Tumor-Avid 3-(1'-Hexyloxy)ethyl-3-devinylpyrpyropheophorbide-a (HPPH)-3Gd(III)tetraxetan (DOTA) Conjugate Defines Primary Tumors and Metastases.

3-(1'-Hexyloxyethyl)-3-devinylpyropheophorbide-a (HPPH or Photochlor), a tumor-avid chlorophyll a derivative currently undergoing human clinical trials, was conjugated with mono-, di-, and tri-Gd(III)tetraxetan (DOTA) moieties. The T1/T2 relaxivity and in vitro PDT efficacy of these conjugates were determined. The tumor specificity of the most promising conjugate was also investigated at various time points in mice and rats bearing colon tumors, as well as rabbits bearing widespread metastases from VX2 systemic arterial disseminated metastases. All the conjugates showed significant T1 and T2 relaxivities. However, the conjugate containing 3-Gd(III)-aminoethylamido-DOTA at position 17 of HPPH demonstrated great potential for tumor imaging by both MR and fluorescence while maintaining its PDT efficacy. At an MR imaging dose (10 µmol/kg), HPPH-3Gd(III)DOTA did not cause any significant organ toxicity in mice, indicating its potential as a cancer imaging (MR and fluorescence) agent with an option to treat cancer by photodynamic therapy (PDT).

Isolated extramedullary relapse of acute lymphoblastic leukemia in the breast of an adolescent girl: radiologic findings and discussion.

We report a case of isolated extramedullary leukemia relapse in the breast of an adolescent girl. A 13-year-old girl with acute lymphoblastic leukemia in remission, post-chemotherapy and unrelated cord blood transplant, presented with a breast lump. US and mammography demonstrated a large hypervascular heterogeneous mass. Examination of tissue provided by US-guided core biopsy confirmed focal leukemic relapse. US is a commonly used diagnostic tool in children and adolescents with a breast mass, for both characterization and guided biopsy.

Gadolinium-enhanced computed tomographic angiography: current status.

This article reviews the research to date, as well as our clinical experience from two institutions, on gadolinium-enhanced computed tomographic angiography (gCTA) for imaging the body. gCTA may be an appropriate examination for the small percentage of patients who would benefit from noninvasive vascular imaging, but who have contraindications to both iodinated contrast and magnetic resonance imaging. gCTA is more expensive than CTA with iodinated contrast, due to the dose of gadolinium administered, and gCTA has limitations compared with CTA with iodinated contrast, in that parenchymal organs are not optimally enhanced at doses of 0.5 mmol/kg or lower. However, in our experience, gCTA has been a very useful problem-solving examination in carefully selected patients. With the advent of 16-64 detector CT, in combination with bolus tracking, we believe that the overall dose of gadolinium needed for diagnostic CTA examinations, while relatively high, can be safely administered.

Chlorophyll-a analogues conjugated with aminobenzyl-DTPA as potential bifunctional agents for magnetic resonance imaging and photodynamic therapy.

A clinically relevant photosensitizer, 3-devinyl-3-(1-hexyloxyethyl)pyropheophorbide-a (HPPH, a chlorophyll-a derivative), was conjugated with Gd(III)-aminobenzyl-diethylenetriaminepentaacetic acid (DTPA), an experimental magnetic resonance (MR) imaging agent. In vivo reflectance spectroscopy confirmed tumor uptake of HPPH-aminobenzyl-Gd(III)-DTPA conjugate was higher than free HPPH administered intraveneously (iv) to C3H mice with subcutaneously (sc) implanted radiation-induced fibrosarcoma (RIF) tumor cells. In other experiments, Sprague-Dawley (SD) rats with sc implanted Ward Colon Carcinoma cells yielded markedly increased MR signal intensities from tumor regions-of-interest (ROIs) 24 h post-iv injection of HPPH-aminobenzyl-Gd(III)-DTPA conjugate as compared to unconjugated HPPH. In both in vitro (RIF tumor cells) and in vivo (mice bearing RIF tumors and rats bearing Ward Colon tumors) the conjugate produced significant increases in tumor conspicuity at 1.5 T and retained therapeutic efficacy following PDT. Also synthesized were a series of novel bifunctional agents containing two Gd(III) atoms per HPPH molecule that remained tumor-avid and PDT-active and yielded improved MR tumor conspicuity compared to their corresponding mono-Gd(III) analogues. Administered iv at a MR imaging dose of 10 micromol/kg, these conjugates produced severe skin phototoxicity. However, by replacing the hexyl group of the pyropheophorbide-a with a tri(ethylene glycol) monomethyl ether (PEG-methyl ether), these conjugates produced remarkable MR tumor enhancement at 8 h post-iv injection, significant tumoricidal activity (80% of mice were tumor-free on day 90), and reduced skin phototoxicity compared to their corresponding hexyl ether analogues. The poor water-solubility characteristic of these conjugates was resolved by incorporation into a liposomal formulation. This paper presents the synthesis of tumor-avid contrast enhancing agents for MR imaging and thus represents an important milestone toward improving cancer diagnosis and tumor characterization. More importantly, this paper describes a new family of bifunctional agents that combine two modalities into a single cost-effective "see and treat" approach, namely, a single agent that can be used for contrast agent-enhanced MR imaging followed by targeted photodynamic therapy.

