RAdiolabeled Perfusion to Identify Coronary Artery Disease Using WAter To Evaluate Responses of Myocardial FLOW (RAPID-WATER-FLOW)

Inclusion Criteria:

1. Male and female participants ≥18 years;

2. Informed consent form (ICF) read, signed, and dated prior to any study proceduresbeing performed;

3. Participants who fall into any one of the following categories:

4. Have been referred for an ICA directly of after non-invasive testing (e.g.,SPECT or PET MPI, stress echo, CCTA, ETT).

5. Had an ICA with no intervention. However, if any stenosis >40% but ≤70% wasobserved, an FFR or iFR assessment was performed.

6. Had a CCTA with normal coronaries or minimal CAD (no stenosis >25%). The SPECT study, PET 15O-H2O study, and ICA or CCTA testing need to be completedwithin a 30-day window, with time 0 defined as the date of the first of these threetests.

7. Women of Child Bearing Potential (WOCBP) must be non-pregnant, and non-lactating.For women of childbearing potential, the results of a urine human chorionicgonadotropin (HCG) pregnancy test (with the result known on the day of drugadministration) must be negative; these participants must be practicing appropriatebirth control from time of the screening visit until the end of the follow-upperiod. For women who are either surgically sterile (have a documented bilateraltubal ligation or oophorectomy and/or hysterectomy) or are post-menopausal (cessation of menses for more than 1 year), enrollment in the study without apregnancy test at screening is allowed.

8. Male will need to use contraceptive methods until end of the follow-up period.

9. Participants are able to comply with all study procedures as described in theprotocol.

Exclusion Criteria:

1. Participants are unable to undergo (even partially) any of the imaging procedures;

2. Participants with a known history of cardiac disease including:

3. myocardial infarction, previous coronary revascularization, or chronic ischemiccardiomyopathy

4. primary myocardial disease such as cardiac amyloidosis or hypertrophiccardiomyopathy

5. known left ventricular dysfunction

6. moderate or severe aortic or mitral stenosis or regurgitation

7. Participants in whom adenosine stress testing is contraindicated, including but notlimited to:

8. Participants with severe COPD or chronic asthma.

9. Participants with second- or third-degree atrioventricular block without apacemaker.

10. Participants with claustrophobia to an extent that would limit their ability toundergo SPECT and PET imaging (patients whose claustrophobia is known to be readilycontrolled with drugs or psychological support may be enrolled).

11. Participants who are on sildenafil (Viagra) or oral dipyridamole (Persantine,Aggrenox) therapy or on any PDE5 inhibitor (i.e. tadalafil, avanafil,vardenafil),and for whom its use cannot be terminated or suspended for ≥24 hoursprior to treatment of study drug.

12. Participants with significant co-morbidities that would prevent appropriatecompletion of the protocol procedures.

13. Participants who have participated in another research study using investigationaldrugs within the 30 days prior to enrollment or through the duration of the trial (patients in observational studies with approved agents and participants known to beon placebo may be enrolled).

14. Participants who have previously participated in this study.

15. Subjects scheduled for, or planning to undergo, any interventional cardiacprocedures between enrollment and ICA (pathway 1) or signing of informed consent and 15O-H2O PET MPI (pathway 2 and 3)