National Cancer Institute, Research Contracts Branch, PSAS, 6120 Executive Blvd, EPS/Room 638, Bethesda, MD 20892-7227

66 -- OVERHAUSER ENHANCED MAGNETIC RESONANCE IMAGING (OMRI) SOL RFQ-NCI-90109 DUE 060799 POC Todd Cole, Contracting Officer This is a combined synopsis/solicitation for commercial items, prepared in accordance with the format in FAR 12.6, as supplemented with additional information included in this notice. This announcement constitutes the only solicitation and a separate solicitation will not be issued. This solicitation, No. RFQ-NCI-90109 includes applicable provisions and clauses in effect through FAR FAC 97-11. The acquisition is being made in accordance with the test program for using simplified procedures for certain commercial items authorized in FAR 13.5. The solicitation is not set-aside for small businesses. BACKGROUND: The Radiation Biology Branch, Division of Clinical Sciences, National Cancer Institute has a research interest in the treatment of malignant tumors by non-surgical modalities, like radiation or chemotherapy, which may be influenced both by the genetic properties of the tumor cells and epigenetic factors of the tumor micromilieu . While extensive research is presently ongoing to develop gene therapy strategies targeted to tumor cells, the development of therapeutic regimens to exploit the physiological differences between normal and malignant tissue might also provide options for improved treatment. Some of the physiological differences between normal tissue and tumors include oxygen status, redox status, and intracellular pH. These differences, at least in part, can result from the physical architecture of the tumors with compromised blood supply. Methods that can detect subtle differences in the above physiological parameters would greatly aid in devising appropriate treatment strategies. Redox status and tissue pO2 are two factors which are hypothesized to be different in normal and malignant tissues. Techniques which enable rapid and noninvasive measurements of these two parameters in individual patients, therefore, would extend our knowledge and clinical acumen. The proposed research involves the use of Overhauser enhanced Magnetic Resonance Imaging (OMRI) to obtain functional/physiologic information in tumors using which treatment regimens will be adjusted depending on the oxygen status of the tumors and appropriate therapies can be instituted. In OMRI, an agent is infused prior to the imaging procedure, the infusion of the agent results in an enhancement of the proton images in the MRI performed at the low field (10 mT). The enhancement of the proton MRI depends on several factors, most important of which is the tissue pO2. Another unique feature of this technique is that the enhancement of the proton images is dependent inversely on the tissue pO2; lower the pO2, better the enhancement. Hence this technique is a hypoxia specific imaging technique, particularly in the regions of low oxygenation or ischemic regions as would be expected in pathologic conditions such as tumor hypoxia, infracted areas resulting from cardiovascular occlusion etc. The specific goals of this effort are to: evaluate OMRI as a means of determining tissue oxygen levels and compare its performance with EPR imaging; using a variety of animal tumor models, evaluate OMRI against other techniques for oxygen tissue measurements (EPRI, oxygen electrodes, immunohistochemical assays); monitor oxygen levels in murine tumors by OMRI during fractionated radiation treatment to determine if reoxygenation of hypoxic regions in tumors occurs and OMRI will be used to access the influence of systemic vasodilators such as nitric oxide donor agents on tumor oxygenation REQUIREMENTS: The following specifications are applicable to the OMRI: Scanner Control: NMR waveform generator -- digital, DDS-based; Waveform -- free programmable; Resolution -- 12 bit; Programmable attenuator -- 0-63 dB; Settling time of RF DAC -- 35 ns; ESR waveform generator -- PTS 500; Waveform -- block (on/off); Gradient/B0 waveform generator -- digital, DSP-based; DAC resolution -- 16 bit; DAC settling time -- 12 microsec. Data acquisition: Number of receive channels -- 2 (max 6); Frequency range analogue part -- 0.05 -- 2 MHz; Programmable attenuator -- 0-63 dB; ADC blank switch -- solid state; Passive blanking diodes -- matched to RF coil blank circuitry; A/D converter resolution -- 14 bit; Sample frequency -- 10 MHz; Bandwidth per pixel range -- 5 -- 1000Hz. Reconstruction: DSP-based reconstructor -- one per channel; Maximum matrix size -- 1024x1024 pixel. Host computer: CPU -- Pentium II, 200 MHz; Operating System -- SUSE Linux. For Overhauser enhanced MRI (OMRI), species with unpaired electrons are necessary to provide enhancement of the proton NMR signal intensities. The naturally occurring paramagnetic species are either not at sufficient levels or in some cases not suitable to provide the necessary enhancement factors for the practical implementation of OMRI. Therefore, to perform OMRI on live objects and also obtain physiologic information, exogenous contrast agents are mandatory. There are several potential agents which are candidates for OMRI as contrastagents. Though there are several contrast agents which can be used for OMRI, very few are suitable for medical imaging because of concerns related to radiation safety. Some of these agents were found to be well suited for EPR imaging studies, they have been used in NCI studies since 1993. NYCOMED Innovations has synthesized a series of contrast agents which meet all of the NCI requirements (Magnetic Resonance in Medicine Volume 38, pages 409-414 (1997). The characteristics of those agents are listed below: Narrow EPR spectrum -- With acceptable RF power deposition and minimal concerns