CT venography in suspected pulmonary thromboembolism.

Pulmonary embolism (PE) and deep venous thrombosis (DVT) are a continuum and are difficult to diagnose clinically. Combined CT venography and pulmonary angiography (CTVPA) is a single examination that combines multidetector CT pulmonary angiography (CTPA) and CT venography (CTV) of the abdomen, pelvis, and lower extremities, providing "one-stop shopping" for venous thromboembolism without additional venipuncture or i.v. contrast, and it adds only a few additional minutes to scanning time. CTVPA rapidly and accurately examines the deep veins, reveals the presence, absence, and extent of deep venous thrombosis, serves as a baseline, and helps guide patient management. Multiple investigators have reported a high degree of accuracy when CTV is compared with venous ultrasound. There are some pitfalls in image interpretation, especially with regard to mixing artifacts, and there are continuing controversies as to exactly which parts of the abdomen, pelvis, and legs should be scanned routinely, the ideal timing of CTV acquisition relative to contrast injection, and the slice thickness and gap, if any, that should be used.

Gadopentetate dimeglumine is potentially an alternative contrast agent for three-dimensional computed tomography angiography with multidetector-row helical scanning.

OBJECTIVE: To demonstrate that gadopentetate dimeglumine is potentially an alternative contrast medium for computed tomographic angiography (CTA). METHODS: One 12.2-kg Beagle dog was studied as proof of principle; the cervical vessels of three adult human patients were imaged for presurgical planning of the neck. Gadopentetate dimeglumine, 0.5 mol/l (Berlex Laboratories, Wayne, NJ, U.S.A.), a LightSpeed QX/i CT (General Electric Medical Systems, Milwaukee, WI, U.S.A.), and an Ultra Sparc II (SUN Microsystems, Santa Clara, CA, U.S.A.) running Advantage Windows 3.1 (General Electric Medical Systems) were used. RESULTS: Sufficient enhancement for CTA of the thoracic aorta, cervical vessels, and abdominal vessels was produced in the experimental dog, and the cervical vessels were clearly defined in all three patients. CONCLUSION: In that subset of patients with contraindications to iodinated contrast medium and for whom magnetic resonance angiography is inappropriate, gadopentetate dimeglumine may be an alternative contrast medium for CTA.

Combined CT venography and pulmonary angiography: a comprehensive review.

The combination of computed tomographic (CT) venography and pulmonary angiography (CTVPA) was initially described in 1998 as a single comprehensive noninvasive imaging examination for suspected thromboembolic disease. It allowed the identification of pulmonary embolism as well as deep venous thrombosis (DVT) in the abdomen, pelvis, thighs, and calves. The venographic portion of CTVPA has now been studied by multiple researchers and has been shown to be an accurate imaging study for the thigh veins in comparison with lower extremity sonography. In contrast to sonography, however, CTVPA readily and rapidly permits evaluation of the inferior vena cava, the pelvic veins, the calf veins, and all of the superficial venous system. Complex venous anatomy can be surveyed, an additional sonographic study is not required, and only a few extra minutes and images are required over and above CT pulmonary angiography. A review of 957 recent cases of suspected pulmonary embolism examined with CTVPA revealed an overall 10.5% frequency of DVT, with a nearly equal distribution of thrombosis at the common femoral, superficial femoral, popliteal, and deep calf veins. Although a variety of protocols for CTVPA may be implemented, including a contiguous helical acquisition, obtaining 5- or 10-mm-thick images every 4 cm provides a high degree of accuracy and decreases overall radiation dose.

A Comparative Study of 511 keV SPECT and PET Using Separate 370 MBq F-18-FDG Doses on Different Days.

All previously reported comparative studies of 511 keV single-photon emission computed tomography (SPECT) and positron emission tomography (PET) have used one fluorine-18-fluorodeoxyglucose (FDG) dose, followed by PET and SPECT on the same day. This approach is inherently biased against the second imaging study. Therefore, we prospectively compared conventional PET and 511 keV SPECT in 23 patients with proven malignancy using separate 370 MBq FDG doses on different days employing an ECAT 951/31R PET scanner and a Trionix XLT-20 for SPECT. Discrepancies were evident in twelve of 23 patients (52%). In eight of these (66%) findings were seen exclusively on PET and represented the only metabolic evidence of disease. Thirty-seven of the 52 lesions (71%) detected at PET were also defined by SPECT, most above 2 cm. In 4 cases of extrahepatic abdominal disease (3 colorectal, 1 melanoma), both PET and SPECT missed small recurrent omental and perivesical lesions; several lesions up to 1.2 cm were also missed by CT and MRI.