a hydrogen atom and R 2a  is a single bond, 
 4-i) when Z 1a  is L-Pro, Y 2a  is an amino acid other than L-Ala,  
 4-ii) when Z 1a  is L-Leu, Y 2a  is an amino acid other than L-Gly, L-Val, L-Leu and L-Tyr,  
 4-iii) when Z 1a  is L-Phe, Y 2a  is an amino acid other than L-Gly,  
 4-iv) when Z 1a  is L-Gly-OEt, Y 2a  is an amino acid other than L-Gly,  
 4-v) when Z 1a  is L-Ala-OMe, Y 2a  is an amino acid other than L-Leu.  
 
 
     
     
         27 . The  1 C- or  14 C-labeled compound or salt thereof of any one of claims  24 -26, wherein X 2a  is selected from the group consisting of Ac, Bz (benzoyl), Boc, Z and a hydrogen atom.  
     
     
         28 . The  1 C- or  14 C-labeled compound or salt thereof of any one of claims  24 - 27  wherein X 2a  is a protecting group and R 2a  is a single bond.  
     
     
         29 . The  13 C- or  14 C-labeled compound or salt thereof of any one of claims  24 - 28 , wherein 
 (1) at least one of the amino acids in Y 2a  and Z 1a  is L-Arg or L-Lys,    (2) at least one of the amino acids in Y 2a  and Z 1a  is an aromatic L-amino acid, L-Leu, L-His or L-Met,    (3) at least one of the amino acids in Y 2a  and Z 1a  is a neutral and non-aromatic L-amino acid,    (4) the amino acid in Z 1a  is an L-amino acid other than L-Arg, L-Lys and L-Pro, or    (5) the amino acid in Z 1a  is L-Arg or L-Lys.    
     
     
         30 . The  13 C- or  14 C-labeled compound or salt thereof of any one of claims  24 - 29 , wherein X 2a  is selected from the group consisting of a hydrogen atom, Bz, Ac and Boc, Y 2a  is selected from the group consisting of L-Phe, L-Ala, L-Gly, L-Tyr and L-Arg, and Z 1a  is selected from the group consisting of L-Leu optionally having a protecting group, L-Ala optionally having a protecting group, and L-Gly optionally having a protecting group.  
     
     
         31 . The  13 C- or  14 C-labeled compound or salt thereof of  claim 30 , wherein Z 1a  is selected from the group consisting of L-Leu, L-Ala, L-Gly, L-Leu-OMe, L-Leu-OEt, L-Ala-OMe, L-Ala-OEt, L-Gly-OMe and L-Gly-OEt.  
     
     
         32 . The  13 C- or  14 C-labeled compound or salt thereof of any one of claims  24 - 31 , wherein Z 1a  is a  13 C- or  14 C-labeled amino acid optionally having a protecting group.  
     
     
         33 . The  13 C- or  14 C-labeled compound or salt thereof of  claim 24 , which is selected from the group consisting of the following compounds: 
 (a) L-Phe- 13 C-L-Leu,    (b) L-Arg- 13 C-L-Leu,    (c) Bz-L-Ala- 13 C-L-Ala,    (d) Bz-L-Gly- 13 C-L-Leu,    (e) Bz-L-Phe- 13 C-L-Gly,    (f) Bz-L-Tyr- 13 C-L-Leu,    (g) Bz-L-Phe- 13 C-L-Leu,    (h) Bz-L-Arg- 13 C-L-Leu,    (i) Ac-L-Phe- 13 C-L-Leu,    (j) Ac-L-Tyr- 13 C-L-Leu,    (k) Bz-L-Ala- 13 C-L-Ala-OMe,    (l) Bz-L-Gly- 13 C-L-Leu-OMe,    (m) Bz-L-Phe- 13 C-L-Gly-OMe,    (n) Bz-L-Phe- 13 C-L-Leu-OMe,    (o) Ac-L-Phe- 13 C-L-Leu-OMe,    (p) Ac-L-Tyr- 13 C-L-Leu-OMe,    (q) Bz-L-Ala-L-Ala-L-Ala-L-Ala-L-Gly-L-Phe- 13 C-L-Leu,    (r) Boc-L-Ala-L-Ala-L-Ala-L-Ala-L-Gly-L-Phe- 13 C-L-Leu, and    (s) Bz-L-Ala-L-Ala-L-Ala-L-Ala- 13 C-L-Gly-L-Phe-L-Leu.    
     
     
         34 . A diagnostic agent for pancreatic exocrine function comprising an amino acid or a peptide containing at least one  13 C- or  14 C atom, or a pharmaceutically acceptable salt thereof, wherein at least one of said amino acid or amino acids constituting said peptide is a D-isomer or a DL-mixture.  
     