related to biosafety of excess RF, contrast agents with narrow line widths provide superior enhancement factors for a given RF power; 2) Single line EPR spectrum -- Contrast agents with single line EPR spectrum will utilize the incident RF energy more efficiently than contrast agents with multiple spectral lines; 3) High relaxivity -- To limit the in vivo concentration of the contrast agent to obtain acceptable Overhauser enhancement, high relaxivity (> 2 s-1 mM-1) is necessary; 4) Water soluble: Water soluble contrast agents are desirable so as to administer concentrated solutions; 5) Bio stable -- The contrast agent should not be metabolized or excreted during the OMRI scanning procedure. However, metabolism after this procedure (2 h) is desirable; 6) Protein interaction -- The contrast agent should have minimal interaction with proteins so that they retain optimal Overhauser enhancement factors 7) Oxygen sensitivity -- The contrast agent should not chemically react with oxygen; however, the EPR spectral line widths should be physically modulated by oxygen; and 9) Limited self broadening -- At high concentrations, the self broadening of the EPR lines of the contrast agent should be minimal. EVALUATION CRITERIA: The Phillips Medical Systems OMRI is the only system known to the NCI which has been evaluated using contrast agents from NYCOMED Innovations, Sweden. The spectroscopic and pharmacologic data obtained from OMRI studies using the contrast agents were utilized to minimize the SAR and obtain enhancement factors appropriate for physiological imaging in large living objects. However, this is not documented and the purpose of this announcement is to determine if others qualify. Therefore, competitive proposals may be submitted for evaluation. The technical portion of quotations will receive paramount consideration in selecting a vendor. However, price will also be a significant factor in the event that two or more vendors are determined to be essentially equal following evaluation of the technical portion of quotations. Offerors shall also provide three references of organizations that have purchased product proposed within the past year. Offerors should also note that additional documentation requirements are contained in the evaluation criteria set below. Offerors are also notified that the Government reserves the right to make award to the vendor whose offer provides the greatest overall value to the Government. Offers will be evaluated on the following technical evaluation criteria: 1) Demonstrated use of NYCOMED contrast agents with the proposed OMRI. Use must be documented by references that have used the NYCOMED agents and have exchanged spectroscopic data and phamacologic information with NYCOMED. Such capabilities will provide NCI to assess the performance of the OMRI scanner in terms of Overhauser enhancement factors of biologically compatible contrast agents at levels below toxicity as well as acceptable RF power deposition and its suitability for tumor physiology studies. (50% weight) and 2) Demonstrated compliance with the OMRI specifications contained above (50% weight). Delivery shall shipped F.O.B. destination or F.O.B. Origin with transportation insurance (provided by the vendor) and inside delivery to the location specified within the order within six months after receipt of order. Pricing must include shipping specified previously and installation, on site training in Bethesda for three days, an initial one year warranty, with an option for a second year. Offers must be submitted on an SF-18 or SF-1449 with a completed "Schedule of Offered Supplies/Services." Offers must be accompanied by a completed "Offeror Representations and Certifications- Commercial Items -- with Duns Number Addendum," signed by an authorized representative of the offeror. Offerors must submit an original technical proposal plus descriptive literature, warranties, and/or other materials that demonstrate that their offer meets all of the foregoing requirements. In addition, four (4) copies of the technical proposal and all materials shall be submitted with the original. This solicitation incorporates the provisions at FAR 52.212-1, INSTRUCTION TO OFFERORS -- COMMERCIAL ITEMS -- DEVIATION FOR SIMPLIFIED ACQUISITIONS; FAR 52.212-2, EVALUATION -- COMMERCIAL ITEMS; FAR 52.212-3, OFFEROR REPRESENTATIONS AND CERTIFICATIONS -- COMMERCIAL ITEMS, along with the DUNS NUMBER ADDENDUM; and FAR 52.217-5 EVALUATION OF OPTIONS. The resulting contract will incorporate either acceptable Commercial Terms and Conditions of the offeror or FAR 52.212-4, CONTRACT TERMS AND CONDITIONS -- COMMERCIAL ITEMS. In addition, the resulting contract will incorporate FAR 52.212-5, CONTRACT TERMS AND CONDITIONS REQUIRED TO IMPLEMENT STATUTES OR EXECUTIVE ORDERS -- COMMERCIAL ITEMS -- DEVIATION FOR SIMPLIFIED ACQUISITIONS. The following FAR clauses cited in paragraph (b) of the clause at FAR 52.212-5 are applicable to this acquisition: FAR 52.222-26, EQUAL OPPORTUNITY; FAR 52.222-35, AFFIRMATIVE ACTION FOR DISABLED VETERANS AND VETERANS OF THE VIETNAM ERA; FAR 52.222-36, AFFIRMATIVE ACTION FOR WORKERS WITH DISABILITIES; FAR 52.222-37, EMPLOYMENT RECORDS ON DISABLED VETERANS AND VETERANS OF VIETNAM ERA; and FAR 52.225-3, BUY AMERICAN ACT -- SUPPLIES. Interested Offerors may contact Todd Cole, Contracting Officer, at (301)-402-4511 (Fax: (301)-402-4513) to receive full text copies of the representations and certifications orother cited provisions, clauses, and forms or with any questions or comments. Offers and related materials must be received in this office no later than 3:00PM EST, June 7, 1999. Please cite the solicitation number, RFQ-NCI-90109, on your offer. Posted 05/18/99 (W-SN332717). (0138)

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