Tomographic imaging with either F-18 fluoro deoxyglucose (FDG) (a nonmetabolizable glucose analog that reflects tumor increased glucose metabolism) or technetium Tc-99m Depreotide (a synthetic peptide that binds with high affinity to cell surface receptors with increased expression on certain tumor cells) provides improved sensitivity and specificity in the differential diagnosis of solitary pulmonary nodules (SPN) compared with noninvasive and some invasive procedures. F-18 FDG requires instrumentation capable of coincident imaging whereas Tc-99m Depreotide can be imaged on standard gamma cameras equipped to perform single photon emission computed tomography (SPECT) imaging. Either technique performs better than CT alone, and both are cost effective on the basis of reducing unnecessary biopsies and thoracotomies in patients with negative studies indicating that the SPN is nonmalignant.