Imaging Tumors in Humans with Tc‐99m‐VIP

Abstract

A BSTRACT : Vasoactive intestinal peptide (VIP) was modified at the C terminus with a spacer and four amino acids to serve as a chelating moiety. The modified peptide, TP 3654, was labeled with Tc-99m and evaluated in normal volunteers, as well as in patients with a history of cancer. Renal clearance (67%) was the primary route of excretion, with approximately 20% of the radioactivity clearing through the hepatobiliary system. No adverse reaction was noted in any of the subjects and all, except one small, of the known lesions as seen by CT, MRI, Tc-99m-MIBI, or mammography were correctly identified within a few minutes of an i.v. injection of approximately 10 mCi of Tc-99m-TP 3654 (specific activity 11.3 ؋ 10 3 Ci/m mol). The scans were in concordance in nine patients. In the remaining two, one with a visible mass in the neck from high grade spindle cell sarcoma and the other with a palpable mass in a breast from ductal epithelial hyperplasia, were localized only with Tc-99m-TP 3654, but not with Tc-99m-MIBI. Both malignancies are known to express VIP receptors. The VIP analog promises to be a nontoxic and reliable agent for imaging cancers in humans that express VIP receptors.

In vitro and in vivo Evaluation of 111In-labeled E. coli Heat-Stable Enterotoxin Analogs for Specific Targeting of Human Breast Cancers

“…For the synthesis of 111 In-DOTA-Phe 19 -ST h (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), an aliquot of 111 InCl 3 (0.5-2.5 mCi, 1.85-9.25 MBq, 50 ll) was added to a solution of DOTA-Phe 19 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) conjugate was concentrated by passage through a 3 M Empore C-18 HD high performance extraction disk (7 mm/3 ml) cartridge and eluting with 33% ethanol in 0.1 M NaH 2 PO 4 buffer (400 ll). The concentrated fraction was diluted with 0.1 M NaH 2 PO 4 buffer (2-3 ml, pH 7) to make the final concentration of ethanol in the solution <5%.…”

“…0.2 mg DOTA-F 19 -ST h (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) in 100 ll 0.4 M ammonium acetate, pH 6.0, was added to 100 lg indium chloride. Reactions were incubated at 80°C for 1 h. The resulting indium complex was purified by RP-HPLC and analyzed by ESI-MS (Synpep Corp., Dublin, CA).…”

“…Receptors for several different peptides are expressed in breast cancers, including receptors for somatostatin, vasoactive intestinal peptide (VIP), and the gastrinreleasing peptide (GRP) [8]. All of these peptides have been investigated as potential in vivo imaging agents for breast cancer [9][10][11][12][13][14]. Improved ability to determine the location and extent of metastatic disease using such agents could have a significant impact on treatment planning for individuals with confirmed diagnoses of primary tumors.…”

Development of Simplified Vasoactive Intestinal Peptide Analogs with Receptor Selectivity and Stability for Human Vasoactive Intestinal Peptide/Pituitary Adenylate Cyclase-Activating Polypeptide Receptors

“…However, [Ala 2,8,9,16,19,24,25 ]VIP (analog 8) had high affinity and potency for both VPAC subtypes and was much more metabolically stable than VIP in cells containing each VPAC subtype. These simplified, metabolically stable analogs should be useful for investigating the role of VPAC 1 in biological and pathological processes, for enhanced imaging of tumors overexpressing VIP receptors using VIP receptor scintigraphy (Virgolini, 1997;Thakur et al, 2000Thakur et al, , 2004Rao et al, 2001;Bhargava et al, 2002) as well as for possible VIP receptordirected antitumor treatment for tumors overexpressing VPACs (Gotthardt et al, 2004;Moody et al, 2004;Ou et al, 2005).…”

Evaluation of a PACAP Peptide Analogue Labeled with 68Ga Using Two Different Chelating Agents

“…15 In the past few years, this laboratory has designed, synthesized, and radiolabeled peptide conjugates that have high affinity for VPAC1 receptors, overexpressed in many malignant tumors, including those of the breast and prostate. [16][17][18][19][20] The peptides are analogues of pituitary adenylate cyclase-activating peptide (PACAP)-a 27 amino acid peptide and vasoactive intestinal peptide (VIP)-28 amino acid. Both have similar biochemical properties and bind to VPAC1 receptors expressed in high density on the surface of certain cancers such as of the breast, prostate, and urinary bladder (100%), colon (96%), pancreas (65%), lung (58%), stomach (54%), and liver (49%).…”