     
         35 . A  13 C- or  14 C-labeled compound represented by the following formula (IIb): 
       X 2a —R 2b —Z 1b   (IIb) 
       or a salt thereof, wherein at least one of amino acids constituting the labeled compound is a D-isomer or a DL-mixture, 
 wherein X 2b  is a hydrogen atom or a protecting group, R 2b  is a peptide of 2 to 5 amino acids, an amino acid or a single bond, Y 2b  is an amino acid, Z 1b  is an amino acid optionally having a protecting group, and at least one of the amino acids in R 2b , Y 2b  and Z 1b , or at least one of the protecting groups in X 2b  and Z 1b  when the protecting groups contain a carbon atom, is  13 C- or  14 C-labeled, provided that the following compounds are excluded from the compounds represented by the formula (IIb):  
 Ac-D-Ala-D-Ala and Dansyl-L-Tyr-L-Val-D-Ala, wherein Ac is acetyl.  
 
     
     
         36 . The  13 C- or  1 4C-labeled compound, or salt thereof of  claim 35 , wherein 
 1) in the case where X 2b  is a protecting group and R 2b  is a single bond, when Z 1b  is D-Ala, Y 2b  is an amino acid other than D-Ala,    2) in the case where X 2b  is a protecting group and R 2b  is an amino acid, when Z 1b  is D-Ala, Y 2b  is an amino acid other than Val.    
     
     
         37 . The  13 C- or  14 C-labeled compound or salt thereof of any one of claims  35 - 36 , wherein X 2b  is selected from the group consisting of Ac, Bz (benzoyl), Boc, Z and a hydrogen atom.  
     
     
         38 . The  13 C- or  14 C-labeled compound or salt thereof of any one of claims  35 - 37 , wherein X 2b  is a protecting group and R 2b  is a single bond.  
     
     
         39 . The  13 C- or  14 C-labeled compound or salt thereof of any one of claims  35 - 38 , wherein 
 (1) at least one of the amino acids in Y 2a  and Z 1b  is Arg or Lys,    (2) at least one of the amino acids in Y 2b  and Z 1b  is an aromatic amino acid, Leu, His or Met,    (3) at least one of the amino acids in Y 2b  and Z 1b  is a neutral and non-aromatic amino acid,    (4) the amino acid in Z 1b  is an amino acid other than Arg, Lys and Pro, or    (5) the amino acid in Z 1b  is Arg or Lys.    
     
     
         40 . The  13 C- or  14 C-labeled compound or salt thereof of any one of claims  35 - 39 , wherein X 2b  is selected from the group consisting of a hydrogen atom, Bz, Ac and Boc, Y 2b  is selected from the group consisting of Phe, Ala, Gly, Tyr and Arg, and Z 1b  is selected from the group consisting of Leu optionally having a protecting group, Ala optionally having a protecting group, and Gly optionally having a protecting group.  
     
     
         41 . The  13 C- or  14 C-labeled compound or salt thereof of  claim 40 , wherein Z 1b  is selected from the group consisting of Leu, Ala, Gly, Leu-OMe, Leu-OEt, Ala-OMe, Ala-OEt, Gly-OMe and Gly-OEt.  
     
     
         42 . The  13 C- or  14 C-labeled compound or salt thereof of any one of claims  35 - 41 , wherein Z 1b  is a  13 C- or  14 C-labeled amino acid optionally having a protecting group.  
     
     
         43 . The  13 C- or  14 C-labeled compound or salt thereof of  claim 35 , which is selected from the group consisting of the following compounds: 
 (a) Phe- 13 C-Leu,    (b) Arg- 13 C-Leu,    (c) Bz-Ala- 13 C-Ala,    (d) Bz-Gly- 13 C-Leu,    (e) Bz-Phe- 13 C-Gly,    (f) Bz-Tyr  13 C-Leu,    (g) Bz-Phe- 13 C-Leu,    (h) Bz-(DL)Phe- 13 C-Leu,    (j) Bz-Arg- 13 C-Leu,    (k) Ac-Phe- 13 C-Leu,    (l) Ac-Tyr- 13 C-Leu,    (m) Bz-Ala- 13 C-Ala-OMe,    (n) Bz-Gly- 13 C-Leu-OMe,    (o) Bz-Phe- 13 C-Gly-OMe,    (p) Bz-Phe- 13 C-Leu-OMe,    (q) Bz-(DL)Phe- 13 C-Leu-OMe,    (r) Ac-Phe- 13 C-Leu-OMe,    (s) Ac-Tyr- 13 C-Leu-OMe,    (t) Bz-Ala-Ala-Ala-Ala-Gly-Phe- 13 C-Leu,    (u) Boc-Ala-Ala-Ala-Ala-Gly-Phe- 13 C-Leu, and    (v) Bz-Ala-Ala-Ala-Ala- 13 C-Gly-Phe-Leu.