AGREEMENT OF SUBSTITUTION AND AMENDMENT OF
                                RIGHTS AGREEMENT


     This Agreement of Substitution  and Amendment is entered into as of the 1st
day  of  September,  2004  by  and  between  Cytogen  Corporation,   a  Delaware
corporation  (the "Company") and American Stock Transfer & Trust Company,  a New
York banking corporation ("AST").

                                    RECITALS

A.   On or about  October  19,  1998,  the Company  entered  into an Amended and
     Restated  Rights  Agreement (the "Rights  Agreement")  with Mellon Investor
     Services  LLC,  formerly  ChaseMellon  Shareholder  Services,  L.L.C.  (the
     "Predecessor Agent") as rights agent.

B.   The Company  wishes to remove the  Predecessor  Agent and substitute AST as
     rights agent pursuant to Section 21 of the Rights Agreement.

C.   The  Company  has given the  Predecessor  Agent  notice of  removal  of the
     Predecessor Agent as rights agent.

                                    AGREEMENT

     NOW   THEREFORE,   in   consideration   of  the   foregoing  and  of  other
consideration,  the  sufficiency  of which is hereby  acknowledged,  the parties
agree as follows:

1.   Section 21 of the Rights  Agreement  is hereby  amended to provide that any
     successor  rights agent  shall,  at the time of its  appointment  as rights
     agent, have a combined capital  and surplus of at least $10 million, rather
     than $50 million.

2.   The Company  hereby  appoints AST as rights agent pursuant to Section 21 of
     the Rights  Agreement,  to serve in that capacity for the consideration and
     subject to all of the terms and conditions of the Rights Agreement.

3.   AST hereby  accepts the  appointment as rights agent pursuant to Section 21
     of the  Rights  Agreement  and  agrees  to serve in that  capacity  for the
     consideration  and subject to all of the terms and conditions of the Rights
     Agreement.



4.   From and after the effective date hereof,  each and every  reference in the
     Rights  Agreement to a "Rights  Agent" shall be deemed to be a reference to
     AST.

5.   Section 26 of the Rights  Agreement  is amended to provide  that notices or
     demands shall be addressed as follows (until another address is filed):

          If to the Company:

          Cytogen Corporation
          650 College Road East, Suite 3100
          Princeton, NJ 08540
          Attn:  Donald L. Novajosky, Esq.

          If to AST:

          American Stock Transfer & Trust Company
          59 Maiden Lane
          New York, NY 10038
          Attention:  Corporate Trust Department

6.   Except as expressly  modified herein,  the Rights Agreement shall remain in
     full force and effect.

7.   This Agreement of Substitution and Amendment may be executed in one or more
     counterparts,  each of which  shall  together  constitute  one and the same
     document.

                                 * * * * * * * *



     IN WITNESS  WHEREOF,  the parties  have caused  this  Agreement  to be duly
executed as of the date indicated above.


CYTOGEN CORPORATION                         AMERICAN STOCK TRANSFER
                                            & TRUST COMPANY



/s/ Michael D. Becker                       /s/ Herbert J. Lemmer
-------------------------------------       ------------------------------------
Michael D. Becker,                          Herbert J. Lemmer,
President and Chief Executive Officer       Vice President